Long-term potentiation expands information content of hippocampal dentate gyrus synapses.

PubMed

Bromer, Cailey; Bartol, Thomas M; Bowden, Jared B; Hubbard, Dusten D; Hanka, Dakota C; Gonzalez, Paola V; Kuwajima, Masaaki; Mendenhall, John M; Parker, Patrick H; Abraham, Wickliffe C; Sejnowski, Terrence J; Harris, Kristen M

2018-03-06

An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

PubMed

Han, Huili; Peng, Yan; Dong, Zhifang

2015-06-01

It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Short-Term Plasticity and Long-Term Potentiation in Magnetic Tunnel Junctions: Towards Volatile Synapses

NASA Astrophysics Data System (ADS)

Sengupta, Abhronil; Roy, Kaushik

2016-02-01

Synaptic memory is considered to be the main element responsible for learning and cognition in humans. Although traditionally nonvolatile long-term plasticity changes are implemented in nanoelectronic synapses for neuromorphic applications, recent studies in neuroscience reveal that biological synapses undergo metastable volatile strengthening followed by a long-term strengthening provided that the frequency of the input stimulus is sufficiently high. Such "memory strengthening" and "memory decay" functionalities can potentially lead to adaptive neuromorphic architectures. In this paper, we demonstrate the close resemblance of the magnetization dynamics of a magnetic tunnel junction (MTJ) to short-term plasticity and long-term potentiation observed in biological synapses. We illustrate that, in addition to the magnitude and duration of the input stimulus, the frequency of the stimulus plays a critical role in determining long-term potentiation of the MTJ. Such MTJ synaptic memory arrays can be utilized to create compact, ultrafast, and low-power intelligent neural systems.

Maintenance of long-term adaptation of synaptic transmission requires axonal transport following induction in an identified crayfish motoneuron.

PubMed

Nguyen, P V; Atwood, H L

1992-03-01

Motoneurons can adapt to altered levels of electrical activity by effecting semi-permanent changes in their neuromuscular synaptic physiology. In the present study, we tested the hypothesis that maintenance of activity-dependent long-term adaptation of synaptic transmission in a crayfish abdominal extensor motoneuron (phasic axon 3) required axonal transport following induction. Intact crayfish were chronically wired for periodic in vivo stimulation of axon 3. Periodic unilateral stimulation for 3-5 consecutive days (2 h/day) induced long-term adaptation (LTA) of neuromuscular synaptic transmission in axon 3. Initial EPSP amplitudes (measured at 0.1 Hz) were significantly reduced to approximately 40% of contralateral control amplitudes over a 7-day poststimulation period. Additionally, synaptic depression during 5 Hz test stimulation of axon 3 was significantly less in chronically stimulated neurons: excitatory postsynaptic potential (EPSP) amplitudes measured after 20 min of 5 Hz test stimulation (final EPSPs) were significantly larger in conditioned neurons than in unstimulated controls. The depression of initial EPSP amplitudes persisted for 7 days postinduction, while the increased synaptic stamina persisted for 4 days but was absent at 7 days postinduction. Axotomy of axon 3 following induction of LTA had no effect on long-term maintenance of the activity-induced reduction in initial EPSP amplitudes. Initial EPSP amplitudes in conditioned, axotomized neurons were still reduced to 42% of control amplitudes over the 7-day postinduction period. In contrast, postinduction axotomy of axon 3 elicited an accelerated decay of the enhanced synaptic stamina. Following axotomy, final EPSP amplitudes were significantly larger in conditioned neurons for only 1 day poststimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Pettorossi, V E; Grassi, S

2001-01-01

In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

Impairment of long-term potentiation induction is essential for the disruption of spatial memory after microwave exposure.

PubMed

Wang, Hui; Peng, Ruiyun; Zhou, Hongmei; Wang, Shuiming; Gao, Yabing; Wang, Lifeng; Yong, Zheng; Zuo, Hongyan; Zhao, Li; Dong, Ji; Xu, Xinping; Su, Zhentao

2013-12-01

To assess the impact of microwave exposure on learning and memory and to explore the underlying mechanisms. 100 Wistar rats were exposed to a 2.856 GHz pulsed microwave field at average power densities of 0 mW/cm(2), 5 mW/cm(2), 10 mW/cm(2) and 50 mW/cm(2) for 6 min. The spatial memory was assessed by the Morris Water Maze (MWM) task. An in vivo study was conducted soon after microwave exposure to evaluate the changes of population spike (PS) amplitudes of long-term potentiation (LTP) in the medial perforant path (MPP)-dentate gyrus (DG) pathway. The structure of the hippocampus was observed by the light microscopy and the transmission electron microscopy (TEM) at 7 d after microwave exposure. Our results showed that the rats exposed in 10 mW/cm(2) and 50 mW/cm(2) microwave displayed significant deficits in spatial learning and memory at 6 h, 1 d and 3 d after exposure. Decreased PS amplitudes were also found after 10 mW/cm(2) and 50 mW/cm(2) microwave exposure. In addition, varying degrees of degeneration of hippocampal neurons, decreased synaptic vesicles and blurred synaptic clefts were observed in the rats exposed in 10 mW/cm(2) and 50 mW/cm(2) microwave. Compared with the sham group, the rats exposed in 5 mW/cm(2) microwave showed no difference in the above experiments. This study suggested that impairment of LTP induction and the damages of hippocampal structure, especially changes of synapses, might contribute to cognitive impairment after microwave exposure.

Platelet-activating factor and group I metabotropic glutamate receptors interact for full development and maintenance of long-term potentiation in the rat medial vestibular nuclei.

PubMed

Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

1999-01-01

In rat brainstem slices, we investigated the interaction between platelet-activating factor and group I metabotropic glutamate receptors in mediating long-term potentiation within the medial vestibular nuclei. We analysed the N1 field potential wave evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation. The group I metabotropic glutamate receptor antagonist, (R,S)-1-aminoindan-1,5-dicarboxylic acid, prevented long-term potentiation induced by a platelet-activating factor analogue [1-O-hexadecyl-2-O-(methylcarbamyl)-sn-glycero-3-phosphocholine], as well as the full development of potentiation, induced by high-frequency stimulation under the blocking agent for synaptosomal platelet-activating factor receptors (ginkolide B), at drug washout. However, potentiation directly induced by the group I glutamate metabotropic receptor agonist, (R,S)-3,5-dihydroxyphenylglycine, was reduced by ginkolide B. These findings suggest that platelet-activating factor, whether exogenous or released following potentiation induction, exerts its effect through presynaptic group I metabotropic glutamate receptors, mediating the increase of glutamate release. In addition, we found that this mechanism, which led to full potentiation through presynaptic group I metabotropic glutamate receptor activation, was inactivated soon after application of potentiation-inducing stimulus. In fact, the long-lasting block of the platelet-activating factor and metabotropic glutamate receptors prevented the full potentiation development and the induced potentiation progressively declined to null. Moreover, ginkolide B, given when high-frequency-dependent potentiation was established, only reduced it within 5 min after potentiation induction. We conclude that to fully develop vestibular long-term potentiation requires presynaptic events. Platelet-activating factor, released after the activation of postsynaptic mechanisms which induce potentiation, is necessary

Shifting patterns of polyribosome accumulation at synapses over the course of hippocampal long-term potentiation.

PubMed

Ostroff, Linnaea E; Watson, Deborah J; Cao, Guan; Parker, Patrick H; Smith, Heather; Harris, Kristen M

2018-06-01

Hippocampal long-term potentiation (LTP) is a cellular memory mechanism. For LTP to endure, new protein synthesis is required immediately after induction and some of these proteins must be delivered to specific, presumably potentiated, synapses. Local synthesis in dendrites could rapidly provide new proteins to synapses, but the spatial distribution of translation following induction of LTP is not known. Here, we quantified polyribosomes, the sites of local protein synthesis, in CA1 stratum radiatum dendrites and spines from postnatal day 15 rats. Hippocampal slices were rapidly fixed at 5, 30, or 120 min after LTP induction by theta-burst stimulation (TBS). Dendrites were reconstructed through serial section electron microscopy from comparable regions near the TBS or control electrodes in the same slice, and in unstimulated hippocampus that was perfusion-fixed in vivo. At 5 min after induction of LTP, polyribosomes were elevated in dendritic shafts and spines, especially near spine bases and in spine heads. At 30 min, polyribosomes remained elevated only in spine bases. At 120 min, both spine bases and spine necks had elevated polyribosomes. Polyribosomes accumulated in spines with larger synapses at 5 and 30 min, but not at 120 min. Small spines, meanwhile, proliferated dramatically by 120 min, but these largely lacked polyribosomes. The number of ribosomes per polyribosome is variable and may reflect differences in translation regulation. In dendritic spines, but not shafts, there were fewer ribosomes per polyribosome in the slice conditions relative to in vivo, but this recovered transiently in the 5 min LTP condition. Overall, our data show that LTP induces a rapid, transient upregulation of large polyribosomes in larger spines, and a persistent upregulation of small polyribosomes in the bases and necks of small spines. This is consistent with local translation supporting enlargement of potentiated synapses within minutes of LTP induction. © 2018 Wiley

Astrocyte-neuron lactate transport is required for long-term memory formation.

PubMed

Suzuki, Akinobu; Stern, Sarah A; Bozdagi, Ozlem; Huntley, George W; Walker, Ruth H; Magistretti, Pierre J; Alberini, Cristina M

2011-03-04

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Astrocyte-neuron lactate transport is required for long-term memory formation

PubMed Central

Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Walker, Ruth H.; Magistretti, Pierre J.; Alberini, Cristina M.

2011-01-01

SUMMARY We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in-vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. PMID:21376239

Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

PubMed Central

Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

2015-01-01

Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

PubMed Central

2011-01-01

Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents. PMID:21443797

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

DEVELOPMENTAL LEAD (PB) EXPOSURE REDUCES THE ABILITY OF THE NNDA ANTAGONIST MK801 TO SUPPRESS LONG-TERM POTENTIATION (LTP) IN THE RAT DENTATE GYRUS, IN VIVO

EPA Science Inventory

Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LT...

Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

PubMed

Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

2018-05-01

Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

PubMed

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2011-01-01

A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

1998-06-01

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

PubMed

Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

2006-10-01

Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

Long term potentiation depends on release of D-serine from astrocytes

PubMed Central

Henneberger, Christian; Papouin, Thomas; Oliet, Stéphane H. R.; Rusakov, Dmitri A.

2009-01-01

Long-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory1. The classical form of LTP relies on N-methyl-D-aspartate receptors (NMDARs), and it has emerged that astroglia can regulate their activation through Ca2+-dependent release of the NMDAR co-agonist D-serine2-4. Release of D-serine from glia enables LTP in cultures5 and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus4. However, Ca2+ elevations in astroglia can also release other signalling molecules, most prominently glutamate6-8, Adenosine-5′-triphosphate9, and Tumor-Necrosis-Factor-α10,11 whereas neurons themselves can synthesise and supply D-serine12,13. Furthermore, loading an astrocyte with exogenous Ca2+ buffers does not suppress LTP in hippocampal area CA114-16, and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned17,18. The involvement of glia in LTP induction thus remains controversial. Here we show that clamping internal Ca2+ in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by reducing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous D-serine or glycine whereas depletion of D-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We thus demonstrate that Ca2+-dependent release of D-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses occurring nearby. PMID:20075918

A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit.

PubMed

Świetlik, D; Białowąs, J; Kusiak, A; Cichońska, D

2018-01-01

An experimental study of computational model of the CA3 region presents cog-nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = -0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210-220).

Postsynaptic N-type or P/Q-type calcium channels mediate long-term potentiation by group I metabotropic glutamate receptors in the trigeminal oralis.

PubMed

Weon, Haein; Kim, Tae Wan; Youn, Dong-Ho

2017-11-01

Both N-type and P/Q-type voltage-gated Ca 2+ channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs). (S)-3,5-Dihydroxyphenylglycine (DHPG; 10μM for 5min), the group I mGluR agonist, was used to induce LTP of excitatory postsynaptic currents that were evoked in the Vo neurons by stimulating the trigeminal track. Weak blockade of the N-type or P/Q-type VGCCs by ω-conotoxin GVIA or ω-agatoxin IVA, respectively, which inhibited only 20-40% of Ca 2+ currents recorded in isolated trigeminal ganglion neurons but had no effect on the basal excitatory synaptic transmission, completely blocked the induction of LTP. In contrast, stronger blockade of the channels, which inhibited >50% of Ca 2+ currents and about 30% of basal synaptic transmission, resulted in the development of long-term depression (LTD), the long-lasting decrease of synaptic strength. Interestingly, the postsynaptic mechanism of DHPG-induced LTP, which was determined by paired-pulse ratio, disappeared when LTP was blocked, or LTD occurred, while a presynaptic mechanism still remained. Our data suggest that postsynaptic N-type and P/Q-type VGCCs mediate the DHPG-induced LTP at the trigeminal afferent synapses in the Vo. Copyright © 2017 Elsevier Inc. All rights reserved.

The discovery of long-term potentiation.

PubMed

Lømo, Terje

2003-04-29

This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.

The discovery of long-term potentiation.

PubMed Central

Lømo, Terje

2003-01-01

This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP. PMID:12740104

Neurogranin restores amyloid β-mediated synaptic transmission and long-term potentiation deficits.

PubMed

Kaleka, Kanwardeep Singh; Gerges, Nashaat Z

2016-03-01

Amyloid β (Aβ) is widely considered one of the early causes of cognitive deficits observed in Alzheimer's disease. Many of the deficits caused by Aβ are attributed to its disruption of synaptic function represented by its blockade of long-term potentiation (LTP) and its induction of synaptic depression. Identifying pathways that reverse these synaptic deficits may open the door to new therapeutic targets. In this study, we explored the possibility that Neurogranin (Ng)-a postsynaptic calmodulin (CaM) targeting protein that enhances synaptic function-may rescue Aβ-mediated deficits in synaptic function. Our results show that Ng is able to reverse synaptic depression and LTP deficits induced by Aβ. Furthermore, Ng's restoration of synaptic transmission is through the insertion of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs). These restorative effects of Ng are dependent on the interaction of Ng and CaM and CaM-dependent activation of CaMKII. Overall, this study identifies a novel mechanism to rescue synaptic deficits induced by Aβ oligomers. It also suggests Ng and CaM signaling as potential therapeutic targets for Alzheimer's disease as well as important tools to further explore the pathophysiology underlying the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.

PubMed

Costa, Rui Ponte; Padamsey, Zahid; D'Amour, James A; Emptage, Nigel J; Froemke, Robert C; Vogels, Tim P

2017-09-27

Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Heterosynaptic changes accompany long-term but not short-term potentiation of the perforant path in the anaesthetized rat.

PubMed

Abraham, W C; Bliss, T V; Goddard, G V

1985-06-01

Brief high-frequency trains of electrical stimulation delivered to the perforant path result in long-term potentiation (l.t.p.) of field potentials recorded extracellularly from granule cells of the dentate gyrus. L.t.p. of the population spike is often disproportionately greater than l.t.p. of the population excitatory post-synaptic potential (e.p.s.p.). We have investigated the basis of this effect in rats anaesthetized with sodium pentobarbitone. A series of graded stimuli were given before and after tetanization of the perforant path. From data obtained in this way, we plotted stimulus-response curves, and the relation (E-S curve) between the slope of the population e.p.s.p. (E) and the amplitude of the population spike (S). Curves relating spike onset latency to the slope of the e.p.s.p. were also constructed. Tetanization of the combined medial and lateral components of the perforant path led to long-term changes in the relation between the e.p.s.p. and the population spike. For a given e.p.s.p., the corresponding population spike was of greater amplitude and earlier onset. This E-S potentiation was marked by a shift to the left of the E-S amplitude curve and a downward displacement of the E-S latency curve. Tetanization of the lateral component of the perforant path had two long-term effects on responses evoked by test stimuli to the untetanized medial component: (1) long-term depression of the medial e.p.s.p. and (2) long-term E-S potentiation. The net result of these two heterosynaptically induced effects was to leave unaltered information transfer across medial perforant path-granule cell synapses; for a given test volley the e.p.s.p. was smaller, but because of E-S potentiation the population spike remained relatively unaffected. Short-term potentiation, which has a time course of only a few minutes and is presumed to be mediated by presynaptic mechanisms, was not accompanied by E-S potentiation or by corresponding changes in spike latency. Possible

Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor.

PubMed

Rex, Christopher S; Lauterborn, Julie C; Lin, Ching-Yi; Kramár, Eniko A; Rogers, Gary A; Gall, Christine M; Lynch, Gary

2006-08-01

Restoration of neuronal viability and synaptic plasticity through increased trophic support is widely regarded as a potential therapy for the cognitive declines that characterize aging. Previous studies have shown that in the hippocampal CA1 basal dendritic field deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested whether increasing endogenous brain-derived neurotrophic factor (BDNF) could reverse this age-related change. We report here that in middle-aged (8- to 10-mo-old) rats, in vivo treatments with a positive AMPA-type glutamate receptor modulator both increase BDNF protein levels in the cortical telencephalon and restore stabilization of basal dendritic LTP as assessed in acute hippocampal slices 18 h after the last drug treatment. These effects were not attributed to enhanced synaptic transmission or to facilitation of burst responses used to induce LTP. Increasing extracellular levels of BDNF by exogenous application to slices of middle-aged rats was also sufficient to rescue the stabilization of basal dendritic LTP. Finally, otherwise stable LTP in ampakine-treated middle-aged rats can be eliminated by infusion of the extracellular BDNF scavenger TrkB-Fc. Together these results indicate that increases in endogenous BDNF signaling can offset deficits in the postinduction processes that stabilize LTP.

Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.

PubMed

Ryan, Benedict K; Vollmayr, Barbara; Klyubin, Igor; Gass, Peter; Rowan, Michael J

2010-06-01

The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (<3 h), inhibited induction of both NMDA receptor-dependent LTP induced by a standard high frequency (200 Hz) conditioning stimulus and an additional LTP that required voltage-dependent Ca(2+) channel activation triggered by strong (400 Hz) conditioning stimulation. In contrast, acute inescapable footshock stress, used to study learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

PubMed Central

Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

2006-01-01

Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders. PMID:17050681

Hippocampal CA1 Kindling but Not Long-Term Potentiation Disrupts Spatial Memory Performance

ERIC Educational Resources Information Center

Leung, L. Stan; Shen, Bixia

2006-01-01

Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied…

NMDA receptor-mediated long term modulation of electrically evoked field potentials in the rat medial vestibular nuclei.

PubMed

Capocchi, G; Della Torre, G; Grassi, S; Pettorossi, V E; Zampolini, M

1992-01-01

The effect of high frequency stimulation (HFS) of the primary vestibular afferents on field potentials recorded in the ipsilateral Medial Vestibular Nuclei (MVN) was studied. Our results show that potentiation and depression can be induced in different portions of MVN, which are distinguishable by their anatomical organization. HFS induces potentiation of the monosynaptic component in the ventral portion of the MVN, whereas it provokes depression of the polysynaptic component in the dorsal portion of the same nucleus. The induction of both potentiation and depression was blocked under AP5 perfusion, thus demonstrating that NMDA receptor activation mediates both phenomena. Furthermore, the finding that the field potentials were not modified during perfusion with DL-AP5, as previously reported, supports the hypothesis that NMDA receptors are not involved in the normal synaptic transmission from the primary vestibular afferent fibres, but are only activated following hyperstimulation of this afferent system. Our results suggest that the mechanisms of long term modification of synaptic efficacy observed in MVN may underlie the plasticity phenomena occurring in vestibular nuclei.

Long-Term Economic Benefits of Preschool Services and the Potential Impact of Privatization.

ERIC Educational Resources Information Center

Kendall, Earline D.

This paper addresses the importance of a high quality preschool education for children living in poverty, the long-term effects of such an educational experience, the long-term economic benefits to the children enrolled and their families, and the potential impact of privatization on preschool services. The cost-effectiveness and cost-benefits of…

Dissecting the Components of Long-Term Potentiation

PubMed Central

Blundon, Jay A.; Zakharenko, Stanislav S.

2009-01-01

The formation of memories relies on plastic changes at synapses between neurons. Although the mechanisms of synaptic plasticity have been studied extensively over several decades, many aspects of this process remain controversial. The cellular locus of expression of long-term potentiation (LTP), a major form of synaptic plasticity, is one of the most important unresolved phenomena. In this article, we summarize some recent advances in this area made possible by the development of new imaging tools. These studies have demonstrated that LTP is compound in nature and consists of both presynaptic and postsynaptic components. We also review some features of presynaptic and postsynaptic changes during compound LTP. PMID:18940785

SGK Protein Kinase Facilitates the Expression of Long-Term Potentiation in Hippocampal Neurons

ERIC Educational Resources Information Center

Ma, Yun L.; Tsai, Ming C.; Hsu, Wei L.; Lee, Eminy H.Y.

2006-01-01

Previous studies showed that the serum- and glucocorticoid-inducible kinase ("sgk") gene plays an important role in long-term memory formation. The present study further examined the role of SGK in long-term potentiation (LTP). The dominant-negative mutant of "sgk," SGKS422A, was used to inactivate SGK. Results revealed a time-dependent increase…

Synapse Specificity of Long-Term Potentiation Breaks Down with Aging

ERIC Educational Resources Information Center

Ris, Laurence; Godaux, Emile

2007-01-01

Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long-term potentiation (LTP). Here,…

Temporal profiling of gene networks associated with the late phase of long-term potentiation in vivo.

PubMed

Ryan, Margaret M; Ryan, Brigid; Kyrke-Smith, Madeleine; Logan, Barbara; Tate, Warren P; Abraham, Wickliffe C; Williams, Joanna M

2012-01-01

Long-term potentiation (LTP) is widely accepted as a cellular mechanism underlying memory processes. It is well established that LTP persistence is strongly dependent on activation of constitutive and inducible transcription factors, but there is limited information regarding the downstream gene networks and controlling elements that coalesce to stabilise LTP. To identify these gene networks, we used Affymetrix RAT230.2 microarrays to detect genes regulated 5 h and 24 h (n = 5) after LTP induction at perforant path synapses in the dentate gyrus of awake adult rats. The functional relationships of the differentially expressed genes were examined using DAVID and Ingenuity Pathway Analysis, and compared with our previous data derived 20 min post-LTP induction in vivo. This analysis showed that LTP-related genes are predominantly upregulated at 5 h but that there is pronounced downregulation of gene expression at 24 h after LTP induction. Analysis of the structure of the networks and canonical pathways predicted a regulation of calcium dynamics via G-protein coupled receptors, dendritogenesis and neurogenesis at the 5 h time-point. By 24 h neurotrophin-NFKB driven pathways of neuronal growth were identified. The temporal shift in gene expression appears to be mediated by regulation of protein synthesis, ubiquitination and time-dependent regulation of specific microRNA and histone deacetylase expression. Together this programme of genomic responses, marked by both homeostatic and growth pathways, is likely to be critical for the consolidation of LTP in vivo.

Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation

PubMed Central

Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W.; Taylor, Denise; Haavik, Heidi; Niazi, Imran K.

2015-01-01

Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement. PMID:26648859

Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation.

PubMed

Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W; Taylor, Denise; Haavik, Heidi; Niazi, Imran K

2015-01-01

Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement.

Protective Effects of Enriched Environment Against Transient Cerebral Ischemia-Induced Impairment of Passive Avoidance Memory and Long-Term Potentiation in Rats

PubMed Central

Ahmadalipour, Ali; Sadeghzadeh, Jafar; Samaei, Seyed Afshin; Rashidy-Pour, Ali

2017-01-01

Introduction: Enriched Environment (EE), a complex novel environment, has been demonstrated to improve synaptic plasticity in both injured and intact animals. The present study investigated the capacity of an early environmental intervention to normalize the impairment of passive avoidance memory and Long-Term Potentiation (LTP) induced by transient bilateral common carotid artery occlusion (2-vessel occlusion, 2VO) in rats. Methods: After weaning, young Wistar rats (22 days old) were housed in EE or Standard Environment (SE) for 40 days. Transient (30-min) incomplete forebrain ischemia was induced 4 days before the passive avoidance memory test and LTP induction. Results: The transient forebrain ischemia led to impairment of passive avoidance memory and LTP induction in the Perforant Path-Dentate Gyrus (PP-DG) synapses. Interestingly, housing and growing in EE prior to 2VO was found to significantly reverse 2VO-induced cognitive and LTP impairments. Conclusion: Our results suggest that early housing and growing in EE exhibits therapeutic potential to normalize cognitive and LTP abnormalities induced by 2VO ischemic model in rats.

Ionotropic NMDA receptor signaling is required for the induction of long-term depression in the mouse hippocampal CA1 region.

PubMed

Babiec, Walter E; Guglietta, Ryan; Jami, Shekib A; Morishita, Wade; Malenka, Robert C; O'Dell, Thomas J

2014-04-09

Previous studies have provided strong support for the notion that NMDAR-mediated increases in postsynaptic Ca(2+) have a crucial role in the induction of long-term depression (LTD). This view has recently been challenged, however, by findings suggesting that LTD induction is instead attributable to an ion channel-independent, metabotropic form of NMDAR signaling. Thus, to explore the role of ionotropic versus metabotropic NMDAR signaling in LTD, we examined the effects of varying extracellular Ca(2+) levels or blocking NMDAR channel ion fluxes with MK-801 on LTD and NMDAR signaling in the mouse hippocampal CA1 region. We find that the induction of LTD in the adult hippocampus is highly sensitive to extracellular Ca(2+) levels and that MK-801 blocks NMDAR-dependent LTD in the hippocampus of both adult and immature mice. Moreover, MK-801 inhibits NMDAR-mediated activation of p38-MAPK and dephosphorylation of AMPAR GluA1 subunits at sites implicated in LTD. Thus, our results indicate that the induction of LTD in the hippocampal CA1 region is dependent on ionotropic, rather than metabotropic, NMDAR signaling.

Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso–ventral Axis

PubMed Central

Nishijima, Takeshi; Kawakami, Masashi; Kita, Ichiro

2013-01-01

Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso–ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

PubMed

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

PubMed Central

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-01-01

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice. DOI: http://dx.doi.org/10.7554/eLife.14846.001 PMID:27187150

Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

PubMed Central

Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

2015-01-01

17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease. PMID:26074768

Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system.

PubMed

Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

2015-01-01

17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

Long Latency Auditory Evoked Potential in Term and Premature Infants

PubMed Central

Didoné, Dayane Domeneghini; Garcia, Michele Vargas; da Silveira, Aron Ferreira

2013-01-01

Introduction The research in long latency auditory evokes potentials (LLAEP) in newborns is recent because of the cortical structure maturation, but studies note that these potentials may be evidenced at this age and could be considered as indicators of cognitive development. Purpose To research the exogenous potentials in term and premature infants during their first month of life. Materials and Methods The sample consisted of 25 newborns, 15 term and 10 premature infants. The infants with gestational age under 37 weeks were considered premature. To evaluate the cortical potentials, the infants remained in natural sleep. The LLAEPs were researched binaurally, through insertion earphones, with frequent /ba/ and rare /ga/ speech stimuli in the intensity of 80 dB HL (decibel hearing level). The frequent stimuli presented a total of 80% of the presentations, and the rare, 20%. The data were statistically analyzed. Results The average gestational age of the term infants was 38.9 weeks (± 1.3) and for the premature group, 33.9 weeks (± 1.6). It was possible to observe only the potentials P1 and N1 in both groups, but there was no statistically significant difference for the latencies of the components P1 and N1 (p > 0.05) between the groups. Conclusion It was possible to observe the exogenous components P1 and N1 of the cortical potentials in both term and preterm newborns of no more than 1 month of age. However, there was no difference between the groups. PMID:25992057

Potential breeding distributions of U.S. birds predicted with both short-term variability and long-term average climate data.

PubMed

Bateman, Brooke L; Pidgeon, Anna M; Radeloff, Volker C; Flather, Curtis H; VanDerWal, Jeremy; Akçakaya, H Resit; Thogmartin, Wayne E; Albright, Thomas P; Vavrus, Stephen J; Heglund, Patricia J

2016-12-01

Climate conditions, such as temperature or precipitation, averaged over several decades strongly affect species distributions, as evidenced by experimental results and a plethora of models demonstrating statistical relations between species occurrences and long-term climate averages. However, long-term averages can conceal climate changes that have occurred in recent decades and may not capture actual species occurrence well because the distributions of species, especially at the edges of their range, are typically dynamic and may respond strongly to short-term climate variability. Our goal here was to test whether bird occurrence models can be predicted by either covariates based on short-term climate variability or on long-term climate averages. We parameterized species distribution models (SDMs) based on either short-term variability or long-term average climate covariates for 320 bird species in the conterminous USA and tested whether any life-history trait-based guilds were particularly sensitive to short-term conditions. Models including short-term climate variability performed well based on their cross-validated area-under-the-curve AUC score (0.85), as did models based on long-term climate averages (0.84). Similarly, both models performed well compared to independent presence/absence data from the North American Breeding Bird Survey (independent AUC of 0.89 and 0.90, respectively). However, models based on short-term variability covariates more accurately classified true absences for most species (73% of true absences classified within the lowest quarter of environmental suitability vs. 68%). In addition, they have the advantage that they can reveal the dynamic relationship between species and their environment because they capture the spatial fluctuations of species potential breeding distributions. With this information, we can identify which species and guilds are sensitive to climate variability, identify sites of high conservation value where climate

High-frequency stimulation of the temporoammonic pathway induces input-specific long-term potentiation in subicular bursting cells.

PubMed

Fidzinski, Pawel; Wawra, Matthias; Bartsch, Julia; Heinemann, Uwe; Behr, Joachim

2012-01-09

The subiculum (Sub) as a part of the hippocampal formation is thought to play a functional role in learning and memory. In addition to its major input from CA1 pyramidal cells, the subiculum receives input from the entorhinal cortex (EC) via the temporoammonic pathway. Thus far, synaptic plasticity in the subiculum was mainly investigated at CA1-Sub synapses. According to their spiking pattern, pyramidal cells in the subiculum were classified as bursting cells and non-bursting cells. In the present study, we demonstrate that subicular bursting cells show input-specific forms of long-term potentiation (LTP). At CA1-Sub synapses, bursting cells have been shown to express a presynaptic NMDA receptor-dependent LTP that depends on the activation of a cAMP-PKA cascade (Wozny et al., Journal of Physiology 2008). In contrast, at EC-Sub synapses the induction of LTP in bursting cells shows a high induction-threshold and relies on the activation of postsynaptic NMDA receptors, postsynaptic depolarization and postsynaptic Ca(2+) influx. Each form of LTP is input-specific and fails to induce heterosynaptic plasticity. Taken together, our data suggest that distinct, input-specific mechanisms govern high frequency-induced LTP at subicular bursting cells' synapses. Copyright © 2011 Elsevier B.V. All rights reserved.

Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

PubMed

Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A

2013-07-26

RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.

Acquisition of Contextual Discrimination Involves the Appearance of a RAS-GRF1/p38 Mitogen-activated Protein (MAP) Kinase-mediated Signaling Pathway That Promotes Long Term Potentiation (LTP)*

PubMed Central

Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A.

2013-01-01

RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway. PMID:23766509

Long-term potentiation in the rat medial vestibular nuclei depends on locally synthesized 17beta-estradiol.

PubMed

Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Scarduzio, Mariangela; Pettorossi, Vito E

2009-08-26

In male rat brainstem slices, we investigated the involvement of locally synthesized 17beta-estradiol (E(2)) in the induction in the medial vestibular nucleus (MVN) of long-term potentiation (LTP) by high-frequency stimulation (HFS) of the primary vestibular afferents. We demonstrated that the blockade of aromatase by letrozole or of E(2) receptors (ERalpha and ERbeta) by ICI 182,780 prevented the HFS-induced LTP of the N1 wave of the evoked field potential (FP) without affecting baseline responses. Only prolonged afferent activation could induce low LTP. In contrast, HFS applied under a combined blockade of GABA(A) receptors and aromatase or ERs was still able to induce LTP, but it was significantly lower and slower. These findings demonstrate that E(2) does not have a tonic influence on the activity of the MVN neurons and provide the first evidence of the crucial role played by local synthesis of E(2) in inducing LTP. We suggest that the synthesis of E(2) occurs after aromatase activation during HFS and facilitates the development of vestibular synaptic plasticity by influencing glutamate and GABA transmission.

Long-term potentiation of synaptic response and intrinsic excitability in neurons of the rat medial vestibular nuclei.

PubMed

Pettorossi, V E; Dieni, C V; Scarduzio, M; Grassi, S

2011-07-28

Using intracellular recordings, we investigated the effects of high frequency stimulation (HFS) of the primary vestibular afferents on the evoked excitatory postsynaptic potential (EPSP) and intrinsic excitability (IE) of type-A and type-B neurons of the medial vestibular nucleus (MVN), in male rat brainstem slices. HFS induces long-term potentiation (LTP) of both EPSP and IE, which may occur in combination or separately. Synaptic LTP is characterized by an increase in the amplitude, slope and decay time constant of EPSP and IE-LTP through enhancements of spontaneous and evoked neuron firing and of input resistance (Rin). Moreover, IE-LTP is associated with a decrease in action potential afterhyperpolarization (AHP) amplitude and an increase in interspike slope steepness (ISS). The more frequent effects of HFS are EPSP-LTP in type-B neurons and IE-LTP in type-A neurons. In addition, the development of EPSP-LTP is fast in type-B neurons but slow in type-A, whereas IE-LTP develops slowly in both types. We have demonstrated that activation of N-methyl-d aspartate receptors (NMDARs) is only required for EPSP-LTP induction, whereas metabotropic glutamate receptors type-1 (mGluR1) are necessary for IE-LTP induction as well as the full development and maintenance of EPSP-LTP. Taken together, these findings demonstrate that brief and intense activation of vestibular afferent input to the MVN neurons may provoke synaptic LTP and/or IE-LTP that, induced in combination or separately, may assure the different selectivity of the MVN neuron response enhancement to the afferent signals. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation induced by forskolin.

PubMed

Ando, Masaki; Oku, Naoto; Takeda, Atsushi

2010-11-01

The rise in presynaptic calcium induced by high-frequency stimulation activates the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the induction of long-term potentiation (LTP) at the hippocampal mossy fiber-CA3 synapse. Zinc is released with glutamate from mossy fiber terminals. However, the role of the zinc in mossy fiber LTP is controversial. In the present study, the mechanism of zinc-mediated attenuation of mossy fiber LTP was examined in that induced by forskolin, an AC activator. Mossy fiber LTP induced by tetanic stimulation (100 Hz for 1 s) was attenuated in the presence of 5 microM ZnCl(2), whereas that induced by forskolin under test stimulation (0.1 Hz) was not attenuated. Forskolin-induced mossy fiber LTP was attenuated by perfusion with 100 microM ZnCl(2) prior to the induction. However, the zinc (100 microM) pre-perfusion did not attenuate mossy fiber LTP induced by Sp-cAMPS, an activator of protein kinase A, under test stimulation. Zinc is necessary to be taken up into mossy fiber boutons for effectively inhibiting AC activity. In hippocampal slices labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2 signal was increased during tetanic stimulation in the presence of 5 microM ZnCl(2), but not under test stimulation. Intracellular ZnAF-2 signal was increased under test stimulation in the presence of 100 microM ZnCl(2). These results suggest that zinc taken up into mossy fibers attenuates forskolin-induced mossy fiber LTP via inhibition of AC activity. The significance of endogenous zinc uptake by mossy fibers is discussed focused on tetanus-induced mossy fiber LTP. Copyright 2010 Elsevier Ltd. All rights reserved.

Multiple receptors coupled to phospholipase C gate long-term depression in visual cortex.

PubMed

Choi, Se-Young; Chang, Jeff; Jiang, Bin; Seol, Geun-Hee; Min, Sun-Seek; Han, Jung-Soo; Shin, Hee-Sup; Gallagher, Michela; Kirkwood, Alfredo

2005-12-07

Long-term depression (LTD) in sensory cortices depends on the activation of NMDA receptors. Here, we report that in visual cortical slices, the induction of LTD (but not long-term potentiation) also requires the activation of receptors coupled to the phospholipase C (PLC) pathway. Using immunolesions in combination with agonists and antagonists, we selectively manipulated the activation of alpha1 adrenergic, M1 muscarinic, and mGluR5 glutamatergic receptors. Inactivation of these PLC-coupled receptors prevents the induction of LTD, but only when the three receptors were inactivated together. LTD is fully restored by activating any one of them or by supplying intracellular D-myo-inositol-1,4,5-triphosphate (IP3). LTD was also impaired by intracellular application of PLC or IP3 receptor blockers, and it was absent in mice lacking PLCbeta1, the predominant PLC isoform in the forebrain. We propose that visual cortical LTD requires a minimum of PLC activity that can be supplied independently by at least three neurotransmitter systems. This essential requirement places PLC-linked receptors in a unique position to control the induction of LTD and provides a mechanism for gating visual cortical plasticity via extra-retinal inputs in the intact organism.

Pharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased Synapses

PubMed Central

Berchtold, Nicole C.; Lynch, Gary; Cotman, Carl W.

2017-01-01

Long-term potentiation (LTP) is an activity-dependent and persistent increase in synaptic transmission. Currently available techniques to measure LTP are time-intensive and require highly specialized expertise and equipment, and thus are not well suited for screening of multiple candidate treatments, even in animal models. To expand and facilitate the analysis of LTP, here we use a flow cytometry-based method to track chemically induced LTP by detecting surface AMPA receptors in isolated synaptosomes: fluorescence analysis of single-synapse long-term potentiation (FASS-LTP). First, we demonstrate that FASS-LTP is simple, sensitive, and models electrically induced LTP recorded in intact circuitries. Second, we conducted FASS-LTP analysis in two well-characterized Alzheimer's disease (AD) mouse models (3xTg and Tg2576) and, importantly, in cryopreserved human AD brain samples. By profiling hundreds of synaptosomes, our data provide the first direct evidence to support the idea that synapses from AD brain are intrinsically defective in LTP. Third, we used FASS-LTP for drug evaluation in human synaptosomes. Testing a panel of modulators of cAMP and cGMP signaling pathways, FASS-LTP identified vardenafil and Bay-73–6691 (phosphodiesterase-5 and -9 inhibitors, respectively) as potent enhancers of LTP in synaptosomes from AD cases. These results indicate that our approach could provide the basis for protocols to study LTP in both healthy and diseased human brains, a previously unattainable goal. SIGNIFICANCE STATEMENT Learning and memory depend on the ability of synapses to strengthen in response to activity. Long-term potentiation (LTP) is a rapid and persistent increase in synaptic transmission that is thought to be affected in Alzheimer's disease (AD). However, direct evidence of LTP deficits in human AD brain has been elusive, primarily due to methodological limitations. Here, we analyze LTP in isolated synapses from AD brain using a novel approach that allows

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. Copyright © 2016 Elsevier B.V. All rights reserved.

LTP Induction Modifies Functional Relationship among Hippocampal Neurons

ERIC Educational Resources Information Center

Yun, Sung H.; Lee, Deok S.; Lee, Hyunjung; Baeg, Eun H.; Kim, Yun B.; Jung, Min W.

2007-01-01

To obtain evidence linking long-term potentiation (LTP) and memory, we examined whether LTP induction modifies functional relationship among neurons in the rat hippocampus. In contrast to neurons in low-frequency stimulated or AP5-treated slices, LTP induction altered "functional connectivity," as defined by the degree of synchronous firing, among…

Long-term effect of set potential on biocathodes in microbial fuel cells: electrochemical and phylogenetic characterization.

PubMed

Xia, Xue; Sun, Yanmei; Liang, Peng; Huang, Xia

2012-09-01

The long-term effect of set potential on oxygen reducing biocathodes was investigated in terms of electrochemical and biological characteristics. Three biocathodes were poised at 200, 60 and -100 mV vs. saturated calomel electrode (SCE) for 110 days, including the first 17 days for startup. Electrochemical analyses showed that 60 mV was the optimum potential during long-term operation. The performance of all the biocathodes kept increasing after startup, suggesting a period longer than startup time needed to make potential regulation more effective. The inherent characteristics without oxygen transfer limitation were studied. Different from short-term regulation, the amounts of biomass were similar while the specific electrochemical activity was significantly influenced by potential. Moreover, potential showed a strong selection for cathode bacteria. Clones 98% similar with an uncultured Bacteroidetes bacterium clone CG84 accounted for 75% to 80% of the sequences on the biocathodes that showed higher electrochemical activity (60 and -100 mV). Copyright © 2012 Elsevier Ltd. All rights reserved.

GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

PubMed

Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

2014-01-05

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

Long-term Treatment with Oriental Medicinal Herb Artemisia princeps Alters Neuroplasticity in a Rat Model of Ovarian Hormone Deficiency.

PubMed

Kim, Hyun-Bum; Kwon, Byeong-Jae; Cho, Hyun-Ji; Kim, Ji-Won; Chon, Jeong-Woo; Do, Moon-Ho; Park, Sang-Yong; Kim, Sun-Yeou; Maeng, Sung-Ho; Park, Yoo-Kyoung; Park, Ji-Ho

2015-03-01

Artemisia princeps (AP) is a flowering perennial used as a traditional medicine and dietary supplement across East Asia. No study has yet assessed its effects on synaptic plasticity in hippocampus and much less in a model of ovarian hormone deficiency. We examined the influence of chronic oral AP ethanol extract treatment in ovariectomized rats on the induction of long-term depression in a representative synapse (CA3-CA1) of the hippocampus. Ovariectomized rats demonstrated lower trabecular mean bone mineral densities than sham, validating the establishment of pathology. Against this background of pathology, AP-treated ovariectomized rats exhibited attenuated long-term depression (LTD) in CA1 relative to water-treated controls as measured by increased field excitatory post-synaptic potentials (fEPSP) activation averages over the post-stimulation period. While pathological significance of long-term depression (LTD) in ovariectomized rats is conflicting, that AP treatment significantly affected its induction offers justification for further study of its influences on plasticity and its related disorders.

Long-term Treatment with Oriental Medicinal Herb Artemisia princeps Alters Neuroplasticity in a Rat Model of Ovarian Hormone Deficiency

PubMed Central

Kim, Hyun-Bum; Kwon, Byeong-Jae; Cho, Hyun-Ji; Kim, Ji-Won; Chon, Jeong-Woo; Do, Moon-Ho; Park, Sang-Yong; Kim, Sun-Yeou; Maeng, Sung-Ho; Park, Yoo-Kyoung

2015-01-01

Artemisia princeps (AP) is a flowering perennial used as a traditional medicine and dietary supplement across East Asia. No study has yet assessed its effects on synaptic plasticity in hippocampus and much less in a model of ovarian hormone deficiency. We examined the influence of chronic oral AP ethanol extract treatment in ovariectomized rats on the induction of long-term depression in a representative synapse (CA3-CA1) of the hippocampus. Ovariectomized rats demonstrated lower trabecular mean bone mineral densities than sham, validating the establishment of pathology. Against this background of pathology, AP-treated ovariectomized rats exhibited attenuated long-term depression (LTD) in CA1 relative to water-treated controls as measured by increased field excitatory post-synaptic potentials (fEPSP) activation averages over the post-stimulation period. While pathological significance of long-term depression (LTD) in ovariectomized rats is conflicting, that AP treatment significantly affected its induction offers justification for further study of its influences on plasticity and its related disorders. PMID:25792871

Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

PubMed

Takeda, Atsushi; Kanno, Shingo; Sakurada, Naomi; Ando, Masaki; Oku, Naoto

2008-10-01

The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. (c) 2008 Wiley-Liss, Inc.

Enhanced AMPA Receptor Function Promotes Cerebellar Long-Term Depression Rather than Potentiation

ERIC Educational Resources Information Center

van Beugen, Boeke J.; Qiao, Xin; Simmons, Dana H.; De Zeeuw, Chris I.; Hansel, Christian

2014-01-01

Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar…

Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus.

PubMed

Bellinger, F P; Madamba, S; Siggins, G R

1993-11-19

Cytokines such as interleukin-1 beta (IL-1 beta) are released in the nervous system following inflammation or infection. Recently, IL-1 beta was shown to enhance synaptic inhibitory mechanisms. We therefore investigated the effect of IL-1 beta superfusion on long-term potentiation (LTP), the cellular model of memory and learning, evoked in the CA1 region by tetanic stimulation of the stratum radiatum in the rat hippocampal slice. IL-1 beta (150 pM-1.5 nM) superfused 10 min before tetanic stimulation significantly reduced LTP of the slope of the population excitatory postsynaptic potential (pEPSP) and the population spike (PS) amplitude in CA1 in a concentration-dependent manner. IL-1 beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values before tetanus as well, although the PS returned to control values before tetanus. Heat-inactivated IL-1 beta had no effect on pre-tetanus pEPSP or PS values or the induction of LTP. These data demonstrate that IL-1 beta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1 beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dementia.

The role of GABA in NMDA-dependent long term depression (LTD) of rat medial vestibular nuclei.

PubMed

Grassi, S; Della Torre, G; Capocchi, G; Zampolini, M; Pettorossi, V E

1995-11-20

The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABAA and GABAB receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. This indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABAA receptors contribute to LTD more than GABAB do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

Ionotropic Glutamate Receptors and Voltage-Gated Ca2+ Channels in Long-Term Potentiation of Spinal Dorsal Horn Synapses and Pain Hypersensitivity

PubMed Central

Youn, Dong-ho; Gerber, Gábor; Sather, William A.

2013-01-01

Over the last twenty years of research on cellular mechanisms of pain hypersensitivity, long-term potentiation (LTP) of synaptic transmission in the spinal cord dorsal horn (DH) has emerged as an important contributor to pain pathology. Mechanisms that underlie LTP of spinal DH neurons include changes in the numbers, activity, and properties of ionotropic glutamate receptors (AMPA and NMDA receptors) and of voltage-gated Ca2+ channels. Here, we review the roles and mechanisms of these channels in the induction and expression of spinal DH LTP, and we present this within the framework of the anatomical organization and synaptic circuitry of the spinal DH. Moreover, we compare synaptic plasticity in the spinal DH with classical LTP described for hippocampal synapses. PMID:24224102

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex

NASA Technical Reports Server (NTRS)

Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

1996-01-01

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

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…

Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression.

PubMed

Nijhoff, M F; Engelse, M A; Dubbeld, J; Braat, A E; Ringers, J; Roelen, D L; van Erkel, A R; Spijker, H S; Bouwsma, H; van der Boog, P J M; de Fijter, J W; Rabelink, T J; de Koning, E J P

2016-01-01

Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory.

PubMed

Wang, Wei; Wang, Fang; Yang, Yuan-Jian; Hu, Zhuang-Li; Long, Li-Hong; Fu, Hui; Xie, Na; Chen, Jian-Guo

2011-03-01

There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal CA1 region and cognitive behavioural performance. Effects of baicalein on LTP in rat hippocampal slices were investigated by electrophysiological methods. Phosphorylation of Akt (at Ser(473)), the extracellular signal-regulated kinase (ERK1/2) and the transcription factor cAMP response element-binding protein (CREB) (at Ser(133)) were analysed by Western blot. Fear conditioning was used to determine whether baicalein could improve learning and memory in rats. Baicalein enhanced the N-methyl-d-aspartate glutamate receptor-dependent LTP in a bell-shaped concentration-dependent manner. Addition of the lipoxygenase metabolites 12(S)-HETE and 12(S)-HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell-shaped dose-response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3-kinase. CREB phosphorylation was also increased in the CA1 region of baicalein-treated slices. Baicalein-treated rats performed significantly better than controls in a hippocampus-dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training. Our results demonstrate that the flavonoid baicalein can facilitate memory, and therefore it might be useful in the treatment of patients with memory disorders. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

PubMed

Grassi, S; Frondaroli, A; Pessia, M; Pettorossi, V E

2001-08-08

In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

ERIC Educational Resources Information Center

Vedder, Lindsey C.; Savage, Lisa M.

2017-01-01

Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

Low-carbohydrate diets: what are the potential short- and long-term health implications?

PubMed

Bilsborough, Shane A; Crowe, Timothy C

2003-01-01

Low-carbohydrate diets for weight loss are receiving a lot of attention of late. Reasons for this interest include a plethora of low-carbohydrate diet books, the over-sensationalism of these diets in the media and by celebrities, and the promotion of these diets in fitness centres and health clubs. The re-emergence of low-carbohydrate diets into the spotlight has lead many people in the general public to question whether carbohydrates are inherently 'bad' and should be limited in the diet. Although low-carbohydrate diets were popular in the 1970s they have resurged again yet little scientific fact into the true nature of how these diets work or, more importantly, any potential for serious long-term health risks in adopting this dieting practice appear to have reached the mainstream literature. Evidence abounds that low-carbohydrate diets present no significant advantage over more traditional energy-restricted, nutritionally balanced diets both in terms of weight loss and weight maintenance. Studies examining the efficacy of using low-carbohydrate diets for long-term weight loss are few in number, however few positive benefits exist to promote the adoption of carbohydrate restriction as a realistic, and more importantly, safe means of dieting. While short-term carbohydrate restriction over a period of a week can result in a significant loss of weight (albeit mostly from water and glycogen stores), of serious concern is what potential exists for the following of this type of eating plan for longer periods of months to years. Complications such as heart arrhythmias, cardiac contractile function impairment, sudden death, osteoporosis, kidney damage, increased cancer risk, impairment of physical activity and lipid abnormalities can all be linked to long-term restriction of carbohydrates in the diet. The need to further explore and communicate the untoward side-effects of low-carbohydrate diets should be an important public health message from nutrition professionals.

Long-term variability of the thunderstorm and hail potential in Europe

NASA Astrophysics Data System (ADS)

Mohr, Susanna; Kunz, Michael; Speidel, Johannes; Piper, David

2016-04-01

Severe thunderstorms and associated hazardous weather events such as hail frequently cause considerable damage to buildings, crops, and automobiles, resulting in large monetary costs in many parts of Europe and the world. To relate single extreme hail events to the historic context and to estimate their return periods and possible trends related to climate change, long-term statistics of hail events are required. Due to the local-scale nature of hail and a lack of suitable observation systems, however, hailstorms are not captured reliably and comprehensively for a long period of time. In view of this fact, different proxies (indirect climate data) obtained from sounding stations and regional climate models can be used to infer the probability and intensity of thunderstorms or hailstorms. In contrast to direct observational data, such proxies are available homogeneously over a long time period. The aim of the study is to investigate the potential for severe thunderstorms and their changes over past decades. Statistical analyses of sounding data show that the convective potential over the past 20 - 30 years has significantly increased over large parts of Central Europe, making severe thunderstorms more likely. A similar picture results from analyses of weather types that are most likely associated with damaging hailstorms. These weather patterns have increased, even if only slightly but nevertheless statistically significantly, in the time period from 1971 to 2000. To improve the diagnostics of hail events in regional climate models, a logistic hail model has been developed by means of a multivariate analysis method. The model is based on a combination of appropriate hail-relevant meteorological parameters. The output of the model is a new index that estimates the potential of the atmosphere for hailstorm development, referred to as potential hail index (PHI). Applied to a high-resolved reanalysis run for Europe driven by NCEP/NCAR1, long-term changes of the PHI for

Dual Influence of Endocannabinoids on Long-Term Potentiation of Synaptic Transmission

PubMed Central

Silva-Cruz, Armando; Carlström, Mattias; Ribeiro, Joaquim A.; Sebastião, Ana M.

2017-01-01

Cannabinoid receptor 1 (CB1R) is widely distributed in the central nervous system, in excitatory and inhibitory neurons, and in astrocytes. CB1R agonists impair cognition and prevent long-term potentiation (LTP) of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs) on hippocampal LTP remains ambiguous. Based on the knowledge that eCBs are released upon high frequency neuronal firing, we hypothesized that the influence of eCBs upon LTP could change according to the paradigm of LTP induction. We thus tested the influence of eCBs on hippocampal LTP using two θ-burst protocols that induce either a weak or a strong LTP. LTP induced by a weak-θ-burst protocol is facilitated while preventing the endogenous activation of CB1Rs. In contrast, the same procedures lead to inhibition of LTP induced by the strong-θ-burst protocol, suggestive of a facilitatory action of eCBs upon strong LTP. Accordingly, an inhibitor of the metabolism of the predominant eCB in the hippocampus, 2-arachidonoyl-glycerol (2-AG), facilitates strong LTP. The facilitatory action of endogenous CB1R activation does not require the activity of inhibitory A1 adenosine receptors, is not affected by inhibition of astrocytic metabolism, but involves inhibitory GABAergic transmission. The continuous activation of CB1Rs via exogenous cannabinoids, or by drugs known to prevent metabolism of the non-prevalent hippocampal eCB, anandamide, inhibited LTP. We conclude that endogenous activation of CB1Rs by physiologically formed eCBs exerts a fine-tune homeostatic control of LTP in the hippocampus, acting as a high-pass filter, therefore likely reducing the signal-to-noise ratio of synaptic strengthening. PMID:29311928

Long-Term Visuo-Gustatory Appetitive and Aversive Conditioning Potentiate Human Visual Evoked Potentials

PubMed Central

Christoffersen, Gert R. J.; Laugesen, Jakob L.; Møller, Per; Bredie, Wender L. P.; Schachtman, Todd R.; Liljendahl, Christina; Viemose, Ida

2017-01-01

Human recognition of foods and beverages are often based on visual cues associated with flavors. The dynamics of neurophysiological plasticity related to acquisition of such long-term associations has only recently become the target of investigation. In the present work, the effects of appetitive and aversive visuo-gustatory conditioning were studied with high density EEG-recordings focusing on late components in the visual evoked potentials (VEPs), specifically the N2-P3 waves. Unfamiliar images were paired with either a pleasant or an unpleasant juice and VEPs evoked by the images were compared before and 1 day after the pairings. In electrodes located over posterior visual cortex areas, the following changes were observed after conditioning: the amplitude from the N2-peak to the P3-peak increased and the N2 peak delay was reduced. The percentage increase of N2-to-P3 amplitudes was asymmetrically distributed over the posterior hemispheres despite the fact that the images were bilaterally symmetrical across the two visual hemifields. The percentage increases of N2-to-P3 amplitudes in each experimental subject correlated with the subject’s evaluation of positive or negative hedonic valences of the two juices. The results from 118 scalp electrodes gave surface maps of theta power distributions showing increased power over posterior visual areas after the pairings. Source current distributions calculated from swLORETA revealed that visual evoked currents rose as a result of conditioning in five cortical regions—from primary visual areas and into the inferior temporal gyrus (ITG). These learning-induced changes were seen after both appetitive and aversive training while a sham trained control group showed no changes. It is concluded that long-term visuo-gustatory conditioning potentiated the N2-P3 complex, and it is suggested that the changes are regulated by the perceived hedonic valence of the US. PMID:28983243

Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage

PubMed Central

Prestori, Francesca; Bonardi, Claudia; Mapelli, Lisa; Lombardo, Paola; Goselink, Rianne; De Stefano, Maria Egle; Gandolfi, Daniela; Mapelli, Jonathan; Bertrand, Daniel; Schonewille, Martijn; De Zeeuw, Chris; D’Angelo, Egidio

2013-01-01

The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation. PMID:23741401

Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

NASA Astrophysics Data System (ADS)

Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K.; Aono, Masakazu

2011-08-01

Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs , , , ). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag2S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag2S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag2S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

Near-Term Actions to Address Long-Term Climate Risk

NASA Astrophysics Data System (ADS)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

PubMed

Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

2003-01-01

We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

Preferred hexoses influence long-term memory and induction of lactose catabolism by Streptococcus mutans.

PubMed

Zeng, Lin; Chen, Lulu; Burne, Robert A

2018-05-11

Bacteria prioritize sugar metabolism via carbohydrate catabolite repression, which regulates global gene expression to optimize the catabolism of preferred substrates. Here, we report an unusual long-term memory effect in certain Streptococcus mutans strains that alters adaptation to growth on lactose after prior exposure to glucose or fructose. In strain GS-5, cells that were first cultured on fructose then transferred to lactose displayed an exceptionally long lag (>11 h) and slower growth, compared to cells first cultured on glucose or cellobiose, which displayed a reduction in lag phase by as much as 10 h. Mutants lacking the cellobiose-PTS or phospho-β-glucosidase lost the accelerated growth on lactose associated with prior culturing on glucose. The memory effects of glucose or fructose on lactose catabolism were not as profound in strain UA159, but the lag phase was considerably shorter in mutants lacking the glucose-PTS EII Man Interestingly, when S. mutans was cultivated on lactose, significant quantities of free glucose accumulated in the medium, with higher levels found in the cultures of strains lacking EII Man , glucokinase, or both. Free glucose was also detected in cultures that were utilizing cellobiose or trehalose, albeit at lower levels. Such release of hexoses by S. mutans is likely of biological significance as it was found that cells required small amounts of glucose or other preferred carbohydrates to initiate efficient growth on lactose. These findings suggest that S. mutans modulates the induction of lactose utilization based on its prior exposure to glucose or fructose, which can be liberated from common disaccharides. IMPORTANCE. Understanding the molecular mechanisms employed by oral bacteria to control sugar metabolism is key to developing novel therapies for management of dental caries and other oral diseases. Lactose is a naturally occurring disaccharide that is abundant in dairy products and commonly ingested by humans. However, for

Long-term Functional and Survival Outcomes after Induction Chemotherapy and Risk-Based Definitive Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

PubMed Central

Hutcheson, Katherine A.; Lewin, Jan S.; Holsinger, F. Christopher; Steinhaus, Ganene; Lisec, Asher; Barringer, Denise A.; Lin, Heather Y.; Villalobos, Sandra; Garden, Adam S.; Papadimitrakopoulou, Vali; Kies, Merrill S.

2014-01-01

Purpose To evaluate long-term outcomes after induction chemotherapy followed by “risk-based” local therapy for squamous cell carcinoma of the head and neck (SCCHN). Methods Forty-seven patients (stage IV, ≥N2b) were enrolled in a Phase II trial. Baseline and 24-months functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. Results Five-year overall survival was 89% (95% CI: 81%-99%). A non-significant 13% average reduction in swallowing efficiency (OPSE) was observed at 24-months relative to baseline (p=0.191). MDADI scores approximated baseline at 24-months. Among 42 long-term survivors (median=5.9 years), 3 (7.1%) had chronic dysphagia. The rate of final gastrostomy-dependence was 4.8% (2/42). Conclusion Sequential chemoradiotherapy achieved favorable outcomes among patients with locally-advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. PMID:23780650

Reversal of Long-Term Potentiation-Like Plasticity Processes after Motor Learning Disrupts Skill Retention

PubMed Central

Cantarero, Gabriela; Lloyd, Ashley

2013-01-01

Plasticity of synaptic connections in the primary motor cortex (M1) is thought to play an essential role in learning and memory. Human and animal studies have shown that motor learning results in long-term potentiation (LTP)-like plasticity processes, namely potentiation of M1 and a temporary occlusion of additional LTP-like plasticity. Moreover, biochemical processes essential for LTP are also crucial for certain types of motor learning and memory. Thus, it has been speculated that the occlusion of LTP-like plasticity after learning, indicative of how much LTP was used to learn, is essential for retention. Here we provide supporting evidence of it in humans. Induction of LTP-like plasticity can be abolished using a depotentiation protocol (DePo) consisting of brief continuous theta burst stimulation. We used transcranial magnetic stimulation to assess whether application of DePo over M1 after motor learning affected (1) occlusion of LTP-like plasticity and (2) retention of motor skill learning. We found that the magnitude of motor memory retention is proportional to the magnitude of occlusion of LTP-like plasticity. Moreover, DePo stimulation over M1, but not over a control site, reversed the occlusion of LTP-like plasticity induced by motor learning and disrupted skill retention relative to control subjects. Altogether, these results provide evidence of a link between occlusion of LTP-like plasticity and retention and that this measure could be used as a biomarker to predict retention. Importantly, attempts to reverse the occlusion of LTP-like plasticity after motor learning comes with the cost of reducing retention of motor learning. PMID:23904621

Opposing Actions of Chronic[Deta][superscript 9] Tetrahydrocannabinol and Cannabinoid Antagonists on Hippocampal Long-Term Potentiation

ERIC Educational Resources Information Center

Hoffman, Alexander F.; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Lupica, Carl R.

2007-01-01

Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]-tetrahydrocannabinol ([Deta][superscript 9]-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for…

Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory in Aplysia

PubMed Central

Krishnan, Harini C.; Gandour, Catherine E.; Ramos, Joshua L.; Wrinkle, Mariah C.; Sanchez-Pacheco, Joseph J.; Lyons, Lisa C.

2016-01-01

Study Objectives: Insufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk Aplysia californica, a relatively simple model system well known for studies of learning and memory. Methods: Aplysia were sleep deprived for 9 hours using context changes and tactile stimulation either prior to or after training for the operant learning paradigm, learning that food is inedible (LFI). The effects of sleep deprivation on short-term (STM) and long-term memory (LTM) were assessed. Results: Acute sleep deprivation prior to LFI training impaired the induction of STM and LTM with persistent effects lasting at least 24 h. Sleep deprivation immediately after training blocked the consolidation of LTM. However, sleep deprivation following the period of molecular consolidation did not affect memory recall. Memory impairments were independent of handling-induced stress, as daytime handled control animals demonstrated no memory deficits. Additional training immediately after sleep deprivation failed to rescue the induction of memory, but additional training alleviated the persistent impairment in memory induction when training occurred 24 h following sleep deprivation. Conclusions: Acute sleep deprivation inhibited the induction and consolidation, but not the recall of memory. These behavioral studies establish Aplysia as an effective model system for studying the interactions between sleep and memory formation. Citation: Krishnan HC, Gandour CE, Ramos JL, Wrinkle MC, Sanchez-Pacheco JJ, Lyons LC. Acute sleep deprivation blocks short- and long-term operant memory in Aplysia. SLEEP 2016;39(12):2161–2171. PMID:27748243

Intelligent power wheelchair use in long-term care: potential users' experiences and perceptions.

PubMed

Rushton, Paula W; Mortenson, Ben W; Viswanathan, Pooja; Wang, Rosalie H; Miller, William C; Hurd Clarke, Laura

2017-10-01

Long-term care (LTC) residents with cognitive impairments frequently experience limited mobility and participation in preferred activities. Although a power wheelchair could mitigate some of these mobility and participation challenges, this technology is often not prescribed for this population due to safety concerns. An intelligent power wheelchair (IPW) system represents a potential intervention that could help to overcome these concerns. The purpose of this study was to explore a) how residents experienced an IPW that used three different modes of control and b) what perceived effect the IPW would have on their daily lives. We interviewed 10 LTC residents with mild or moderate cognitive impairment twice, once before and once after testing the IPW. Interviews were conducted using a semi-structured interview guide, audio recorded and transcribed verbatim for thematic analyses. Our analyses identified three overarching themes: (1) the difference an IPW would make, (2) the potential impact of the IPW on others and (3) IPW-related concerns. Findings from this study confirm the need for and potential benefits of IPW use in LTC. Future studies will involve testing IPW improvements based on feedback and insights from this study. Implications for rehabilitation Intelligent power wheelchairs may enhance participation and improve safety and feelings of well-being for long-term care residents with cognitive impairments. Intelligent power wheelchairs could potentially have an equally positive impact on facility staff, other residents, and family and friends by decreasing workload and increasing safety.

Circadian Regulation of Hippocampal Long-Term Potentiation

PubMed Central

Chaudhury, Dipesh; Wang, Louisa M.; Colwell, Christopher S.

2008-01-01

The goal of this study is to investigate the possible circadian regulation of hippocampal excitability and long-term potentiation (LTP) measured by stimulating the Schaffer collaterals (SC) and recording the field excitatory postsynaptic potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of interest because the C3H mice secrete melatonin rhythmically while the C57 mice do not. The authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from night slices compared to day slices of both C3H and C57 mice. They also found significant diurnal variation in the decay of LTP measured with fEPSPs, with the decay slower during the night in both strains of mice. There was evidence for a diurnal rhythm in the input/output function of pyramidal neurons measured at the soma in C57 but not C3H mice. Furthermore, LTP in the PS, measured in slices prepared during the day but recorded during the night, had a profile remarkably similar to the night group. Finally, PS recordings were carried out in slices from C3H mice maintained in constant darkness prior to experimentation. Again, the authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from subjective night slices compared to subjective day slices. These results provide the 1st evidence that an endogenous circadian oscillator modulates synaptic plasticity in the hippocampus. PMID:15851529

Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

2007-08-17

For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activitiesmore » remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs.« less

Synaptic Long-Term Potentiation and Depression in the Rat Medial Vestibular Nuclei Depend on Neural Activation of Estrogenic and Androgenic Signals

PubMed Central

Scarduzio, Mariangela; Panichi, Roberto; Pettorossi, Vito Enrico; Grassi, Silvarosa

2013-01-01

Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids. PMID:24265837

Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

PubMed

Scarduzio, Mariangela; Panichi, Roberto; Pettorossi, Vito Enrico; Grassi, Silvarosa

2013-01-01

Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

Inductive Learning: Does Interleaving Exemplars Affect Long-Term Retention?

ERIC Educational Resources Information Center

Zulkiply, Norehan; Burt, Jennifer S.

2013-01-01

Purpose: The present study investigated whether or not the benefits of interleaving of exemplars from several categories vary with retention interval in inductive learning. Methodology: Two experiments were conducted using paintings (Experiment 1) and textual materials (Experiment 2), and the experiments used a mixed factorial design. Forty…

An Induction Heating Method with Traveling Magnetic Field for Long Structure Metal

NASA Astrophysics Data System (ADS)

Sekine, Takamitsu; Tomita, Hideo; Obata, Shuji; Saito, Yukio

A novel dismantlable adhesion method for recycling operation of interior materials is proposed. This method is applied a high frequency induction heating and a thermoplastic adhesive. For an adhesion of interior material to long steel stud, a conventional spiral coil as like IH cooking heater gives inadequateness for uniform heating to the stud. Therefore, we have proposed an induction heating method with traveling magnetic field for perfect long structures bonding. In this paper, we describe on the new adhesion method using the 20kHz, three-phase 200V inverter and linear induction coil. From induction heating characteristics to thin steel plates and long studs, the method is cleared the usefulness for uniform heating to long structures.

Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses.

PubMed

Kakegawa, Wataru; Tsuzuki, Keisuke; Yoshida, Yukari; Kameyama, Kimihiko; Ozawa, Seiji

2004-07-01

Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca(2+)-impermeable AMPARs at these synapses were replaced with exogenous Ca(2+)-permeable receptors, and Ca(2+) influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca(2+)/calmodulin-dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.

Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome.

PubMed

Morice, Elise; Andreae, Laura C; Cooke, Sam F; Vanes, Lesley; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Bliss, Timothy V P

2008-07-01

Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of the human chromosome 21 (Hsa21). Recently, O'Doherty and colleagues in an earlier study generated a new genetic mouse model of DS (Tc1) that carries an almost complete Hsa21. Since DS is the most common genetic cause of mental retardation, we have undertaken a detailed analysis of cognitive function and synaptic plasticity in Tc1 mice. Here we show that Tc1 mice have impaired spatial working memory (WM) but spared long-term spatial reference memory (RM) in the Morris watermaze. Similarly, Tc1 mice are selectively impaired in short-term memory (STM) but have intact long-term memory (LTM) in the novel object recognition task. The pattern of impaired STM and normal LTM is paralleled by a corresponding phenotype in long-term potentiation (LTP). Freely-moving Tc1 mice exhibit reduced LTP 1 h after induction but normal maintenance over days in the dentate gyrus of the hippocampal formation. Biochemical analysis revealed a reduction in membrane surface expression of the AMPAR (alpha-amino-3-hydroxy-5-methyl-4-propionic acid receptor) subunit GluR1 in the hippocampus of Tc1 mice, suggesting a potential mechanism for the impairment in early LTP. Our observations also provide further evidence that STM and LTM for hippocampus-dependent tasks are subserved by parallel processing streams.

Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

PubMed Central

Ballesteros, Kristen A; Sikorski, Angela; Orfila, James E; Martinez, Joe L

2012-01-01

Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA) receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP) in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3). We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3) to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA), or 3-[(R)-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP). Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals anesthetized with isoflurane compared to those anesthetized with sodium pentobarbital. The results suggest that isoflurane may affect amplitude through activation of GABAA receptors or mechanisms important to LTP in CA3 afferent fibers. PMID:23204857

Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

PubMed

Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

2017-04-01

Hydrogen sulfide (H 2 S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H 2 S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H 2 S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H 2 S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H 2 S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H 2 S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H 2 S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H 2 S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H 2 S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

PubMed

Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

2015-12-01

Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

Long-term functional and survival outcomes after induction chemotherapy and risk-based definitive therapy for locally advanced squamous cell carcinoma of the head and neck.

PubMed

Hutcheson, Katherine A; Lewin, Jan S; Holsinger, F Christopher; Steinhaus, Ganene; Lisec, Asher; Barringer, Denise A; Lin, Heather Y; Villalobos, Sandra; Garden, Adam S; Papadimitrakopoulou, Vali; Kies, Merrill S

2014-04-01

The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by "risk-based" local therapy for locally-advanced squamous cell carcinoma of the head and neck (SCCHN). Forty-seven patients (stage IV; ≥N2b) were enrolled in a phase II trial. Baseline and 24-month functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. Five-year overall survival (OS) was 89% (95% confidence interval [CI], 81% to 99%). A nonsignificant 13% average reduction in swallowing efficiency (OPSE) was observed at 24 months relative to baseline (p = .191). MDADI scores approximated baseline at 24 months. Among 42 long-term survivors (median, 5.9 years), 3 patients (7.1%) had chronic dysphagia. The rate of final gastrostomy dependence was 4.8% (2 of 42). Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. Copyright © 2013 Wiley Periodicals, Inc.

Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

NASA Astrophysics Data System (ADS)

Ordikhani, F.; Simchi, A.

2014-10-01

Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

Mechanisms of hippocampal long-term depression are required for memory enhancement by novelty exploration.

PubMed

Dong, Zhifang; Gong, Bo; Li, Hongjie; Bai, Yanrui; Wu, Xiaoyan; Huang, Yan; He, Wenting; Li, Tingyu; Wang, Yu Tian

2012-08-29

It is well known that novel environments can enhance learning and memory. However, the underlying mechanisms remain poorly understood. Here, we report that, in freely moving rats, novelty exploration facilitates the production of hippocampal CA1 long-term depression (LTD), a well characterized form of synaptic plasticity believed to be a cellular substrate of spatial learning, and thereby converts short-term memory (STM) into long-term memory (LTM) in an inhibitory avoidance learning procedure. Blocking the induction or the expression of CA1 LTD with two mechanistically and structurally distinct inhibitors prevents not only novelty acquisition but also the novelty exploration-promoted conversion of STM into LTM. Moreover, production of LTD with a strong electrical stimulation induction protocol or facilitation of hippocampal LTD by pharmacological inhibition of glutamate transporter activity mimics the behavioral effects of novelty exploration, sufficiently promoting the conversion of STM into LTM. Together, our findings suggest that induction of LTD may play an essential role not only in novelty acquisition but also in novelty-mediated memory enhancement.

Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

PubMed Central

Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

2015-01-01

Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects. PMID:26483631

Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat.

PubMed

Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

2015-01-01

Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

An overview of potential labor-saving and quality-improving innovations in long-term care for older people.

PubMed

Thoma-Lürken, Theresa; Bleijlevens, Michel H C; Lexis, Monique A S; Hamers, Jan P H; de Witte, Luc P

2015-06-01

Increasing demands in long-term care for older people and a decrease in workforce availability can be expected in the future. These developments challenge the sustainability and quality of long-term care for older people. To address these challenges, long-term care organizations are forced to innovate. The aim of this study is to provide an overview of potential labor-saving and quality-improving innovations long-term care organizations are working on and to assess the self-reported extent of effectiveness. This is a descriptive cross-sectional study. In total, 32 long-term care organizations in the region of Limburg in The Netherlands were invited to participate in the study. The inventory was performed by means of semistructured interviews with chief executive officers, managers, and staff members of the long-term care organizations. Based on the interview data, all innovations were described in a standardized form and subsequently checked by the participants. All innovations were clustered into product, process, organizational, and marketing innovations. In total, 26 long-term care organizations delivering home and/or institutional long-term care for older people participated in the study. Overall, 228 innovations were identified; some innovations were described in a similar way by different organizations. The majority of innovations were product innovations (n = 96), followed by organizational innovations (n = 75), and process innovations (n = 42). In addition to the main types, 15 other innovations incorporating characteristics of different types of innovations were detected. Little evidence about the effectiveness of the innovations was reported by the organizations. This study shows that a large number and a broad variety of innovations have been implemented or are currently being developed in long-term care organizations for older people. However, according to the organizations, there is relatively little (scientific) evidence confirming the effectiveness

Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit.

PubMed

Lamsa, Karri P; Heeroma, Joost H; Somogyi, Peter; Rusakov, Dmitri A; Kullmann, Dimitri M

2007-03-02

Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity.

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

PubMed Central

Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

Fertility treatment: long-term growth and mental development of the children.

PubMed

Bay, Bjørn

2014-10-01

Fertility treatment has been associated with obstetrical and perinatal complications. It is, however, uncertain whether fertility treatment or parental subfertility is associated with long-term development of the children. We aimed to assess the growth and mental health of children and adolescents conceived after fertility treatment compared to spontaneously conceived controls. First, we evaluated all previous studies comparing neurodevelopmental outcomes between children conceived after fertility treatment and spontaneous conceived controls. The systematic review clarified methodological limitations in the existing literature on the long-term development of children conceived after medical assisted reproduction. Although several studies had been published, large, well-controlled studies with long-term follow-up and thorough statistical adjustments were still few. Second, we evaluated the children's mental health by assessing the risk of mental disorders. We studied a population of 555,828 children conceived after spontaneous conception and 33,139 children conceived after fertility treatment with follow-up in 2012 when the children were 8-17 years old. The absolute risk and hazard ratio of overall and specific mental disorders were estimated while adjusting for potential confounding variables. Further, we estimated the association between subtypes of procedures, hormonal treatment, gamete types and cause of infertility on the one hand and the risk of mental disorders on the other. Children conceived after ovulation induction had a low, but significantly increased risks of autism spectrum disorders, hyperkinetic disorders, conduct, emotional, or social disorders, and tic disorders. Children conceived after IVF or ICSI showed no increased risk, except for a small risk of tic disorders. There was no risk systematically related to any specific type of hormone drug treatment. Thus, the increased risks may rely on residual confounding such as unknown parental factors

Acute Sleep Deprivation Blocks Short- and Long-Term Operant Memory in Aplysia.

PubMed

Krishnan, Harini C; Gandour, Catherine E; Ramos, Joshua L; Wrinkle, Mariah C; Sanchez-Pacheco, Joseph J; Lyons, Lisa C

2016-12-01

Insufficient sleep in individuals appears increasingly common due to the demands of modern work schedules and technology use. Consequently, there is a growing need to understand the interactions between sleep deprivation and memory. The current study determined the effects of acute sleep deprivation on short and long-term associative memory using the marine mollusk Aplysia californica , a relatively simple model system well known for studies of learning and memory. Aplysia were sleep deprived for 9 hours using context changes and tactile stimulation either prior to or after training for the operant learning paradigm, learning that food is inedible (LFI). The effects of sleep deprivation on short-term (STM) and long-term memory (LTM) were assessed. Acute sleep deprivation prior to LFI training impaired the induction of STM and LTM with persistent effects lasting at least 24 h. Sleep deprivation immediately after training blocked the consolidation of LTM. However, sleep deprivation following the period of molecular consolidation did not affect memory recall. Memory impairments were independent of handling-induced stress, as daytime handled control animals demonstrated no memory deficits. Additional training immediately after sleep deprivation failed to rescue the induction of memory, but additional training alleviated the persistent impairment in memory induction when training occurred 24 h following sleep deprivation. Acute sleep deprivation inhibited the induction and consolidation, but not the recall of memory. These behavioral studies establish Aplysia as an effective model system for studying the interactions between sleep and memory formation. © 2016 Associated Professional Sleep Societies, LLC.

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.

Consider long-term care as service alternative.

PubMed

Loria, L S

1987-04-01

The increasing demand for elderly care services, pressures on inpatient average length of stay and payment levels, and potential financial rewards from providing additional services, makes long-term care look attractive to hospitals. Long-term care, however, is not for every hospital. Before deciding to establish long-term care services, management should examine how the service fits within the hospital's strategic plan. The action plan below provides guidance in evaluating a decision to use hospital facilities for long-term care. Examine how long-term care services fit within the hospital's strategic plan. Study area demographics and competitors to assess the need and supply of long-term care services. Survey the medical staff, consumers and payers to determine attitudes, perceptions and interests regarding long-term care services. Develop a facility plan that identifies areas of excess capacity that can be most easily converted into long-term care with minimal effects on hospital operations. Prepare a financial feasibility analysis of the contribution margin and return on investment attributable to long-term care services. Include an impact analysis on hospital operations. Establish a management task force to develop a detailed implementation plan including assigned individual responsibilities and related timetable. Develop an effective marketing plan designed to generate increased patient market share.

Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses via cannabinoid signaling.

PubMed

Rinaldo, Lorenzo; Hansel, Christian

2013-07-02

Muscarinic acetylcholine receptors (mAChRs) are known to modulate synaptic plasticity in various brain areas. A signaling pathway triggered by mAChR activation is the production and release of endocannabinoids that bind to type 1 cannabinoid receptors (CB1R) located on synaptic terminals. Using whole-cell patch-clamp recordings from rat cerebellar slices, we have demonstrated that the muscarinic agonist oxotremorine-m (oxo-m) blocks the induction of presynaptic long-term potentiation (LTP) at parallel fiber (PF)-Purkinje cell synapses in a CB1R-dependent manner. Under control conditions, LTP was induced by delivering 120 PF stimuli at 8 Hz. In contrast, no LTP was observed when oxo-m was present during tetanization. PF-LTP was restored when the CB1R antagonist N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251) was coapplied with oxo-m. Furthermore, the suppressive effect of oxo-m on PF-LTP was abrogated by the GDP analog GDP-β-S (applied intracellularly), the phospholipase C inhibitor U-73122, and the diacylglycerol lipase inhibitor tetrahydrolipstatin (THL), suggesting that cannabinoid synthesis results from the activation of Gq-coupled mAChRs present on Purkinje cells. The oxo-m-mediated suppression of LTP was also prevented in the presence of the M3 receptor antagonist DAU 5884, and was absent in M1/M3 receptor double-KO mice, identifying M3 receptors as primary oxo-m targets. Our findings allow for the possibility that cholinergic signaling in the cerebellum--which may result from long-term depression (LTD)-related disinhibition of cholinergic neurons in the vestibular nuclei--suppresses presynaptic LTP to prevent an up-regulation of transmitter release that opposes the reduction of postsynaptic responsiveness. This modulatory capacity of mAChR signaling could promote the functional penetrance of LTD.

Long-term potential and actual evapotranspiration of two different forests on the Atlantic Coastal Plain

Treesearch

Devendra Amatya; S. Tian; Z. Dai; Ge Sun

2016-01-01

A reliable estimate of potential evapotranspiration (PET) for a forest ecosystem is critical in ecohydrologic modeling related with water supply, vegetation dynamics, and climate change and yet is a challenging task due to its complexity. Based on long-term on-site measured hydro-climatic data and predictions from earlier validated hydrologic modeling studies...

Decreased term and postterm birthweight in the United States: impact of labor induction.

PubMed

Zhang, Xun; Joseph, K S; Kramer, Michael S

2010-08-01

We sought to assess recent trends in falling mean birthweight (BW) and gestational age (GA) among US non-Hispanic white singleton live births >or=37 weeks of gestation and the contribution of increased rates of induction to these trends. This was an ecological study based on US vital statistics from 1992 through 2003. From 1992 through 2003, mean BW fell by 37 g, mean GA by 3 days, and macrosomia rates by 25%. Rates of induction nearly doubled from 14% to 27%. Our ecological state-level analysis showed that the increased rate of induction was significantly associated with reduced mean BW (r = -0.54; 95% confidence interval [CI], -0.71 to -0.29), mean GA (r = -0.44; 95% CI, -0.65 to -0.17), and rate of macrosomia (r = -0.55; 95% CI, -0.74 to -0.32). Increasing use of induction is a likely cause of the observed recent declines in BW and GA. The impact of these trends on infant and long-term health warrants attention and investigation. Copyright (c) 2010 Mosby, Inc. All rights reserved.

The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

PubMed Central

Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

2011-01-01

Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

PubMed

Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

2008-08-21

Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation.

PubMed

Nahuis, M J; Oude Lohuis, E; Kose, N; Bayram, N; Hompes, P; Oosterhuis, G J E; Kaaijk, E M; Cohlen, B J; Bossuyt, P P M; van der Veen, F; Mol, B W; van Wely, M

2012-12-01

Laparoscopic electrocautery of the ovaries and ovulation induction with gonadotrophins are both second line treatments for women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Long-term follow-up after electrocautery versus ovulation induction with gonadotrophins has demonstrated at least comparable chances for a first live born child with a reduced need for ovulation induction or assisted reproduction treatment and increased chances for a second live born child. In this study, we report on the long-term economic consequences of both treatment modalities. Between February 1998 and October 2001, we performed a multi-centre randomized controlled trial (RCT) comparing a strategy of laparoscopic electrocautery of the ovaries, followed by clomiphene citrate and gonadotrophins when anovulation persisted, and a strategy of ovulation induction with gonadotrophins in women with clomiphene citrate-resistant PCOS. Eight to twelve years after randomization we performed a follow-up study on reproductive outcome in these women and the fertility treatments they had needed including data on direct medical costs of pregnancy and delivery. Clinical data included number of treatment cycles, live births, miscarriages, ectopic pregnancies and multiple pregnancies. We calculated mean costs per woman after randomization until the first live birth. Confidence intervals (CIs) were estimated by bootstrapping. We obtained data for an economic analysis on 159 of the 168 randomized women (95%). In total, 71 of 83 women (86%) allocated to the electrocautery strategy and 69 of 85 women (81%) allocated to the gonadotrophin strategy had at least one live birth. Given the equivalence between the two treatment strategies in terms of a first live birth-the primary outcome measure-our analysis focused on the cost difference between the two strategies within a mean follow-up time of 8-12 years. The mean costs per first live birth after randomization were €11 176 (95% CI: €9689

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

Long-Term Opioid Therapy Reconsidered

PubMed Central

Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A.; Chou, Roger

2012-01-01

In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment. PMID:21893626

Effective potentials for H2O-He and H2O-Ar systems. Isotropic induction-dispersion potentials

NASA Astrophysics Data System (ADS)

Starikov, Vitali I.; Petrova, Tatiana M.; Solodov, Alexander M.; Solodov, Alexander A.; Deichuli, Vladimir M.

2017-05-01

The vibrational and rotational dependence of the effective isotropic interaction potential of H2O-He and H2O-Ar systems, taken in the form of Lennard-Jones 6-12 potential has been analyzed. The analysis is based on the experimental line broadening (γ) and line shift (δ) coefficients obtained for different vibrational bands of H2O molecule perturbed by He and Ar. The first and second derivatives of the function C(1)(q) for the long-range part of the induction-dispersion potential with respect to the dimensionless normal coordinates q were calculated using literature information for the dipole moment and mean polarizability functions μ(q) and α(q), respectively. These derivatives have been used in the calculations of the quantities which determine the vibrational and rotational dependence of the long-range part of the effective isotropic potential. The optimal set of the derivatives for the function C(1)(q) is proposed. The comparison with the experimental data has been performed.

Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release.

PubMed

Younts, Thomas J; Monday, Hannah R; Dudok, Barna; Klein, Matthew E; Jordan, Bryen A; Katona, István; Castillo, Pablo E

2016-10-19

Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB 1 )-expressing axons. This long-term depression of inhibitory transmission (iLTD) involves cap-dependent protein synthesis in presynaptic interneuron axons, but not somata. Translation is required during the induction, but not maintenance, of iLTD. Mechanistically, CB 1 activation enhances protein synthesis via the mTOR pathway. Furthermore, using super-resolution STORM microscopy, we revealed eukaryotic ribosomes in CB 1 -expressing axon terminals. These findings suggest that presynaptic local protein synthesis controls neurotransmitter release during long-term plasticity in the mature mammalian brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural and molecular remodeling of dendritic spine substructures during long-term potentiation

PubMed Central

Bosch, Miquel; Castro, Jorge; Saneyoshi, Takeo; Matsuno, Hitomi; Sur, Mriganka; Hayashi, Yasunori

2014-01-01

SUMMARY Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four distinct patterns through three sequential phases. In the initial phase, the actin cytoskeleton was rapidly remodeled while active cofilin was massively transported to the spine. In the stabilization phase, cofilin formed a stable complex with F-actin, was persistently retained at the spine, and consolidated spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until a late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time. PMID:24742465

What Legislators Need to Know about Long-Term Care Insurance.

ERIC Educational Resources Information Center

Landes, David

This booklet discusses the potential importance to states of long-term care insurance, describes general policy characteristics, and summarizes state actions to both regulate and promote long-term care insurance. It is intended as a resource for legislators and others involved in long-term care financing and public policy formulation. Long-term…

Long-Term Memory Performance in Adult ADHD.

PubMed

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Long-term climate change mitigation potential with organic matter management on grasslands.

PubMed

Ryals, Rebecca; Hartman, Melannie D; Parton, William J; DeLonge, Marcia S; Silver, Whendee L

2015-03-01

Compost amendments to grasslands have been proposed as a strategy to mitigate climate change through carbon (C) sequestration, yet little research exists exploring the net mitigation potential or the long-term impacts of this strategy. We used field data and the DAYCENT biogeochemical model to investigate the climate change mitigation potential of compost amendments to grasslands in California, USA. The model was used to test ecosystem C and greenhouse gas responses to a range of compost qualities (carbon to nitrogen [C:N] ratios of 11.1, 20, or 30) and application rates (single addition of 14 Mg C/ha or 10 annual additions of 1.4 Mg C · ha(-1) · yr(-1)). The model was parameterized using site-specific weather, vegetation, and edaphic characteristics and was validated by comparing simulated soil C, nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2) fluxes, and net primary production (NPP) with three years of field data. All compost amendment scenarios led to net greenhouse gas sinks that persisted for several decades. Rates of climate change mitigation potential ranged from 130 ± 3 g to 158 ± 8 g CO2-eq · m(-2) ·yr(-1) (where "eq" stands for "equivalents") when assessed over a 10-year time period and 63 ± 2 g to 84 ± 10 g CO2- eq · m(-2) · yr(-1) over a 30-year time period. Both C storage and greenhouse gas emissions increased rapidly following amendments. Compost amendments with lower C:N led to higher C sequestration rates over time. However, these soils also experienced greater N20 fluxes. Multiple smaller compost additions resulted in similar cumulative C sequestration rates, albeit with a time lag, and lower cumulative N2O emissions. These results identify a trade-off between maximizing C sequestration and minimizing N2O emissions following amendments, and suggest that compost additions to grassland soils can have a long-term impact on C and greenhouse gas dynamics that contributes to climate change mitigation.

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory.

PubMed

Tsai, Sheng-Feng; Ku, Nai-Wen; Wang, Tzu-Feng; Yang, Yan-Hsiang; Shih, Yao-Hsiang; Wu, Shih-Ying; Lee, Chu-Wan; Yu, Megan; Yang, Ting-Ting; Kuo, Yu-Min

2018-05-07

Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline. © 2018 S. Karger AG, Basel.

Effect of agmatine on long-term potentiation in morphine-treated rats.

PubMed

Lu, Wei; Dong, Hua-Jin; Bi, Guo-Hua; Zhao, Yong-Qi; Yang, Zheng; Su, Rui-Bin; Li, Jin

2010-08-01

Agmatine is an endogenous amine derived from l-arginine that potentiates morphine analgesia and inhibits naloxone precipitated abstinent symptoms in morphine dependent rats. In this study, the effects of agmatine on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG) on saline or morphine-treated rats were investigated. Population spikes (PS), evoked by stimulation of the LPP, was recorded from DG region. Acute agmatine (2.5-10mg/kg, s.c.) treatment facilitated hippocampal LTP. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and agmatine (10mg/kg, s.c.) restored the amplitude of PS that was attenuated by morphine. Chronic morphine treatment resulted in the enhancement of hippocampal LTP, agmatine co-administered with morphine significantly attenuated the enhancement of morphine on hippocampal LTP. Imidazoline receptor antagonist idazoxan (5mg/kg, i.p.) reversed the effect of agmatine. These results suggest that agmatine attenuated the effect of morphine on hippocampal LTP, possibly through activation of imidazoline receptor. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

Impairments of long-term depression induction and motor coordination precede Aβ accumulation in the cerebellum of APPswe/PS1dE9 double transgenic mice.

PubMed

Kuwabara, Yuki; Ishizeki, Masato; Watamura, Naoto; Toba, Junya; Yoshii, Aya; Inoue, Takafumi; Ohshima, Toshio

2014-08-01

Alzheimer's disease (AD) is a neurodegenerative disorder that represents the most common type of dementia among elderly people. Amyloid beta (Aβ) peptides in extracellular Aβ plaques, produced from the amyloid precursor protein (APP) via sequential processing by β- and γ-secretases, impair hippocampal synaptic plasticity, and cause cognitive dysfunction in AD patients. Here, we report that Aβ peptides also impair another form of synaptic plasticity; cerebellar long-term depression (LTD). In the cerebellum of commonly used AD mouse model, APPswe/PS1dE9 mice, Aβ plaques were detected from 8 months and profound accumulation of Aβ plaques was observed at 18 onths of age. Biochemical analysis revealed relatively high levels of APP protein and Aβ in the cerebellum of APPswe/PS1dE9 mice. At pre-Aβ accumulation stage, LTD induction, and motor coordination are disturbed. These results indicate that soluble Aβ oligomers disturb LTD induction and cerebellar function in AD mouse model. © 2014 International Society for Neurochemistry.

Corticosterone Time-Dependently Modulates [beta]-Adrenergic Effects on Long-Term Potentiation in the Hippocampal Dentate Gyrus

ERIC Educational Resources Information Center

Pu, Zhenwei; Krugers, Harm J.; Joels, Marian

2007-01-01

Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining whether corticosterone exerts opposite effects on…

Transcriptional Correlates of Memory Maintenance Following Long-Term Sensitization of "Aplysia Californica"

ERIC Educational Resources Information Center

Conte, Catherine; Herdegen, Samantha; Kamal, Saman; Patel, Jency; Patel, Ushma; Perez, Leticia; Rivota, Marissa; Calin-Jageman, Robert J.; Calin-Jageman, Irina E.

2017-01-01

We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of "Aplysia californica" using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a…

miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

NASA Astrophysics Data System (ADS)

Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

2014-02-01

Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

Long-term changes in pigmentation of arctic Daphnia provide potential for reconstructing aquatic UV exposure

NASA Astrophysics Data System (ADS)

Nevalainen, Liisa; Rantala, Marttiina V.; Luoto, Tomi P.; Ojala, Antti E. K.; Rautio, Milla

2016-07-01

Despite the biologically damaging impacts of solar ultraviolet radiation (UV) in nature, little is known about its natural variability, forcing mechanisms, and long-term effects on ecosystems and organisms. Arctic zooplankton, for example the aquatic keystone genus Daphnia (Crustacea, Cladocera) responds to biologically damaging UV by utilizing photoprotective strategies, including pigmentation. We examined the preservation and content of UV-screening pigments in fossil Daphnia remains (ephippia) in two arctic lake sediment cores from Cornwallis Island (Lake R1), Canada, and Spitsbergen (Lake Fugledammen), Svalbard. The aims were to document changes in the degree of UV-protective pigmentation throughout the past centuries, elucidate the adaptive responses of zooplankton to long-term variations in UV exposure, and estimate the potential of fossil zooplankton pigments in reconstructing aquatic UV regimes. The spectroscopic absorbance measurements of fossil Daphnia ephippia under UV (280-400 nm) and visible light (400-700 nm) spectral ranges indicated that melanin (absorbance maxima at UV wavebands 280-350 nm) and carotenoids (absorbance maxima at 400-450 nm) pigments were preserved in the ephippia in both sediment cores. Downcore measurements of the most important UV-protective pigment melanin (absorbance measured at 305 and 340 nm) showed marked long-term variations in the degree of melanisation. These variations likely represented long-term trends in aquatic UV exposure and were positively related with solar radiation intensity. The corresponding trends in melanisation and solar activity were disrupted at the turn of the 20th century in R1, but remained as strong in Fugledammen. The reversed trends in the R1 core were simultaneous with a significant aquatic community reorganization taking place in the lake, suggesting that recent environmental changes, likely related to climate warming had a local effect on pigmentation strategies. This time horizon is also

Ex vivo expanded cord blood cells provide rapid engraftment in fetal sheep but lack long-term engrafting potential.

PubMed

McNiece, Ian K; Almeida-Porada, Graça; Shpall, Elizabeth J; Zanjani, Esmail

2002-06-01

Cord blood (CB) products are becoming routinely used in unrelated allogeneic transplantation for smaller pediatric patients. Because of the low numbers of cells in CB compared to bone marrow or peripheral blood progenitor cells, their use is more limited in larger adults. Therefore, we developed ex vivo expansion conditions for CB and currently are transplanting ex vivo expanded CB products to patients receiving high-dose chemotherapy. As there is concern that ex vivo expansion may exhaust long-term engrafting cells, the current clinical protocols consist of both an expanded fraction and an unexpanded fraction. To determine the effect of expansion culture on long-term engrafting cells, we evaluated the short- and long-term engrafting potential of ex vivo expanded CB using a fetal sheep xenogeneic transplant model. CD 34(+) cells were selected from CB products and cultured in a two-step procedure in the presence of stem cell factor, megakaryocyte growth and differentiation factor, and granulocyte colony-stimulating factor for 14 days. Starting cells (CD34(+) cells), and cultured cells (day 7 and day 14 cells) were transplanted in 60-day-old fetal sheep and evaluated at various time points post transplant for the presence of human cells. Long-term engrafting cells were assessed by serial passage into secondary and tertiary recipients. Day 14 expanded CB cells provided more rapid engraftment than either the day 7 expanded cells or the day 0 cells; however, this engraftment was transient, and no human cells were detectable at 16 months post transplant in the animals that received the day 14 expanded cells. Day 0 cells had engrafted animals at 2 months post transplant and both the day 0 and day 7 cells persisted to 16 months or longer. In the secondary animals, the day 0 and day 7 cells engrafted equivalently at 3 months post transplant; however, no secondary engraftment resulted from the day 14 cells. The levels of engraftment in secondary animals receiving day 7 cells

Labor induction just after external cephalic version with epidural analgesia at term.

PubMed

Cuerva, Marcos J; Piñel, Carlos S; Caceres, Javier; Espinosa, Jose A

2017-06-01

To analyze the benefits of external cephalic version (ECV) with epidural analgesia at term and labor induction just after the procedure. This is a retrospective observational study with patients who did not want trying a breech vaginal delivery and decided trying an ECV with epidural analgesia at term and wanted labor induction or cesarean section after the procedure. We present the results of 40 ECV with epidural analgesia at term and labor induction or cesarean section just after the ECV. ECV succeeded in 26 out of 40 (65%) patients. Among the 26 successful ECV, 6 delivered by cesarean (23.1%). 20 patients delivered vaginally (76.9%; 50% of all patients). Considering that a high number of cesarean deliveries can be avoided, induction of labor after ECV with epidural analgesia at term can be considered after being discussed in selected patient. Copyright © 2017. Published by Elsevier B.V.

High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake.

PubMed

Byerly, Mardi S; Fox, Edward A

2006-06-12

Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.

Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity.

PubMed

Croft, Wayne; Dobson, Katharine L; Bellamy, Tomas C

2015-01-01

The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes) have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours) rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.

The APP-Interacting Protein FE65 is Required for Hippocampus-Dependent Learning and Long-Term Potentiation

ERIC Educational Resources Information Center

Wang, Yan; Zhang, Ming; Moon, Changjong; Hu, Qubai; Wang, Baiping; Martin, George; Sun, Zhongsheng; Wang, Hongbing

2009-01-01

FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of [beta]-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65[superscript -/-]) mice. When examined using the Morris water maze,…

FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and de novo GluA2 Translation

PubMed Central

Jones, Emma V.; Altimimi, Haider F.; Farmer, W. Todd; Gandin, Valentina; Hanna, Edith; Zong, Ruiting; Barbon, Alessandro; Nelson, David L.; Topisirovic, Ivan; Rochford, Joseph; Stellwagen, David; Béïque, Jean-Claude; Murai, Keith K.

2014-01-01

SUMMARY Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression, changes that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in non-neuronal cells and co-localizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase LTP (L-LTP) and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5’UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 incorporated at potentiated synapses. This study uncovers a new mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity. PMID:25456134

Role of Proteasome-Dependent Protein Degradation in Long-Term Operant Memory in "Aplysia"

ERIC Educational Resources Information Center

Lyons, Lisa C.; Gardner, Jacob S.; Gandour, Catherine E.; Krishnan, Harini C.

2017-01-01

We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in "Aplysia" using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through…

Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn

USDA-ARS?s Scientific Manuscript database

Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emis-sions, and global warming potential (GWP) in irrigated systems, however,...

A Single Brief Burst Induces GluR1-Dependent Associative Short-Term Potentiation: A Potential Mechanism for Short-Term Memory

ERIC Educational Resources Information Center

Erickson, Martha A.; Maramara, Lauren A.; Lisman, John

2010-01-01

Recent work showed that short-term memory (STM) is selectively reduced in GluR1 knockout mice. This raises the possibility that a form of synaptic modification dependent on GluR1 might underlie STM. Studies of synaptic plasticity have shown that stimuli too weak to induce long-term potentiation induce short-term potentiation (STP), a phenomenon…

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.

Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins.

PubMed

Nahuis, M J; Kose, N; Bayram, N; van Dessel, H J H M; Braat, D D M; Hamilton, C J C M; Hompes, P G A; Bossuyt, P M; Mol, B W J; van der Veen, F; van Wely, M

2011-07-01

Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these treatments until 8-12 years after their initial treatment. Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a randomized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH. In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity. Analysis was by intention-to-treat. We compared time to conception resulting in live birth, subsequent pregnancies, ectopic and multiple pregnancies, menopause, as well as minimal and maximal menstrual cycle length. After 8-12 years, the cumulative proportion of women with a first child was 86% in women who had been allocated to electrocautery versus 81% in women who had been allocated to immediate rFSH [relative ratio (RR): 1.1; 95% confidence interval (CI): 0.92-1.2]. Treatment with electrocautery resulted in a significantly lower need for stimulated cycles to reach a live birth; 53% after electrocautery versus 76% after rFSH (RR: 0.69; 95% CI: 0.55-0.88).The cumulative proportion of women with a second child was 61% after electrocautery versus 46% after immediate rFSH (RR: 1.4; 95% CI: 1.00-1.9). Overall, there were 7 twins out of 134 deliveries (5%) after electrocautery versus 10 twins out of 124 deliveries (8%) in the rFSH group (RR: 0.65; 95% CI: 0.25-1.6). Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8-12 years after randomization versus 36% in those allocated to rFSH (RR: 1.5; 95% CI: 0.87-2.6). In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births, but reduces

Efficacy of long-term 4.0 g/day mesalazine (Pentasa) for maintenance therapy in ulcerative colitis.

PubMed

Takeshima, Fuminao; Matsumura, Masato; Makiyama, Kazuya; Ohba, Kazuo; Yamakawa, Masaki; Nishiyama, Hitoshi; Yamao, Takuji; Akazawa, Yuko; Yamaguchi, Naoyuki; Ohnita, Ken; Ichikawa, Tatsuki; Isomoto, Hajime; Nakao, Kazuhiko

2014-07-27

High-dose (4.0 g/day) mesalazine is typically used for induction therapy, but its efficacy as maintenance therapy remains to be determined. We conducted a multicenter retrospective study to investigate the efficacy of continuous treatment with 4.0 g/day of mesalazine. Japanese ulcerative colitis (UC) patients receiving acute induction therapy with 4.0 g/day mesalazine were enrolled and followed. Those who clinically improved or who achieved clinical remission were categorized into 2 sub-groups according to the median duration of treatment with 4.0 g/day of mesalazine. The clinical relapse frequency and the time to relapse were analyzed. We enrolled 180 patients with active UC, and then 115 patients who clinically improved or who achieved clinical remission after treatment with 4.0 g/day mesalazine were categorized into 2 sub-groups according to the median of treatment duration: a short-term treatment group (≤105 days, n=58) and a long-term treatment group (>105 days, n=57). Overall, 45 (39.1%) patients relapsed: 28 (48.3%) in the short-term treatment group and 17 (29.8%) in the long-term treatment group. This difference was statistically significant (p<0.05). The relapse-free rate in the long-term treatment group was significantly higher than that in the short-term treatment group (p<0.05). The mean time to relapse in the long-term treatment group was significantly longer than that in the short-term treatment group (425.6±243.8 days vs. 277.4±224.5 days; p<0.05). Long-term continuous treatment with high-dose mesalazine (4.0 g/day) may be more effective than short-term treatment for maintenance of remission in UC patients.

Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

PubMed Central

Tokuda, Kazuhiro; O’Dell, Kazuko A.; Izumi, Yukitoshi; Zorumski, Charles F.

2010-01-01

Benzodiazepines (BDZs) enhance γ-aminobutyric acid-A (GABAA) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors (translocator protein 18kDa, TSPO) and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition following stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA (17-phenyl-(3α, 5α)-androst-16-en-3-ol), a blocker of neurosteroid effects on GABAA receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN, a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated one day prior to midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically-important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity. PMID:21159950

Potential long-term storage of the predatory mite Phytoseiulus persimilis

USDA-ARS?s Scientific Manuscript database

Increasing the ability to store mass-reared natural enemies during periods or seasons of low demand is a critical need of the biocontrol industry. We tested the hypothesis that cryoprotectant or carbohydrate molecules can enhance long-term cold storage of a predatory mite Phytoseiulus persimilis At...

Serum Response Factor (SRF) Ablation Interferes with Acute Stress-Associated Immediate and Long-Term Coping Mechanisms.

PubMed

Zimprich, Annemarie; Mroz, Gabi; Meyer Zu Reckendorf, Christopher; Anastasiadou, Sofia; Förstner, Philip; Garrett, Lillian; Hölter, Sabine M; Becker, Lore; Rozman, Jan; Prehn, Cornelia; Rathkolb, Birgit; Moreth, Kristin; Wurst, Wolfgang; Klopstock, Thomas; Klingenspor, Martin; Adamski, Jerzy; Wolf, Eckhard; Bekeredjian, Raffi; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabe; Knöll, Bernd

2017-12-01

Stress experience modulates behavior, metabolism, and energy expenditure of organisms. One molecular hallmark of an acute stress response is a rapid induction of immediate early genes (IEGs) such as c-Fos and Egr family members. IEG transcription in neurons is mediated by the neuronal activity-driven gene regulator serum response factor (SRF). We show a first role of SRF in immediate and long-lasting acute restraint stress (AS) responses. For this, we employed a standardized mouse phenotyping protocol at the German Mouse Clinic (GMC) including behavioral, metabolic, and cardiologic tests as well as gene expression profiling to analyze the consequences of forebrain-specific SRF deletion in mice exposed to AS. Adult mice with an SRF deletion in glutamatergic neurons (Srf; CaMKIIa-CreERT2 ) showed hyperactivity, decreased anxiety, and impaired working memory. In response to restraint AS, instant stress reactivity including locomotor behavior and corticosterone induction was impaired in Srf mutant mice. Interestingly, even several weeks after previous AS exposure, SRF-deficient mice showed long-lasting AS-associated changes including altered locomotion, metabolism, energy expenditure, and cardiovascular changes. This suggests a requirement of SRF for mediating long-term stress coping mechanisms in wild-type mice. SRF ablation decreased AS-mediated IEG induction and activity of the actin severing protein cofilin. In summary, our data suggest an SRF function in immediate AS reactions and long-term post-stress-associated coping mechanisms.

Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice

PubMed Central

Diaz-Castroverde, Sabela; Gómez-Hernández, Almudena; Fernández, Silvia; García-Gómez, Gema; Di Scala, Marianna; González-Aseguinolaza, Gloria; Fernández-Millán, Elisa; González-Rodríguez, Águeda; García-Bravo, María; Chambon, Pierre; Álvarez, Carmen; Perdomo, Liliana; Beneit, Nuria; Benito, Manuel

2016-01-01

ABSTRACT Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte­-specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus. PMID:27562101

Dynamical model of long-term synaptic plasticity

PubMed Central

Abarbanel, Henry D. I.; Huerta, R.; Rabinovich, M. I.

2002-01-01

Long-term synaptic plasticity leading to enhancement in synaptic efficacy (long-term potentiation, LTP) or decrease in synaptic efficacy (long-term depression, LTD) is widely regarded as underlying learning and memory in nervous systems. LTP and LTD at excitatory neuronal synapses are observed to be induced by precise timing of pre- and postsynaptic events. Modification of synaptic transmission in long-term plasticity is a complex process involving many pathways; for example, it is also known that both forms of synaptic plasticity can be induced by various time courses of Ca2+ introduction into the postsynaptic cell. We present a phenomenological description of a two-component process for synaptic plasticity. Our dynamical model reproduces the spike time-dependent plasticity of excitatory synapses as a function of relative timing between pre- and postsynaptic events, as observed in recent experiments. The model accounts for LTP and LTD when the postsynaptic cell is voltage clamped and depolarized (LTP) or hyperpolarized (LTD) and no postsynaptic action potentials are evoked. We are also able to connect our model with the Bienenstock, Cooper, and Munro rule. We give model predictions for changes in synaptic strength when periodic spike trains of varying frequency and Poisson distributed spike trains with varying average frequency are presented pre- and postsynaptically. When the frequency of spike presentation exceeds ≈30–40 Hz, only LTP is induced. PMID:12114531

ATO/ATRA/anthracycline-chemotherapy sequential consolidation achieves long-term efficacy in primary acute promyelocytic leukemia.

PubMed

Long, Zi-Jie; Hu, Yuan; Li, Xu-Dong; He, Yi; Xiao, Ruo-Zhi; Fang, Zhi-Gang; Wang, Dong-Ning; Liu, Jia-Jun; Yan, Jin-Song; Huang, Ren-Wei; Lin, Dong-Jun; Liu, Quentin

2014-01-01

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4% ± 3.9% and 94.6 ± 3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL.

Induction of transplantation tolerance to fully mismatched cardiac allografts by T cell mediated delivery of alloantigen

PubMed Central

Tian, Chaorui; Yuan, Xueli; Jindra, Peter T.; Bagley, Jessamyn; Sayegh, Mohamed H.; Iacomini, John

2010-01-01

Induction of transplantation tolerance has the potential to allow for allograft acceptance without the need for life-long immunosuppression. Here we describe a novel approach that uses delivery of alloantigen by mature T cells to induce tolerance to fully allogeneic cardiac grafts. Adoptive transfer of mature alloantigen-expressing T cells into myeloablatively conditioned mice results in long-term acceptance of fully allogeneic heart transplants without evidence of chronic rejection. Since myeloablative conditioning is clinically undesirable we further demonstrated that adoptive transfer of mature alloantigen-expressing T cells alone into mice receiving non-myeloablative conditioning resulted in long-term acceptance of fully allogeneic heart allografts with minimal evidence of chronic rejection. Mechanistically, tolerance induction involved both deletion of donor-reactive host T cells and the development of regulatory T cells. Thus, delivery of alloantigen by mature T cells induces tolerance to fully allogeneic organ allografts in non-myeloablatively conditioned recipients, representing a novel approach for tolerance induction in transplantation. PMID:20452826

Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

PubMed

Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

2017-01-01

In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Role of long-term potentiation in mechanism of the conditioned learning].

PubMed

Tsvetkov, E A; Suderevskaia, E I; Veselkin, N P

2011-01-01

The review analyzes the fundamental problem of study of the neuronal mechanisms underlying processes of learning and memory. As a neuronal models of these phenomena there was considered one of the cellular phenomena that has characteristics similar with those in the process of "remembering"--such as the long-term potentiation (LTP). LTP is easily reproduced in certain synapses of the central nervous system, specifically in synapses of hippocampus and amygdala. As to the behavioral model of learning, there was used the conditioned learning, in frames of which production of the context-dependent/independent conditioned reaction was considered. Analysis of literature data has allowed showing that various stages of LTP produced on synapses of hippocampus or amygdala can be comparable with certain phase of the process of learning. Based on the exposed material the authors conclude that plastic changes of synapses of hippocampus and amygdala can represent the morphological substrate of some kinds of learning and memory.

Long-term neurocognitive outcome and auditory event-related potentials after complex febrile seizures in children.

PubMed

Tsai, Min-Lan; Hung, Kun-Long; Tsan, Ying-Ying; Tung, William Tao-Hsin

2015-06-01

Whether prolonged or complex febrile seizures (FS) produce long-term injury to the hippocampus is a critical question concerning the neurocognitive outcome of these seizures. Long-term event-related evoked potential (ERP) recording from the scalp is a noninvasive technique reflecting the sensory and cognitive processes associated with attention tasks. This study aimed to investigate the long-term outcome of neurocognitive and attention functions and evaluated auditory event-related potentials in children who have experienced complex FS in comparison with other types of FS. One hundred and forty-seven children aged more than 6 years who had experienced complex FS, simple single FS, simple recurrent FS, or afebrile seizures (AFS) after FS and age-matched healthy controls were enrolled. Patients were evaluated with Wechsler Intelligence Scale for Children (WISC; Chinese WISC-IV) scores, behavior test scores (Chinese version of Conners' continuous performance test, CPT II V.5), and behavior rating scales. Auditory ERPs were recorded in each patient. Patients who had experienced complex FS exhibited significantly lower full-scale intelligence quotient (FSIQ), perceptual reasoning index, and working memory index scores than did the control group but did not show significant differences in CPT scores, behavior rating scales, or ERP latencies and amplitude compared with the other groups with FS. We found a significant decrease in the FSIQ and four indices of the WISC-IV, higher behavior rating scales, a trend of increased CPT II scores, and significantly delayed P300 latency and reduced P300 amplitude in the patients with AFS after FS. We conclude that there is an effect on cognitive function in children who have experienced complex FS and patients who developed AFS after FS. The results indicated that the WISC-IV is more sensitive in detecting cognitive abnormality than ERP. Cognition impairment, including perceptual reasoning and working memory defects, was identified in

Induction of labour for improving birth outcomes for women at or beyond term

PubMed Central

Gülmezoglu, A Metin; Crowther, Caroline A; Middleton, Philippa; Heatley, Emer

2014-01-01

Background As a pregnancy continues beyond term the risks of babies dying inside the womb or in the immediate newborn period increase. Whether a policy of labour induction at a predetermined gestational age can reduce this increased risk is the subject of this review. Objectives To evaluate the benefits and harms of a policy of labour induction at term or post-term compared with awaiting spontaneous labour or later induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2012). Selection criteria Randomised controlled trials conducted in women at or beyond term. The eligible trials were those comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour. Cluster-randomised trials and cross-over trials are not included. Quasi-random allocation schemes such as alternation, case record numbers or open random-number lists were not eligible. Data collection and analysis Two review authors independently assessed trials for inclusion. Two review authors independently assessed trial quality and extracted data. Data were checked for accuracy. Outcomes are analysed in two main categories: gestational age and cervix status. Main results We included 22 trials reporting on 9383 women. The trials were generally at moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths: risk ratio (RR) 0.31, 95% confidence interval (CI) 0.12 to 0.88; 17 trials, 7407 women. There was one perinatal death in the labour induction policy group compared with 13 perinatal deaths in the expectant management group. The number needed to treat to benefit (NNTB) with induction of labour in order to prevent one perinatal death was 410 (95% CI 322 to 1492). For the primary outcome of perinatal death and most other outcomes, no differences between timing of induction subgroups were seen; the majority of trials adopted

Anticipatory eye movements and long-term memory in early infancy.

PubMed

Wong-Kee-You, Audrey M B; Adler, Scott A

2016-11-01

Advances in our understanding of long-term memory in early infancy have been made possible by studies that have used the Rovee-Collier's mobile conjugate reinforcement paradigm and its variants. One function that has been attributed to long-term memory is the formation of expectations (Rovee-Collier & Hayne, 1987); consequently, a long-term memory representation should be established during expectation formation. To examine this prediction and potentially open the door on a new paradigm for exploring infants' long-term memory, using the Visual Expectation Paradigm (Haith, Hazan, & Goodman, 1988), 3-month-old infants were trained to form an expectation for predictable color and spatial information of picture events and emit anticipatory eye movements to those events. One day later, infants' anticipatory eye movements decreased in number relative to the end of training when the predictable colors were changed but not when the spatial location of the predictable color events was changed. These findings confirm that information encoded during expectation formation are stored in long-term memory, as hypothesized by Rovee-Collier and colleagues. Further, this research suggests that eye movements are potentially viable measures of long-term memory in infancy, providing confirmatory evidence for early mnemonic processes. © 2016 Wiley Periodicals, Inc.

Potential breeding distributions of U.S. birds predicted with both short-term variability and long-term average climate data

Treesearch

Brooke L. Bateman; Anna M. Pidgeon; Volker C. Radeloff; Curtis H. Flather; Jeremy VanDerWal; H. Resit Akcakaya; Wayne E. Thogmartin; Thomas P. Albright; Stephen J. Vavrus; Patricia J. Heglund

2016-01-01

Climate conditions, such as temperature or precipitation, averaged over several decades strongly affect species distributions, as evidenced by experimental results and a plethora of models demonstrating statistical relations between species occurrences and long-term climate averages. However, long-term averages can conceal climate changes that have occurred in...

Clinical trials with rasagiline: evidence for short-term and long-term effects.

PubMed

Siderowf, Andrew; Stern, Matthew

2006-05-23

Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

Group long-term care insurance: decision-making factors and implications for financing long-term care.

PubMed

Stum, Marlene S

2008-01-01

This study proposes and tests a systemic family decision-making framework to understand group long-term care insurance (LTCI) enrollment decisions. A random sample of public employees who were offered group LTCI as a workplace benefit were examined. Findings reveal very good predictive efficacy for the overall conceptual framework with a pseudo R2 value of .687, and reinforced the contributions of factors within the family system. Enrollees were more likely to have discussed the decision with others, used information sources, and had prior experience when compared to non-enrollees. Perceived health status, financial knowledge, attitudes regarding the role of private insurance, risk taking, and coverage features were additional factors related to enrollment decisions. The findings help to inform policymakers about the potential of LTCI as one strategy for financing long-term care.

Using OpenTarget to Generate Potential Countermeasures for Long-Term Space Exposure from Data Available on GeneLab

NASA Technical Reports Server (NTRS)

Beheshti, Afshin

2018-01-01

GeneLab as a general tool for the scientific community; Utilizing GeneLab datasets to generate hypothesis and determining potential biological targets against health risks due to long-term space missions; How can OpenTarget be used to discover novel drugs to test as countermeasures that can be utilized by astronauts.

The expression of long-term potentiation: reconciling the preists and the postivists

PubMed Central

MacDougall, Matthew J.; Fine, Alan

2014-01-01

Long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus has been investigated in great detail over the past 40 years. Where and how LTP is actually expressed, however, remain controversial issues. Considerable evidence has been offered to support both pre- and postsynaptic contributions to LTP expression. Though it is widely held that postsynaptic expression mechanisms are the primary contributors to LTP expression, evidence for that conclusion is amenable to alternative explanations. Here, we briefly review some key contributions to the ‘locus’ debate and describe data that support a dominant role for presynaptic mechanisms. Recognition of the state-dependency of expression mechanisms, and consideration of the consequences of the spatial relationship between postsynaptic glutamate receptors and presynaptic vesicular release sites, lead to a model that may reconcile views from both sides of the synapse. PMID:24298138

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

estuaries below by removing all incoming freshwater. At Toolik Lake, long-term experiments of removing top predators from the good web of lakes showed dramatic alterations of lake populations of small fish and zooplankton. In New Mexico, LTER research on small mammal populations is successfully predicting rodent increases and the potential for increased zoonotic diseases such as Hantavirus and bubonic plague. This ability to forecast based on El Nino prediction is being used to increase scientific awareness and public health awareness through media based communication with the public. In Oregon, the Andrews Forest LTER program has had long, strong links with natural resource policy and management. Basic understanding of forest-stream interactions, characteristics of old-growth forests, roles of woody debris in temperate forest ecosystems, invertebrate biodiversity and ecosystem function have been incorporated in management guidelines, plans and regulations for public and private lands throughout the Pacific Northwest. Other examples of the values of long-term research and monitoring will be presented.

Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis.

PubMed

Tokuda, Kazuhiro; O'Dell, Kazuko A; Izumi, Yukitoshi; Zorumski, Charles F

2010-12-15

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.

Planning for Long-Term Follow-Up: Strategies Learned from Longitudinal Studies.

PubMed

Hill, Karl G; Woodward, Danielle; Woelfel, Tiffany; Hawkins, J David; Green, Sara

2016-10-01

Preventive interventions are often designed and tested with the immediate program period in mind, and little thought that the intervention sample might be followed up for years or even decades beyond the initial trial. However, depending on the type of intervention and the nature of the outcomes, long-term follow-up may well be appropriate. The advantages of long-term follow-up of preventive interventions are discussed and include the capacity to examine program effects across multiple later life outcomes, the ability to examine the etiological processes involved in the development of the outcomes of interest, and the ability to provide more concrete estimates of the relative benefits and costs of an intervention. In addition, researchers have identified potential methodological risks of long-term follow-up such as inflation of type 1 error through post hoc selection of outcomes, selection bias, and problems stemming from attrition over time. The present paper presents a set of seven recommendations for the design or evaluation of studies for potential long-term follow-up organized under four areas: Intervention Logic Model, Developmental Theory and Measurement Issues; Design for Retention; Dealing with Missing Data; and Unique Considerations for Intervention Studies. These recommendations include conceptual considerations in the design of a study, pragmatic concerns in the design and implementation of the data collection for long-term follow-up, as well as criteria to be considered for the evaluation of an existing intervention for potential for long-term follow-up. Concrete examples from existing intervention studies that have been followed up over the long term are provided.

Planning for Long-Term Follow-up: Strategies Learned from Longitudinal Studies

PubMed Central

Hill, Karl G.; Woodward, Danielle; Woelfel, Tiffany; Hawkins, J. David; Green, Sara

2017-01-01

Preventive interventions are often designed and tested with the immediate program period in mind, and little thought that the intervention sample might be followed up for years, or even decades beyond the initial trial. However, depending on the type of intervention and the nature of the outcomes, long-term follow-up may well be appropriate. The advantages of long-term follow-up of preventive interventions are discussed, and include the capacity to examine program effects across multiple later life outcomes, the ability to examine the etiological processes involved in the development of the outcomes of interest and the ability to provide more concrete estimates of the relative benefits and costs of an intervention. In addition, researchers have identified potential methodological risks of long-term follow-up such as inflation of type 1 error through post-hoc selection of outcomes, selection bias and problems stemming from attrition over time. The present paper presents a set of seven recommendations for the design or evaluation of studies for potential long-term follow-up organized under four areas: Intervention Logic Model, Developmental Theory and Measurement Issues; Design for Retention; Dealing with Missing Data; and Unique Considerations for Intervention Studies. These recommendations include conceptual considerations in the design of a study, pragmatic concerns in the design and implementation of the data collection for long-term follow-up, as well as criteria to be considered for the evaluation of an existing intervention for potential for long-term follow-up. Concrete examples from existing intervention studies that have been followed up over the long-term are provided. PMID:26453453

Long-term ecological research in a human-dominated world

Treesearch

G. Philip Robertson; Scott L. Collins; David R. Foster; Nicholas Brokaw; Hugh W. Ducklow; Ted L. Gragson; Corinna Gries; Stephen K. Hamilton; A. David McGuire; John C. Moore; Emily H. Stanley; Robert B. Waide; Mark W. Williams

2012-01-01

The US Long Term Ecological Research (LTER) Network enters its fourth decade with a distinguished record of achievement in ecological science. The value of long-term observations and experiments has never been more important for testing ecological theory and for addressing today’s most difficult environmental challenges. The network’s potential for tackling emergent...

Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.

PubMed

Wright, Brandon J; Jackson, Meyer B

2014-07-16

The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information. Theta burst stimulation of the perforant path potentiated responses throughout the molecular layer, but left responses in the CA3 region unchanged. By contrast, theta burst stimulation of the granule cell layer potentiated responses throughout the molecular layer, as well as in the CA3 region. Theta burst stimulation of the granule cell layer potentiated CA3 responses not only to granule cell layer stimulation but also to perforant path stimulation. Potentiation of responses in the CA3 region reflected NMDA receptor-dependent LTP of upstream synapses between granule cells and mossy cells, with no detectable contribution from NMDA receptor-independent LTP of local CA3 mossy fiber synapses. Potentiation of transmission to the CA3 region required LTP in both granule cell→mossy cell and mossy cell→granule cell synapses. This bidirectional plasticity enables hilar circuitry to regulate the flow of information through the dentate gyrus and on to the hippocampus. Copyright © 2014 the authors 0270-6474/14/349743-11$15.00/0.

Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

PubMed

Mondaca, Mauricio; Hernández, Alejandro; Pérez, Hernán; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Soto-Moyano, Rubén

2004-09-24

Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

Long-term stability of nanostructured thin film electrodes at operating potentials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahluwalia, Rajesh K.; Peng, J. -K.; Wang, X.

Long-term stability of nanostructured thin film (NSTF) catalysts at operating potentials has been investigated. Compared to high surface area Pt/C catalysts, NSTF electrodes show 20–50x smaller F – emission rates (FER) because of their high specific activity for oxygen reduction reaction (ORR), but are susceptible to poisoning by the products of membrane degradation because of their low electrochemically active surface area (ECSA). The observed voltage degradation rates at potentials corresponding to 1–1.5 A/cm 2 current density are much higher than the allowable 13–14 μV/h. Although F – is not itself responsible for performance decay, cumulative fluoride release (CFR) is amore » good marker for catalyst surface contamination. The observed performance decay is not only due to loss of active Pt sites but also adsorbed impurities impeding ORR kinetics. There is a strong correlation between measured CFR and observed decrease in specific ORR activity and limiting current density and increase in mass transfer overpotentials. Furthermore, the correlations indicate that the target of <10% lifetime performance degradation can be achieved by restricting CFR in NSTF electrodes to 0.7 μg/cm 2, as may be possible with more stable membranes, higher surface area NSTF catalysts, and cell operation at lower temperatures and higher relative humidities.« less

Long-term stability of nanostructured thin film electrodes at operating potentials

DOE PAGES

Ahluwalia, Rajesh K.; Peng, J. -K.; Wang, X.; ...

2017-02-09

Long-term stability of nanostructured thin film (NSTF) catalysts at operating potentials has been investigated. Compared to high surface area Pt/C catalysts, NSTF electrodes show 20–50x smaller F – emission rates (FER) because of their high specific activity for oxygen reduction reaction (ORR), but are susceptible to poisoning by the products of membrane degradation because of their low electrochemically active surface area (ECSA). The observed voltage degradation rates at potentials corresponding to 1–1.5 A/cm 2 current density are much higher than the allowable 13–14 μV/h. Although F – is not itself responsible for performance decay, cumulative fluoride release (CFR) is amore » good marker for catalyst surface contamination. The observed performance decay is not only due to loss of active Pt sites but also adsorbed impurities impeding ORR kinetics. There is a strong correlation between measured CFR and observed decrease in specific ORR activity and limiting current density and increase in mass transfer overpotentials. Furthermore, the correlations indicate that the target of <10% lifetime performance degradation can be achieved by restricting CFR in NSTF electrodes to 0.7 μg/cm 2, as may be possible with more stable membranes, higher surface area NSTF catalysts, and cell operation at lower temperatures and higher relative humidities.« less

[Long-term psychiatric hospitalizations].

PubMed

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Loganin enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

PubMed

Hwang, Eun-Sang; Kim, Hyun-Bum; Lee, Seok; Kim, Min-Ji; Lee, Sung-Ok; Han, Seung-Moo; Maeng, Sungho; Park, Ji-Ho

2017-03-15

Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied. Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinalis et Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine. However, there has been limited information available on how loganin affects learning and memory both electrophysiologically and behaviorally. To assess its effect on learning and memory, we investigated the influence of acute loganin administration on long-term potentiation (LTP) using organotypic cultured hippocampal tissues. In addition, we measured the effects of loganin on the behavior performance related to avoidance memory, short-term spatial navigation memory and long-term spatial learning and memory in the passive avoidance, Y-maze, and Morris water maze learning paradigms, respectively. Loganin dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In accordance with these findings, loganin behaviorally attenuated scopolamine-induced shortening of step-through latency in the passive avoidance test, reduced the percent alternation in the Y-maze, and increased memory retention in the Morris water maze test. These results indicate that loganin can effectively block cholinergic muscarinic receptor blockade -induced deterioration of LTP and memory related behavioral performance. Based on these findings, loganin may aid in the prevention and treatment of Alzheimer's disease and learning and memory-deficit disorders in the future. Copyright © 2017 Elsevier

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

PubMed

Centonze, D; Siracusano, A; Calabresi, P; Bernardi, G

2005-01-01

Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

PubMed

Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

2017-03-01

Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.

PubMed

Duintjer Tebbens, Radboud J; Thompson, Kimberly M

2016-12-01

To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

Short-term and long-term plasticity interaction in human primary motor cortex.

PubMed

Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

2011-05-01

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Disparities in long-term care: building equity into market-based reforms.

PubMed

Konetzka, R Tamara; Werner, Rachel M

2009-10-01

A growing body of evidence documents pervasive racial, ethnic, and class disparities in long-term care in the United States. At the same time, major quality improvement initiatives are being implemented that rely on market-based incentives, many of which may have the unintended consequence of exacerbating disparities. We review existing evidence on disparities in the use and quality of long-term care services, analyze current market-based policy initiatives in terms of their potential to ameliorate or exacerbate these disparities, and suggest policies and policy modifications that may help decrease disparities. We find that racial disparities in the use of formal long-term care have decreased over time. Disparities in quality of care are more consistently documented and appear to be related to racial and socioeconomic segregation of long-term care facilities as opposed to within-provider discrimination. Market-based incentives policies should explicitly incorporate the goal of mitigating the potential unintended consequence of increased disparities.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

PubMed

Takeda, Atsushi; Itagaki, Kosuke; Ando, Masaki; Oku, Naoto

2012-03-01

Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. Copyright © 2011 Wiley Periodicals, Inc.

The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats.

PubMed

Pöschel, Beatrice; Wroblewska, Barbara; Heinemann, Uwe; Manahan-Vaughan, Denise

2005-09-01

Group II metabotropic glutamate receptors (mGluRs) play an important role in the regulation of hippocampal synaptic plasticity in vivo: long-term potentiation (LTP) is inhibited and long-term depression (LTD) is enhanced by activation of these receptors. The contribution, in vivo, of the individual group II mGluR subtypes has not been characterized. We analysed the involvement of the subtype mGluR3 in LTD and LTP. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Neither the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), nor the antagonist beta-NAAG, given intracerebrally, affected basal synaptic transmission. beta-NAAG significantly inhibited LTD expression. NAAG exhibited transient inhibitory effects on the intermediate phase of LTD. Whereas NAAG altered paired-pulse responses, beta-NAAG had no effect, suggesting that antagonism of mGluR3 prevents LTD via a postsynaptic mechanism, whereas agonist activation of mGluR3 modulates LTD at a presynaptic locus. NAAG impaired the expression of LTP, whereas beta-NAAG had no effect. NAAG effects on LTP were blocked by EGLU, a selective group II mGluR antagonist. Our data suggest an essential role for mGluR3 in LTD, and a modulatory role for mGluR3 in LTP, with effects being mediated by distinct pre- and post-synaptic loci.

The potential use of diisononyl phthalate metabolites hair as biomarkers to assess long-term exposure demonstrated by a rat model.

PubMed

Hsu, Jen-Yi; Ho, Hsin-Hui; Liao, Pao-Chi

2015-01-01

Diisononyl phthalate (DINP) is a widely used industrial plasticizer. People come into contact with this chemical by using plastic products made with it. Human health can be adversely affected by long-term DINP exposure. However, because the body rapidly excretes DINP metabolites, the use of single-point urine analysis to assess long-term exposure may produce inconsistent results in epidemiologic studies. Hair analysis has a useful place in biomonitoring, particularly in estimating long-term or historical exposure for some chemicals. Several studies have reported using hair analysis to assess the concentrations of heavy metals, drugs and organic pollutants in humans. As a biomarker, DINP metabolites were measured in rat hair in animal experiments to evaluated long-term exposure to DINP. In addition, we evaluated the correlation between the levels of DINP metabolites in hair and in urine. The levels of DINP metabolites in rat hair were significantly higher in the exposure group, relative to the control group (p<0.05). DINP metabolites had a positive correlation with increasing administered dose. Significant positive correlations for MINP, MOINP and MHINP were found between hair and urine (r=0.86, r=0.79 and r=0.74, respectively, p<0.05). Several metabolites in urine showed earlier saturation than in hair. In this report, we detected eight metabolites in hair and demonstrate that hair analysis has potential applications in the assessment of long-term exposure to DINP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of visual experience on developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei.

PubMed

Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Pettorossi, Vito Enrico

2004-11-01

The influence of visual experience deprivation on changes in synaptic plasticity during postnatal development was studied in the ventral part of the rat medial vestibular nuclei (vMVN). We analysed the differences in the occurrence, expressed as a percentage, of long-term depression (LTD) and long-term potentiation (LTP) induced by high frequency stimulation (HFS) of the primary vestibular afferents in rats reared in the light (LR) and those in the dark (DR). In LR rats, HFS only induced LTD in the early stages of development, but the occurrence of LTD progressively decreased to zero before their eyes opened, while that of LTP enhanced from zero to about 50%. Once the rats' eyes had opened, LTD was no longer inducible while LTP occurrence gradually reached the normal adult value (70%). In DR rats, a similar shift from LTD to LTP was observed before their eyes opened, showing only a slightly slower LTD decay and LTP growth, and the LTD annulment was delayed by 1 day. By contrast, the time courses of LTD and LTP development in DR and LR rats showed remarkable differences following eye opening. In fact, LTD occurrence increased to about 50% in a short period of time and remained high until the adult stage. In addition, the occurrence of LTP slowly decreased to less than 20%. The effect of light-deprivation was reversible, since the exposure of DR rats to light, 5 days after eye opening, caused a sudden disappearance of LTD and a partial recover of LTP occurrence. In addition, we observed that a week of light deprivation in LR adult rats did not affect the normal adult LTP occurrence. These results provide evidence that in a critical period of development visual input plays a crucial role in shaping synaptic plasticity of the vMVN, and suggest that the visual guided shift from LTD to LTP during development may be necessary to refine and consolidate vestibular circuitry.

Influence of visual experience on developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei

PubMed Central

Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Pettorossi, Vito Enrico

2004-01-01

The influence of visual experience deprivation on changes in synaptic plasticity during postnatal development was studied in the ventral part of the rat medial vestibular nuclei (vMVN). We analysed the differences in the occurrence, expressed as a percentage, of long-term depression (LTD) and long-term potentiation (LTP) induced by high frequency stimulation (HFS) of the primary vestibular afferents in rats reared in the light (LR) and those in the dark (DR). In LR rats, HFS only induced LTD in the early stages of development, but the occurrence of LTD progressively decreased to zero before their eyes opened, while that of LTP enhanced from zero to about 50%. Once the rats' eyes had opened, LTD was no longer inducible while LTP occurrence gradually reached the normal adult value (70%). In DR rats, a similar shift from LTD to LTP was observed before their eyes opened, showing only a slightly slower LTD decay and LTP growth, and the LTD annulment was delayed by 1 day. By contrast, the time courses of LTD and LTP development in DR and LR rats showed remarkable differences following eye opening. In fact, LTD occurrence increased to about 50% in a short period of time and remained high until the adult stage. In addition, the occurrence of LTP slowly decreased to less than 20%. The effect of light-deprivation was reversible, since the exposure of DR rats to light, 5 days after eye opening, caused a sudden disappearance of LTD and a partial recover of LTP occurrence. In addition, we observed that a week of light deprivation in LR adult rats did not affect the normal adult LTP occurrence. These results provide evidence that in a critical period of development visual input plays a crucial role in shaping synaptic plasticity of the vMVN, and suggest that the visual guided shift from LTD to LTP during development may be necessary to refine and consolidate vestibular circuitry. PMID:15331680

Underlying Mechanisms of Cooperativity, Input Specificity, and Associativity of Long-Term Potentiation Through a Positive Feedback of Local Protein Synthesis.

PubMed

Hao, Lijie; Yang, Zhuoqin; Lei, Jinzhi

2018-01-01

Long-term potentiation (LTP) is a specific form of activity-dependent synaptic plasticity that is a leading mechanism of learning and memory in mammals. The properties of cooperativity, input specificity, and associativity are essential for LTP; however, the underlying mechanisms are unclear. Here, based on experimentally observed phenomena, we introduce a computational model of synaptic plasticity in a pyramidal cell to explore the mechanisms responsible for the cooperativity, input specificity, and associativity of LTP. The model is based on molecular processes involved in synaptic plasticity and integrates gene expression involved in the regulation of neuronal activity. In the model, we introduce a local positive feedback loop of protein synthesis at each synapse, which is essential for bimodal response and synapse specificity. Bifurcation analysis of the local positive feedback loop of brain-derived neurotrophic factor (BDNF) signaling illustrates the existence of bistability, which is the basis of LTP induction. The local bifurcation diagram provides guidance for the realization of LTP, and the projection of whole system trajectories onto the two-parameter bifurcation diagram confirms the predictions obtained from bifurcation analysis. Moreover, model analysis shows that pre- and postsynaptic components are required to achieve the three properties of LTP. This study provides insights into the mechanisms underlying the cooperativity, input specificity, and associativity of LTP, and the further construction of neural networks for learning and memory.

General practitioners' views on (long-term) prescription and use of problematic and potentially inappropriate medication for oldest-old patients-A qualitative interview study with GPs (CIM-TRIAD study).

PubMed

Pohontsch, Nadine Janis; Heser, Kathrin; Löffler, Antje; Haenisch, Britta; Parker, Debora; Luck, Tobias; Riedel-Heller, Steffi G; Maier, Wolfgang; Jessen, Frank; Scherer, Martin

2017-02-17

Potentially inappropriate medication (PIM) is defined as medication with uncertain therapeutic effects and/or potential adverse drug reactions outweighing the clinical benefits. The prescription rate of PIM for oldest-old patients is high despite the existence of lists of PIM (e.g. the PRISCUS list) and efforts to raise awareness. This study aims at identifying general practitioners' views on PIM and aspects affecting the (long-term) use of PIM. As part of the CIM-TRIAD study, we conducted semi-structured, qualitative interviews with 47 general practitioners, discussing 25 patients with and 22 without PIM (according to the PRISCUS list). The interview guideline included generic and patient-specific questions. Interviews were digitally recorded and transcribed verbatim. We content analyzed the interviews using deductive and inductive category development. The majority of the general practitioners were not aware of the PRISCUS list. Agents deemed potentially inappropriate from the general practitioners' point of view and the PRISCUS list are not completely superimposable. General practitioners named their criteria to identify appropriate medication for elderly patients (e.g. renal function, cognitive state) and emphasized the importance of monitoring. We identified prescription- (e.g. benzodiazepines on alternative private prescription), medication- (e.g. subjective perception that PIM has no alternative), general practitioner- (e.g. general practitioner relies on specialists), patient- (e.g. "demanding high-user", positive subjective benefit-risk-ratio) and system-related aspects (e.g. specialists lacking holistic view, interface problems) related to the (long term) use of PIM. While the PRISCUS list does not seem to play a decisive role in general practice, general practitioners are well aware of risks associated with PIM. Our study identifies some starting points for a safer handling of PIM, e.g. stronger dissemination of the PRISCUS list, better compensation of

Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

PubMed

Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

2017-07-19

High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory. SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

Drug-nutrient interactions in three long-term-care facilities.

PubMed

Lewis, C W; Frongillo, E A; Roe, D A

1995-03-01

To assess the risk of drug-nutrient interactions (DNIs) in three long-term-care facilities. Retrospective audit of charts. Three long-term-care facilities in central New York State. Fifty-three patients selected randomly from each facility. Data were collected from the medical record of each patient for a period of 6 months. A computerized algorithm was used to assess the risk for DNIs. Mean drug use, most frequently consumed drugs, incidence of potential DNIs, and the most commonly observed potential DNIs are reported. In facilities A, B, and C, respectively, patients consumed a mean of 4.86, 4.04, and 5.27 drugs per patient per month and were at risk for a mean of 1.43, 2.69, and 1.43 potential DNIs per patient per month. The most commonly observed potential DNIs were gastrointestinal interactions affecting drug bioavailability and interactions affecting electrolyte status. Patients in long-term-care facilities, who are primarily elderly and chronically ill and who consume multiple medications, are at notable risk for certain DNIs. Efforts need to be made to ensure appropriate pharmacologic and nutrition therapies as well as adequate and timely monitoring of patients in these facilities. Dietitians can play an important role in training other health professionals and in designing policies to prevent DNIs.

Rescue of impaired late-phase long-term depression in a tau transgenic mouse model.

PubMed

Ahmed, Tariq; Blum, David; Burnouf, Sylvie; Demeyer, Dominique; Buée-Scherrer, Valérie; D'Hooge, Rudi; Buée, Luc; Balschun, Detlef

2015-02-01

Cognitive decline, the hallmark of Alzheimer's disease, and accompanying neuropsychiatric symptoms share dysfunctions of synaptic processes as a common cellular pathomechanism. Long-term potentiation has proven to be a sensitive tool for the "diagnosis" of such synaptic dysfunctions. Much less, however, is known about how long-term depression (LTD), an alternative mechanism for the storage of memory, is affected by Alzheimer's disease progression. Here, we demonstrate that impaired late LTD (>3 hours) in THY-Tau22 mice can be rescued by either inhibition of glycogen synthase kinase-3 (GSK3β) activity or by application of the protein-phosphatase 2A agonist selenate. In line with these findings, we observed increased phosphorylation of GSK3β at Y216 and reduced total phosphatase activity in biochemical assays of hippocampal tissue of THY-Tau22 mice. Interestingly, LTD induction and pharmacologic inhibition of GSK3β appeared to downregulate GSK3ß activity via a marked upregulation of phosphorylation at the inhibitory Ser9 residue. Our results point to alterations in phosphorylation and/or dephosphorylation homeostasis as key mechanisms underlying the deficits in LTD and hippocampus-dependent learning found in THY-Tau22 mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term Morbidity of Testicular Cancer Treatment.

PubMed

Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

2015-08-01

Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-Term Care Financing: Lessons From France

PubMed Central

Doty, Pamela; Nadash, Pamela; Racco, Nathalie

2015-01-01

Context An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States’ long-term care financing reform efforts. Methods We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. Findings France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income adjusted and amounts are low. Nevertheless, expenditures have exceeded projections, burdening local governments. Private supplemental insurance covers 11% of French, mostly middle-income adults (versus 3% of Americans 18 and older). Whether policyholders will maintain employer-sponsored coverage after retirement is not known. The government's interest in pursuing an explicit public/private partnership has waned under President François Hollande, a centrist socialist, in contrast to the previous center-right leader, President Nicolas Sarkozy, thereby reducing the prospects of a coordinated public/private strategy. Conclusions American private insurers are showing increasing interest in long-term

What's the Rush? Tort Laws and Elective Early-term Induction of Labor.

PubMed

Roth, Louise Marie

2016-12-01

Tort laws aim to deter risky medical practices and increase accountability for harm. This research examines their effects on deterrence of a high-risk obstetric practice in the United States: elective early-term (37-38 weeks gestation) induction of labor. Using birth certificate data from the Natality Detail Files and state-level data from publicly available sources, this study analyzes the effects of tort laws on labor induction with multilevel models (MLM) of 665,491 early-term births nested in states. Results reveal that caps on damages are associated with significantly higher odds of early-term induction and Proportionate Liability (PL) is associated with significantly lower odds compared to Joint and Several Liability (JSL). The findings suggest that clinicians are more likely to engage in practices that defy professional guidelines in tort environments with lower legal burdens. I discuss the implications of the findings for patient safety and the deterrence of high-risk practices. © American Sociological Association 2016.

Memantine alters striatal plasticity inducing a shift of synaptic responses toward long-term depression.

PubMed

Mancini, Maria; Ghiglieri, Veronica; Bagetta, Vincenza; Pendolino, Valentina; Vannelli, Anna; Cacace, Fabrizio; Mineo, Desireé; Calabresi, Paolo; Picconi, Barbara

2016-02-01

Memantine is an open channel blocker that antagonizes NMDA receptors reducing the inappropriate calcium (Ca(2+)) influx occurring in presence of moderately increased glutamate levels. At the same time, memantine has the ability to preserve the transient physiological activation of NMDA receptor, essential for learning and memory formation at synaptic level. In the present study we investigated the effects exerted by memantine on striatal synaptic plasticity in rat striatal spiny projection neurons (SPNs). In vitro application of memantine in striatal slices elicited a disruption of long-term potentiation (LTP) induction and maintenance, and revealed, in the majority of the recorded neurons, a long-term depression (LTD), whose amplitude was concentration-dependent (0.3-10 μM). Interestingly, preincubation with the dopamine (DA) D2 receptor antagonist sulpiride (10 μM) prevented memantine-induced LTD and restored LTP. Moreover, the DA D2 agonist quinpirole (10 μM), similarly to memantine, induced LTD in a subgroup of SPNs. In addition, memantine-induced LTD was also prevented by the CB1 endocannabinoid receptor antagonist AM 251 (1 μM). These results suggest that the actions exerted by memantine on striatal synaptic plasticity, and in particular the induction of LTD observed in SPNs, could be attributed to its ability to activate DA D2 receptors. By contrast, blockade of NMDA receptor is not involved in memantine-induced LTD since APV (30 μM) and MK801 (10 μM), two NMDA receptor antagonists, failed to induce this form of synaptic plasticity. Our data indicate that memantine could be used as treatment of neurological disorders in which DA D2 receptor represents a possible therapeutic target. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electrical high-frequency stimulation of the human thoracolumbar fascia evokes long-term potentiation-like pain amplification.

PubMed

Schilder, Andreas; Magerl, Walter; Hoheisel, Ulrich; Klein, Thomas; Treede, Rolf-Detlef

2016-10-01

Nociceptive long-term potentiation, a use dependent increase in synaptic efficacy in the dorsal horn of the spinal cord is thought to contribute to the development of persistent pain states. So far, no study has analyzed the effects of high-frequency stimulation (HFS) of afferents from deep tissues (muscle and fascia) on pain perception in the back in humans. In 16 healthy volunteers, the multifidus muscle and the overlying thoracolumbar fascia were stimulated with electrical high-frequency pulses (5 × 100 pulses at 100 Hz) through bipolar concentric needle electrodes placed at lumbar level (L3/L4). Electrical pain thresholds were lower (P < 0.001) and pain ratings were higher for fascia compared with muscle stimulation (P < 0.05). For both tissues, pain ratings increased significantly across the five 100 Hz trains (from 15 to 22 numerical rating scale for fascia, from 8 to 12 numerical rating scale for muscle; both P < 0.01). Fascia HFS increased fascia pain ratings 2.17 times compared with the unconditioned control site (P < 0.001), but had no significant effect on pain sensitivity of the muscle. The HFS in muscle had no significant effect on muscle pain, but decreased pain sensitivity of the overlying fascia by 20% (P < 0.05). In additional experiments using the same electrodes and followed over >60 minutes post-HFS, potentiation by fascia HFS was similar to that of skin HFS. These findings show that the spinal input from the fascia can induce long-term changes in pain sensitivity for at least 60 minutes making it a candidate potentially contributing to nonspecific low back pain.

Evaluation Effect of Shiatsu Technique on Labor Induction in Post-Term Pregnancy

PubMed Central

Batool, Teimoori; Shahin-Dokht, Navvabi-Rigi; Shahnaz, Rajabi; Azizollah, Arbabisarjou

2015-01-01

Objective: Labor induction in post-term pregnancy is considered as a conventional process of mothers’ care. Shiatsu technique is one of the complementary methods which use for post-term pregnancy induction. Therefore, the researchers decided to examine the effect of Shiatsu technique on the induction of post-term pregnancy. Materials and Methods: This is a randomized control trials which conducted on 288 women with post-term pregnancy who referred to consulting clinic at Ali- Ibn- Abi -Talib Hospital, in Zahedan-Iran in 2010-2011. Participants were selected based on random table. The participants divided into two groups: the first was shiatsu technique and the second group was control group (routine procedure). Shiatsu technique was conducted on the participants of intervention group for 30s on three points by an experienced midwife. The gathered data analyzed by SPSS version 15.00 and comparing tests were t-students tests, chi-square. Results: Mothers ages range were between 16 to 42 yr (mean 26.5-5.7) in shiatsu and 17 to 43 yr (mean 24.5-5.1) in control group. Regarding spontaneous initiation of labor, 82 women (56.9%) in Shiatsu group had spontaneous initiation of labor, whereas the number of women was only 12 (8.3%) in control group. Women who have used Shiatsu technique were significantly more likely to have spontaneous labour than those women who did not. Conclusions: Results of the study showed that shiatsu technique can be used as one of safe complementary methods for post-term pregnancy induction. PMID:25948426

Long-term mobile phone use and acoustic neuroma risk.

PubMed

Pettersson, David; Mathiesen, Tiit; Prochazka, Michaela; Bergenheim, Tommy; Florentzson, Rut; Harder, Henrik; Nyberg, Gunnar; Siesjö, Peter; Feychting, Maria

2014-03-01

There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited. We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%). Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (≥10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (≥680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for ≥680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses. The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term Ecosystem Experiments, Data Assimilation, and Meta-Analysis

NASA Astrophysics Data System (ADS)

Hungate, B. A.; Van Groenigen, K. J.; Osenberg, C. W.; van Gestel, N.

2015-12-01

Land ecosystems affect climate and the atmosphere, and climate and atmospheric change affects ecosystems. Syntheses of ecosystem experiments investigating their responses to environmental change holds promise for understanding how to model these interactions, and thereby gain insight into Earth's future biosphere, atmosphere, and climate. Long-term experiments examining ecosystem responses are thought to be especially important in this effort, for their potential to reveal cumulative and progressive effects, subtle effects initially undetectable experimentally, but manifest more clearly over time, often with stronger implications for modeled responses than the more dramatic, short-term experimental responses. Here, we present new analyses of long-term experiments manipulating temperature, CO2 concentration, and precipitation, testing the general hypothesis that there are common temporal patterns of responses that reveal general biogeochemical characterizing ecosystem responses to these environmental changes. For example, we show that increased carbon input with elevated CO2 stimulates emissions of nitrous oxide and methane, important greenhouse gases, and that effects show no signs of diminishing over the duration of experiments that have documented responses. At the same time, we show that the temporal resolution for this response is limited, pointing to a potential limitation in the ability of experiments to address clearly long-term hypotheses. We also show that warming tends to have limited cumulative effects on total soil carbon stocks in long-term experiments, and explore the mechanisms underlying this response. Finally, we discuss the implications of these findings for models used to simulate long-term ecosystem responses to these environmental forcings, as well as the implications of these findings for the next generation of terrestrial ecosystem experiments.

Distinct Roles of PKCι/λ and PKMζ in the Initiation and Maintenance of Hippocampal Long-Term Potentiation and Memory.

PubMed

Wang, Shaoli; Sheng, Tao; Ren, Siqiang; Tian, Tian; Lu, Wei

2016-08-16

PKMζ has been proposed to be essential for maintenance of long-term potentiation (LTP) and long-term memory (LTM). However, recent data from PKMζ-knockout mice has called this role into question. Instead, the other atypical isoform, protein kinase C iota/lambda (PKCι/λ), has emerged as a potential alternative player. Therefore, the nature of the "memory molecule" maintaining learned information remains uncertain. Here, we report knockdown (KD) of PKCι/λ and PKMζ in the dorsal hippocampus and find deficits in early expression and late maintenance, respectively, during both LTP and hippocampus-dependent LTM. Sequential increases in the active form of PKCι/λ and PKMζ are detected during LTP or fear conditioning. Importantly, PKMζ, but not PKCι/λ, KD disrupts previously established LTM. Thus, PKCι/λ and PKMζ have distinct functions in LTP and memory, with PKMζ playing a specific role in memory maintenance. This relaying pattern may represent a precise molecular mechanism by which atypical PKCs regulate the different stages of memory. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation.

PubMed

Onaivi, Emmanuel S; Ali, Syed F; Chirwa, Sanika S; Zwiller, Jean; Thiriet, Nathalie; Akinshola, B Emmanuel; Ishiguro, Hiroki

2002-06-01

The mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and diseases that have hereditary components. Thus, large-scale, parallel gene-expression studies, made possible by advances in microarray technologies, have shown insights into the connection between specific genes, or sets of genes, and human diseases. The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general is intensively studied. Pharmacological treatment of drug and alcohol addiction has largely been disappointing, and new therapeutic targets and hypotheses are needed. As the usefulness of the pharmacotherapy of addiction has been limited, an emerging potential, yet controversial, therapeutic agent is the natural alkaloid ibogaine. We have continued to investigate programs of gene expression and the putative signaling molecules used by psychostimulants such as amphetamine in in vivo and in vitro models. Our work and that of others reveal that complex but defined signal transduction pathways are associated with psychostimulant administration and that there is broad-spectrum regulation of these signals by ibogaine. We report that the actions of methamphetamine were similar to those of cocaine, including the propensity to alter long-term potentiation (LTP) in the hippocampus of the rat brain. This action suggests that there may be a "threshold" beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP. The influence of ibogaine on immediate early genes (IEGs) and other candidate genes possibly regulated by psychostimulants and other abused substances requires further evaluation in compulsive use, reward, relapse, tolerance, craving and withdrawal reactions. It is therefore tempting to suggest that ibogaine signals addiction gene products.

Effect of climate fluctuation on long-term vegetation dynamics in Carolina bay wetlands

Treesearch

Chrissa Stroh; Diane De Steven; Glenn Guntenspergen

2008-01-01

Carolina bays and similar depression wetlands of the U. S. Southeastern Coastal Plain have hydrologic regimes that are driven primarily by rainfall. Therefore, climate fluctuations such as drought cycles have the potential to shape long-term vegetation dynamics. Models suggest two potential long-term responses to hydrologic fluctuations, either cyclic change...

Sonographical predictive markers of failure of induction of labour in term pregnancy.

PubMed

Brik, Maia; Mateos, Silvia; Fernandez-Buhigas, Irene; Garbayo, Paloma; Costa, Gloria; Santacruz, Belen

2017-02-01

Predictive markers of failure of induction of labour in term pregnancy were evaluated. A prospective study including 245 women attending induction of labour was performed. The inclusion criteria were singleton pregnancies, gestational age 37-42 weeks and the main outcomes were failure of induction, induction to delivery interval and mode of delivery. Women with a longer cervical length prior to induction (CLpi) had a higher rate of failure of induction (30.9 ± 6.8 vs. 23.9 ± 9.3, p < .001). BMI was higher and maternal height was lower in the group of caesarean section compared to vaginal delivery (33.1 ± 8 vs. 29.3 ± 4.6, 160 ± 5 vs. 164 ± 5, p < .001, respectively). A shorter CLpi correlated with a shorter induction to delivery interval (R Pearson .237, p < .001). In the regression analysis, for failure of induction the only independent predictor was the CL prior to induction. Therefore, the CLpi is an independent factor for prediction of failure of induction of labour.

Long-term use of short- and long-acting nitrates in stable angina pectoris.

PubMed

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

PubMed

Zhu, G; Wang, Y; Li, J; Wang, J

2015-04-30

Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A systematic review of potential long-term effects of sport-related concussion

PubMed Central

Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K. Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

2017-01-01

Objective Systematic review of possible long-term effects of sports-related concussion in retired athletes. Data sources Ten electronic databases. Study selection Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. Data extraction Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Results Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Conclusion Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. PMID:28455362

Plastic mulching in agriculture. Trading short-term agronomic benefits for long-term soil degradation?

PubMed

Steinmetz, Zacharias; Wollmann, Claudia; Schaefer, Miriam; Buchmann, Christian; David, Jan; Tröger, Josephine; Muñoz, Katherine; Frör, Oliver; Schaumann, Gabriele Ellen

2016-04-15

Plastic mulching has become a globally applied agricultural practice for its instant economic benefits such as higher yields, earlier harvests, improved fruit quality and increased water-use efficiency. However, knowledge of the sustainability of plastic mulching remains vague in terms of both an environmental and agronomic perspective. This review critically discusses the current understanding of the environmental impact of plastic mulch use by linking knowledge of agricultural benefits and research on the life cycle of plastic mulches with direct and indirect implications for long-term soil quality and ecosystem services. Adverse effects may arise from plastic additives, enhanced pesticide runoff and plastic residues likely to fragment into microplastics but remaining chemically intact and accumulating in soil where they can successively sorb agrochemicals. The quantification of microplastics in soil remains challenging due to the lack of appropriate analytical techniques. The cost and effort of recovering and recycling used mulching films may offset the aforementioned benefits in the long term. However, comparative and long-term agronomic assessments have not yet been conducted. Furthermore, plastic mulches have the potential to alter soil quality by shifting the edaphic biocoenosis (e.g. towards mycotoxigenic fungi), accelerate C/N metabolism eventually depleting soil organic matter stocks, increase soil water repellency and favour the release of greenhouse gases. A substantial process understanding of the interactions between the soil microclimate, water supply and biological activity under plastic mulches is still lacking but required to estimate potential risks for long-term soil quality. Currently, farmers mostly base their decision to apply plastic mulches rather on expected short-term benefits than on the consideration of long-term consequences. Future interdisciplinary research should therefore gain a deeper understanding of the incentives for farmers

Long-term academic stress enhances early processing of facial expressions.

PubMed

Zhang, Liang; Qin, Shaozheng; Yao, Zhuxi; Zhang, Kan; Wu, Jianhui

2016-11-01

Exposure to long-term stress can lead to a variety of emotional and behavioral problems. Although widely investigated, the neural basis of how long-term stress impacts emotional processing in humans remains largely elusive. Using event-related brain potentials (ERPs), we investigated the effects of long-term stress on the neural dynamics of emotionally facial expression processing. Thirty-nine male college students undergoing preparation for a major examination and twenty-one matched controls performed a gender discrimination task for faces displaying angry, happy, and neutral expressions. The results of the Perceived Stress Scale showed that participants in the stress group perceived higher levels of long-term stress relative to the control group. ERP analyses revealed differential effects of long-term stress on two early stages of facial expression processing: 1) long-term stress generally augmented posterior P1 amplitudes to facial stimuli irrespective of expression valence, suggesting that stress can increase sensitization to visual inputs in general, and 2) long-term stress selectively augmented fronto-central P2 amplitudes for angry but not for neutral or positive facial expressions, suggesting that stress may lead to increased attentional prioritization to processing negative emotional stimuli. Together, our findings suggest that long-term stress has profound impacts on the early stages of facial expression processing, with an increase at the very early stage of general information inputs and a subsequent attentional bias toward processing emotionally negative stimuli. Copyright © 2016 Elsevier B.V. All rights reserved.

Synaptic long-term potentiation realized in Pavlov's dog model based on a NiOx-based memristor

NASA Astrophysics Data System (ADS)

Hu, S. G.; Liu, Y.; Liu, Z.; Chen, T. P.; Yu, Q.; Deng, L. J.; Yin, Y.; Hosaka, Sumio

2014-12-01

Synaptic Long-Term Potentiation (LTP), which is a long-lasting enhancement in signal transmission between neurons, is widely considered as the major cellular mechanism during learning and memorization. In this work, a NiOx-based memristor is found to be able to emulate the synaptic LTP. Electrical conductance of the memristor is increased by electrical pulse stimulation and then spontaneously decays towards its initial state, which resembles the synaptic LTP. The lasting time of the LTP in the memristor can be estimated with the relaxation equation, which well describes the conductance decay behavior. The LTP effect of the memristor has a dependence on the stimulation parameters, including pulse height, width, interval, and number of pulses. An artificial network consisting of three neurons and two synapses is constructed to demonstrate the associative learning and LTP behavior in extinction of association in Pavlov's dog experiment.

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis.

PubMed

Dong, Zhifang; Han, Huili; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoyan; Zhou, Weihui; Jin, Wuyang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

2015-01-01

Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer's disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.

Antibiotic Use and Need for Antimicrobial Stewardship in Long-Term Care.

PubMed

Wu, Lisa Dong-Ying; Walker, Sandra A N; Elligsen, Marion; Palmay, Lesley; Simor, Andrew; Daneman, Nick

2015-01-01

Antimicrobial stewardship may be important in long-term care facilities because of unnecessary or inappropriate antibiotic use observed in these residents, coupled with their increased vulnerability to health care-associated infections. To assess antibiotic use in a long-term care facility in order to identify potential antimicrobial stewardship needs. A retrospective descriptive study was conducted at the Veterans Centre, a long-term care facility at Sunnybrook Health Sciences Centre, Toronto, Ontario. All residents taking one or more antibiotics (n = 326) were included as participants. Antibiotic-use data for patients residing in the facility between April 1, 2011, and March 31, 2012, were collected and analyzed. Totals of 358 patient encounters, 835 antibiotic prescriptions, and 193 positive culture results were documented during the study period. For 36% (302/835) of antibiotic prescriptions, the duration was more than 7 days. Cephalosporins (30%; 251/835) and fluoroquinolones (28%; 235/835) were the most frequently prescribed antibiotic classes. Urine was the most common source of samples for culture (60%; 116/193). Characteristics of antimicrobial use at this long-term care facility that might benefit from further evaluation included potentially excessive use of fluoroquinolones and cephalosporins and potentially excessive duration of antibiotic use for individual patients.

Formula for the Transition Probability Induced by Long-range Potential Terms Varying as R-8 and R-10 for Atom-dimer Collisions

NASA Astrophysics Data System (ADS)

Matthews, N. F.; Robson, D.; Grant, M. A.

1990-12-01

An explicit formula is derived for the transition probability between two different states of the atom-dimer collisional system governed by second-order long-range interaction potential terms varying as R-8 and R-10.

The association between long-term care setting and potentially preventable hospitalizations among older dual eligibles.

PubMed

Wysocki, Andrea; Kane, Robert L; Golberstein, Ezra; Dowd, Bryan; Lum, Terry; Shippee, Tetyana

2014-06-01

To compare the probability of experiencing a potentially preventable hospitalization (PPH) between older dual eligible Medicaid home and community-based service (HCBS) users and nursing home residents. Three years of Medicaid and Medicare claims data (2003-2005) from seven states, linked to area characteristics from the Area Resource File. A primary diagnosis of an ambulatory care sensitive condition on the inpatient hospital claim was used to identify PPHs. We used inverse probability of treatment weighting to mitigate the potential selection of HCBS versus nursing home use. The most frequent conditions accounting for PPHs were the same among the HCBS users and nursing home residents and included congestive heart failure, pneumonia, chronic obstructive pulmonary disease, urinary tract infection, and dehydration. Compared to nursing home residents, elderly HCBS users had an increased probability of experiencing both a PPH and a non-PPH. HCBS users' increased probability for potentially and non-PPHs suggests a need for more proactive integration of medical and long-term care. © Health Research and Educational Trust.

HIV-related politics in long-term perspective.

PubMed

Friedman, S R

1998-06-01

Some long-term, large-scale socio-economic changes may affect the politics of HIV and other emerging viruses such as hepatitis C. It is useful to ask why the potential peace dividend of the early 1990s failed to provide adequate resources for HIV-related social and medical service delivery in developed or developing nations. This failure can be understood by looking at long-term global economic trends and the pressures they put on governments and corporations. They have produced a period in which fundamental issues of political and economic structure are at stake and, often, the response is a divide-and-rule politics to promote stability. National politics differ in terms of the extent to which such a 'politics of scapegoating' is institutionalized and in terms of which groups are scapegoated. Groups such as drug injectors, gay and bisexual men and sex traders are particularly likely to be targeted both by the scapegoaters and by HIV. Given this framework, how should public health professionals and activists engaged in HIV-related issues respond? Under what circumstances should we orient efforts upwards towards corporate, political or bureaucratic leaders? Under what circumstances, and how, should we orient towards popular forces? Relatedly, we need to consider an issue we often ignore: What do we have to offer potential allies? That is, in terms of their goals, philosophies and needs, why should they ally with us?

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil's Amazon Rainforest.

PubMed

Guimarães Marques, Marcia J; Reyes-Garcia, Selvin Z; Marques-Carneiro, José E; Lopes-Silva, Leonardo B; Andersen, Monica L; Cavalheiro, Esper A; Scorza, Fulvio A; Scorza, Carla A

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed

Aniracetam attenuates H2O2-induced deficiency of neuron viability, mitochondria potential and hippocampal long-term potentiation of mice in vitro.

PubMed

Wang, Yong-Fu; Li, Chao-Cui; Cai, Jing-Xia

2006-09-01

Objective It is known that free radicals are involved in neurodegeneration and cognitive dysfunction, as seen in Alzheimer' s disease (AD) and aging. The present study examines the protective effects of aniracetam against H2O2-induced toxicity to neuron viability, mitochondria potential and hippocampal long-term potentiation (LTP). Methods Tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was used to detect neuronal viability. MitoTracker Red (CMX Ros), a fluorescent stain for mitochondria, was used to measure mitochondria potential. Electrophysiological technique was carried out to record hippocampal LTP. Results H2O2 exposure impaired the viability of neurons, reduced mitochondria potential, and decreased LTP in the CA1 region of hippocampus. These deficient effects were significantly rescued by pre-treatment with aniracetam (10-100 mu mol/L). Conclusion These results indicate that aniracetam has a strong neuroprotective effect against H2O2-induced toxicity, which could partly explain the mechanism of its clinical application in neurodegenerative diseases.

The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

PubMed

Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2016-04-21

The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher's exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.

Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus

PubMed Central

Dennis, Siobhan H.; Pasqui, Francesca; Colvin, Ellen M.; Sanger, Helen; Mogg, Adrian J.; Felder, Christian C.; Broad, Lisa M.; Fitzjohn, Steve M.; Isaac, John T.R.; Mellor, Jack R.

2016-01-01

Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans. PMID:26472558

Long-term care: The public role and private initiatives

PubMed Central

Burke, Thomas R.

1988-01-01

The ongoing effort of the U.S. Department of Health and Human Services to identify private financing mechanisms that can effectively assist the rapidly growing population of older persons in paying for long-term care expenses is discussed in this article. The focus on private strategies stems from the recognition that Federal and State sectors already pay almost one-half of all long-term care expenses, the proclivity of liberalized financing structures to raise total costs, and the tendency of public financing to dampen choice, flexibility, and access to care. In view of the improved economic situation of most older persons in our Nation today, the potential for market development of private financing options is thought to be excellent, particularly the market for long-term care insurance. PMID:10312961

Attention Problems, Phonological Short-Term Memory, and Visuospatial Short-Term Memory: Differential Effects on Near- and Long-Term Scholastic Achievement

ERIC Educational Resources Information Center

Sarver, Dustin E.; Rapport, Mark D.; Kofler, Michael J.; Scanlan, Sean W.; Raiker, Joseph S.; Altro, Thomas A.; Bolden, Jennifer

2012-01-01

The current study examined individual differences in children's phonological and visuospatial short-term memory as potential mediators of the relationship among attention problems and near- and long-term scholastic achievement. Nested structural equation models revealed that teacher-reported attention problems were associated negatively with…

A systematic review of potential long-term effects of sport-related concussion.

PubMed

Manley, Geoff; Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

2017-06-01

Systematic review of possible long-term effects of sports-related concussion in retired athletes. Ten electronic databases. Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as > 10 years after the injury. Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Long-term urethral catheterisation.

PubMed

Turner, Bruce; Dickens, Nicola

This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

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.

Long-term stable active mount for reflective optics

NASA Astrophysics Data System (ADS)

Reinlein, C.; Brady, A.; Damm, C.; Mohaupt, M.; Kamm, A.; Lange, N.; Goy, M.

2016-07-01

We report on the development of an active mount with an orthogonal actuator matrix offering a stable shape optimization for gratings or mirrors. We introduce the actuator distribution and calculate the accessible Zernike polynomials from their actuator influence function. Experimental tests show the capability of the device to compensate for aberrations of grating substrates as we report measurements of a 110x105 mm2 and 220x210 mm2 device With these devices, we evaluate the position depending aberrations, long-term stability shape results, and temperature-induced shape variations. Therewith we will discuss potential applications in space telescopes and Earth-based facilities where long-term stability is mandatory.

Mechanisms of Translation Control Underlying Long-lasting Synaptic Plasticity and the Consolidation of Long-term Memory

PubMed Central

Santini, Emanuela; Huynh, Thu N.; Klann, Eric

2018-01-01

The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation (LTP). New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation have enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we will discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. PMID:24484700

Long-term care: long-term care insurance--2005. End of Year Issue Brief.

PubMed

Tanner, Rachel; Bercaw, Lawren

2005-12-31

As the "Baby Boom" generation approaches retirement, state and federal lawmakers are struggling to ensure that the nation's long-term care system will provide adequate services for the growing number of senior citizens. A 2003 Administration on Aging report predicted that the elderly population will double by 2030. Accordingly, policymakers must prepare for the impending squeeze on public health and Medicaid resources. Many consumers are exploring private long-term care insurance options as a means of preparing for the cost of eldercare. Yet, a lack of market uniformity has rendered the long-term care insurance industry somewhat difficult for consumers to decipher. In addition, senior care insurance is often costly, particularly for those over age 50.

Long-term prognosis of depression in primary care.

PubMed Central

Simon, G. E.

2000-01-01

This article uses longitudinal data from a primary care sample to examine long-term prognosis of depression. A sample of 225 patients initiating antidepressant treatment in primary care completed assessments of clinical outcome (Hamilton Depression Rating Scale and the mood module of the Structured Clinical Interview for DSM-IIIR) 1, 3, 6, 9, 12, 18 and 24 months after initiating treatment. The proportion of patients continuing to meet criteria for major depression fell rapidly to approximately 10% and remained at approximately that level throughout follow-up. The proportion meeting criteria for remission (Hamilton Depression score of 7 or less) rose gradually to approximately 45%. Long-term prognosis (i.e. probability of remission at 6 months and beyond) was strongly related to remission status at 3 months (odds ratio 3.65; 95% confidence interval, 2.81-4.76) and only modestly related to various clinical characteristics assessed at baseline (e.g. prior history of recurrent depression, medical comorbidity, comorbid anxiety symptoms). The findings indicate that potentially modifiable risk factors influence the long-term prognosis of depression. This suggests that more systematic and effective depression treatment programmes might have an important effect on long-term course and reduce the overall burden of chronic and recurrent depression. PMID:10885162

Long-term bed degradation in Maryland streams (phase 2) : Blue Ridge and Western Piedmont provinces.

DOT National Transportation Integrated Search

2012-03-01

Estimation of potential long-term down-cutting of the stream bed is necessary for evaluation and design of bridges for scour and culverts for fish passage. The purpose of this study has been to improve predictions of this potential long-term bed degr...

Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors.

PubMed

Puyal, Julien; Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Demêmes, Danielle; Raymond, Jaqueline; Pettorossi, Vito Enrico

2003-12-01

The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN.

Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors

PubMed Central

Puyal, Julien; Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Demêmes, Danielle; Raymond, Jaqueline; Pettorossi, Vito Enrico

2003-01-01

The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN. PMID:12972627

Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release.

PubMed

Mereu, Giampaolo; Fà, Mauro; Ferraro, Luca; Cagiano, Raffaele; Antonelli, Tiziana; Tattoli, Maria; Ghiglieri, Veronica; Tanganelli, Sergio; Gessa, Gian Luigi; Cuomo, Vincenzo

2003-04-15

To investigate the possible long-term consequences of gestational exposure to cannabinoids on cognitive functions, pregnant rats were administered with the CB1 receptor agonist WIN 55,212-2 (WIN), at a dose (0.5 mgkg) that causes neither malformations nor overt signs of toxicity. Prenatal WIN exposure induced a disruption of memory retention in 40- and 80-day-old offspring subjected to a passive avoidance task. A hyperactive behavior at the ages of 12 and 40 days was also found. The memory impairment caused by the gestational exposure to WIN was correlated with alterations of hippocampal long-term potentiation (LTP) and glutamate release. LTP induced in CA3-CA1 synapses decayed faster in brain slices of rats born from WIN-treated dams, whereas posttetanic and short-term potentiation were similar to the control group. In line with LTP shortening, in vivo microdialysis showed a significant decrease in basal and K(+)-evoked extracellular glutamate levels in the hippocampus of juvenile and adult rats born from WIN-treated dams. A similar reduction in glutamate outflow was also observed in primary cell cultures of hippocampus obtained from pups born from mothers exposed to WIN. The decrease in hippocampal glutamate outflow appears to be the cause of LTP disruption, which in turn might underlie, at least in part, the long-lasting impairment of cognitive functions caused by the gestational exposure to this cannabinoid agonist. These findings could provide an explanation of cognitive alterations observed in children born from women who use marijuana during pregnancy.

Dying with Dementia in Long-Term Care

ERIC Educational Resources Information Center

Sloane, Philip D.; Zimmerman, Sheryl; Williams, Christianna S.; Hanson, Laura C.

2008-01-01

Purpose: To better understand the experiences and potential unmet need of persons who die in long-term care. Design and Methods: We conducted after-death interviews with staff who had cared for 422 decedents with dementia and 159 who were cognitively intact and received terminal care in U.S. nursing homes (NHs) or residential care-assisted living…

Assessing the associative deficit of older adults in long-term and short-term/working memory.

PubMed

Chen, Tina; Naveh-Benjamin, Moshe

2012-09-01

Older adults exhibit a deficit in associative long-term memory relative to younger adults. However, the literature is inconclusive regarding whether this deficit is attenuated in short-term/working memory. To elucidate the issue, three experiments assessed younger and older adults' item and interitem associative memory and the effects of several variables that might potentially contribute to the inconsistent pattern of results in previous studies. In Experiment 1, participants were tested on item and associative recognition memory with both long-term and short-term retention intervals in a single, continuous recognition paradigm. There was an associative deficit for older adults in the short-term and long-term intervals. Using only short-term intervals, Experiment 2 utilized mixed and blocked test designs to examine the effect of test event salience. Blocking the test did not attenuate the age-related associative deficit seen in the mixed test blocks. Finally, an age-related associative deficit was found in Experiment 3, under both sequential and simultaneous presentation conditions. Even while accounting for some methodological issues, the associative deficit of older adults is evident in short-term/working memory.

Long-term associative learning predicts verbal short-term memory performance.

PubMed

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

Asthma Medicines: Long-Term Control

MedlinePlus

... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

PubMed

Colas, Damien; Chuluun, Bayarsaikhan; Garner, Craig C; Heller, H Craig

2017-04-01

Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABA A receptor (GABA A R) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABA A R antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS. Copyright © 2017. Published by Elsevier Inc.

Ventricular Late Potentials Immediately Post ST-Elevation Myocardial Infarction, and Very Long-Term Mortality.

PubMed

Shturman, Alexander; Vardi, Shira; Bickel, Amitai; Atar, Shaul

2017-04-01

The very long-term prognostic significance of ventricular late potentials (VLP) in patients post ST-elevation myocardial infarction (STEMI) is unclear. To evaluate the long-term predictive value of VLP for mortality post-STEMI. We conducted serial signal-averaged electrocardiography (SAECG) measurements in 63 patients on the 1st, 2nd and 3rd day pre-discharge, and 30 days after STEMI in patients admitted in 2001. We followed the patients for 10 years and correlated the presence of VLP with all-cause and cardiovascular mortality. The mean age was 59.9 ± 12.3 years. Thrombolysis was performed in 41 patients (65%). Percutaneous coronary intervention was performed pre-discharge in 40 patients (63%) and coronary artery bypass grafting in 7 (11%). Five consecutive measurements to define the presence of VLP were obtained in 52 patients (21 with VLP and 31 without). We found a higher prevalence of VLP in males compared to females (QRS segment > 114 msec, 51% vs. 12%, P = 0.02, duration of the low amplitude signal < 40 mV) in the terminal portion of the averaged QRS complex > 38 msec, 47% vs. 25%, P = 0.05). Over 10 years of follow-up, 14 (22%) patients died, 10 (70%) due to cardiovascular non-arrhythmic complications, 6 with VLP compared to only 3 without (28.6% vs. 9.7%, P = 0.125, hazard ratio = 2.96, confidence intervals = 0.74-11.84) (are these numbers meant to total 10?). Over 10 years of follow-up, the presence of VLP in early post-STEMI is not predictive of arrhythmic or non-arrhythmic cardiovascular mortality.

Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials.

PubMed

Morano, Michela; Wrobel, Sandra; Fregnan, Federica; Ziv-Polat, Ofra; Shahar, Abraham; Ratzka, Andreas; Grothe, Claudia; Geuna, Stefano; Haastert-Talini, Kirsten

2014-01-01

Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation. Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs) and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs). The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12) cell sympathetic culture model system. We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12 cell system. Our results evidence that nanotechnology as used in our setup is superior over stem cell engineering when it comes to in vitro models for PNR. Furthermore, np-NTFs can easily be suspended in regenerative hydrogel matrix and could be delivered that way to nerve conduits for future in vivo studies and medical application.

Graphitized Carbon: A Promising Stable Cathode Catalyst Support Material for Long Term PEMFC Applications.

PubMed

Mohanta, Paritosh Kumar; Regnet, Fabian; Jörissen, Ludwig

2018-05-28

Stability of cathode catalyst support material is one of the big challenges of polymer electrolyte membrane fuel cells (PEMFC) for long term applications. Traditional carbon black (CB) supports are not stable enough to prevent oxidation to CO₂ under fuel cell operating conditions. The feasibility of a graphitized carbon (GC) as a cathode catalyst support for low temperature PEMFC is investigated herein. GC and CB supported Pt electrocatalysts were prepared via an already developed polyol process. The physical characterization of the prepared catalysts was performed using transmission electron microscope (TEM), X-ray Powder Diffraction (XRD) and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis, and their electrochemical characterizations were conducted via cyclic voltammetry(CV), rotating disk electrode (RDE) and potential cycling, and eventually, the catalysts were processed using membrane electrode assemblies (MEA) for single cell performance tests. Electrochemical impedance spectroscopy (EIS) and scanning electrochemical microscopy (SEM) have been used as MEA diagonostic tools. GC showed superior stability over CB in acid electrolyte under potential conditions. Single cell MEA performance of the GC-supported catalyst is comparable with the CB-supported catalyst. A correlation of MEA performance of the supported catalysts of different Brunauer⁻Emmett⁻Teller (BET) surface areas with the ionomer content was also established. GC was identified as a promising candidate for catalyst support in terms of both of the stability and the performance of fuel cell.

Related Studies in Long Term Lithium Battery Stability

NASA Technical Reports Server (NTRS)

Horning, R. J.; Chua, D. L.

1984-01-01

The continuing growth of the use of lithium electrochemical systems in a wide variety of both military and industrial applications is primarily a result of the significant benefits associated with the technology such as high energy density, wide temperature operation and long term stability. The stability or long term storage capability of a battery is a function of several factors, each important to the overall storage life and, therefore, each potentially a problem area if not addressed during the design, development and evaluation phases of the product cycle. Design (e.g., reserve vs active), inherent material thermal stability, material compatibility and self-discharge characteristics are examples of factors key to the storability of a power source.

Platelet-derived Growth Factor-mediated Induction of the Synaptic Plasticity Gene Arc/Arg3.1*

PubMed Central

Peng, Fuwang; Yao, Honghong; Bai, Xuetao; Zhu, Xuhui; Reiner, Benjamin C.; Beazely, Michael; Funa, Keiko; Xiong, Huangui; Buch, Shilpa

2010-01-01

Platelet-derived growth factor (PDGF) is a pleiotropic protein with critical roles in both developmental as well as pathogenic processes. In the central nervous system specifically, PDGF is critical for neuronal proliferation and differentiation and has also been implicated as a neuroprotective agent. Whether PDGF also plays a role in synaptic plasticity, however, remains poorly understood. In the present study we demonstrated that in the rat hippocampal neurons PDGF regulated the expression of Arc/Arg3.1 gene that has been implicated in both synapse plasticity and long term potentiation. Relevance of these findings was further confirmed in vivo by injecting mice with intracerebral inoculations of PDGF, which resulted in a rapid induction of Arc in the hippocampus of the injected mice. PDGF induced long term potentiation in rat hippocampal slices, which was abolished by PDGF receptor-tyrosine kinase inhibitor STI-571. We also present evidence that PDGF-mediated induction of Arc/Arg3.1 involved activation of the MAPK/ERK (MEK) pathway. Additionally, induction of Arc/Arg3.1 also involved the upstream release of intracellular calcium stores, an effect that could be blocked by thapsigargin but not by EGTA. Pharmacological approach using inhibitors specific for either MAPK/ERK phosphorylation or calcium release demonstrated that the two pathways converged downstream at a common point involving activation of the immediate early gene Egr-1. Chromatin immunoprecipitation assays demonstrated the binding of Egr-1, but not Egr-3, to the Arc promoter. These findings for the first time, thus, suggest an additional role of PDGF, that of induction of Arc. PMID:20452974

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

Soil quality assessment in long-term direct seed

USDA-ARS?s Scientific Manuscript database

Producers in the Pacific Northwest are adopting direct seed farming to reduce soil erosion, improve soil quality and increase water infiltration. Some direct seed producers are concerned with reaching the yield and profit potential expected with long-term direct seed, and this may be due to soil st...

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

PubMed Central

Guimarães Marques, Marcia J.; Reyes-Garcia, Selvin Z.; Marques-Carneiro, José E.; Lopes-Silva, Leonardo B.; Andersen, Monica L.; Cavalheiro, Esper A.; Scorza, Fulvio A.; Scorza, Carla A.

2018-01-01

Proechimys are small terrestrial rodents from Amazon rainforest. Each animal species is adapted to a specific environment in which the animal evolved therefore without comparative approaches unique characteristics of distinct species cannot be fully recognized. Laboratory rodents are exceedingly inbred strains dissociated from their native habitats and their fundamental ecological aspects are abstracted. Thus, the employment of exotic non-model species can be informative and complement conventional animal models. With the aim of promoting comparative studies between the exotic wildlife populations in the laboratory and traditional rodent model, we surveyed a type of synaptic plasticity intimately related to memory encoding in animals. Using theta-burst paradigm, in vitro long-term potentiation (LTP) in the CA1 subfield of hippocampal slices was assessed in the Amazon rodents Proechimys and Wistar rats. Memory, learning and anxiety were investigated through the plus-maze discriminative avoidance task (PM-DAT) and object recognition test. In PM-DAT, both animal species were submitted to two test sessions (3-h and 24-h) after the conditioning training. Proechimys exhibited higher anxiety-like behavior in the training session but during test sessions both species exhibited similar patterns of anxiety-related behavior. After 3-h of the training, Proechimys and Wistar spent significantly less time in the aversive enclosed arm than in the non-aversive arm. But, at 24-h after training, Wistar rats remained less time in the aversive closed arm in comparison with the non-aversive one, while Proechimys rodents spent the same amount of time in both enclosed arms. In the object recognition test, both species were evaluated at 24-h after the acquisition session and similar findings than those of the PM-DAT (24-h) were obtained, suggesting that long-term memory duration did not persist for 24-h in the Amazon rodent. Field excitatory post-synaptic potentials recordings revealed

Of trophies and pillars: exploring the terror management functions of short-term and long-term relationship partners.

PubMed

Kosloff, Spee; Greenberg, Jeff; Sullivan, Daniel; Weise, David

2010-08-01

Prior terror management research shows that mortality salience (MS) motivates both self-esteem striving and worldview bolstering. The present research examined these processes in the context of dating preferences. It was hypothesized that in short-term romantic contexts, MS-induced self-esteem striving motivates interest in dating a physically attractive other, whereas in long-term romantic contexts, MS-induced motives for worldview validation heighten interest in dating a same-religion other. Study 1 showed that in a short-term dating context, MS increased preference for an attractive but religiously dissimilar person, whereas in a long-term dating context, MS increased preference for a religiously similar, less attractive person. Study 2 clarified that MS motivates preference for attractive short-term partners for their self-enhancing properties rather than their potential sexual availability. Study 3 supported the theorized processes, showing that under MS, self-esteem-relevant constructs became spontaneously accessible in short-term dating contexts, whereas worldview-relevant constructs became spontaneously accessible in long-term dating contexts.

Do Firms Underinvest in Long-Term Research? Evidence from Cancer Clinical Trials.

PubMed

Budish, Eric; Roin, Benjamin N; Williams, Heidi

2015-07-01

We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials--and hence, project durations--are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinical-trial endpoints, targeted R&D subsidies, and patent design.

Do firms underinvest in long-term research? Evidence from cancer clinical trials.

PubMed

Budish, Eric; Roin, Benjamin N; Williams, Heidi

2015-07-01

We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials - and hence, project durations - are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinicaltrial endpoints, targeted R&D subsidies, and patent design.

Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

PubMed

Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

2015-07-01

β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term care financing: lessons from France.

PubMed

Doty, Pamela; Nadash, Pamela; Racco, Nathalie

2015-06-01

POLICY POINTS: France's model of third-party coverage for long-term services and supports (LTSS) combines a steeply income-adjusted universal public program for people 60 or older with voluntary supplemental private insurance. French and US policies differ: the former pay cash; premiums are lower; and take-up rates are higher, in part because employer sponsorship, with and without subsidization, is more common-but also because coverage targets higher levels of need and pays a smaller proportion of costs. Such inexpensive, bare-bones private coverage, especially if marketed as a supplement to a limited public benefit, would be more affordable to those Americans currently most at risk of "spending down" to Medicaid. An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States' long-term care financing reform efforts. We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income

Factors important in the purchase of partnership long-term care insurance.

PubMed

McCall, N; Mangle, S; Bauer, E; Knickman, J

1998-06-01

To understand the factors important in the purchase of long-term care insurance through the Robert Wood Johnson Foundation Partnership for Long-Term Care. Information on the Partnership programs, telephone surveys, data on Partnership purchasers, and random sample frames. Logistic regression analysis is used to examine characteristics associated with the purchase of a Partnership insurance policy. Independent variables are health status, demographic and financial characteristics, knowledge, and attitudes. A telephone survey of Partnership purchasers and a random sample of the population in each Partnership state were conducted. Survey questions included health status, opinions about long-term care and long-term care insurance, financial planning, demographic characteristics, and income and assets. Important in the purchase of a Partnership policy were variables associated with education and knowledge about long-term care. Other important factors include attitudes and health status. Partnership purchase is associated with higher income and asset levels up to a point, with the effect plateauing and decreasing at the highest income and asset levels. Improved education and knowledge are important in increasing long-term care insurance purchase. Attitudes about having a caregiver, and about the government's role in paying for long-term care as well as the potential purchaser's willingness to consider nursing home care affect policy purchase. Also associated with Partnership policy purchase are better health and middle income and asset levels.

Management training in long-term care.

PubMed

Evashwick, Connie

2002-01-01

The education of health care administrators faces its most dramatic change since the inception of the field. Recent discussions at the national level call for major overhaul of curricula and teaching modalities, including moving education to position students for evidence-based practice. This paper presents recommendations for incorporating training about chronic and long-term care into health care management curricula. It asserts that all health care management students should have a basic knowledge of the fundamental policy, operating, and financing principles of long-term care. The majority of people using the health care delivery system today, and increasingly in the future, suffer from chronic conditions. Long-term care services, although less expansive in structure, far outnumber acute care services and health plans. They will grow in the future to meet the portending demand. To maximize job opportunities and to optimize performance in any job, health care administrators need to know about the long-term care delivery system. This paper delineates critical topics pertaining to long-term care, organized according to 11 fundamental management areas in which the field is developing core competencies. The contents were derived from a year-long process of asking stakeholders in the various facets of long-term care what topics they thought were essential for administrators to know. The topics delineated in this document represent the consensus about essential knowledge that all health care administrators should have about long-term care, whether specializing in long-term care or following a more general management career. The education of health care administrators faces its most dramatic change since the inception ofthe field. Recent discussions at the national level call for major overhaul of curricula and teaching modalities, including moving education to position students to perform according to evidence-based practice. It is thus timely to consider content, as

Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

PubMed Central

Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

2012-01-01

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI. PMID:16575026

Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training.

PubMed

Shields, Richard K; Dudley-Javoroski, Shauna; Littmann, Andrew E

2006-08-01

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI.

Long-term lead elimination from plasma and whole blood after poisoning.

PubMed

Rentschler, Gerda; Broberg, K; Lundh, T; Skerfving, S

2012-04-01

Blood lead (B-Pb), one of the most used toxicological biomarker all kind, has serious limitations. Thus, the objective is to evaluate whether plasma lead (P-Pb) is more adequate. A long-term follow-up study of five cases of lead poisoning. P-Pb was analysed by inductively coupled plasma mass spectrometry. Kinetics after end of exposure was modelled. P-Pb at severe poisoning was about 20 μg/L; haematological effects at about 5 μg/L. Biological half-time of P-Pb was about 1 month; B-Pb decay was much slower. P-Pb is a valuable biomarker of exposure to and risk, particularly at high exposure.

Placenta previa and long-term morbidity of the term offspring.

PubMed

Walfisch, Asnat; Beharier, Ofer; Shoham-Vardi, Ilana; Sergienko, Ruslan; Landau, Daniella; Sheiner, Eyal

2016-08-01

The long-term impact of placenta previa on term infants is unknown. We aimed to investigate whether abnormal placentation increases the risk for long-term morbidity of the term offspring. A population-based cohort study compared the incidence of long-term hospitalizations up to the age of 18 due to cardiovascular, endocrine, neurological, hematological, respiratory and urinary morbidity of children born at term in pregnancies diagnosed with placenta previa and those without. Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies, and fetal congenital malformations were excluded. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence over time. A multivariable generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters. During the study period 233,123 term deliveries met the inclusion criteria; 0.2% (n=502) of the children were born to mothers with placenta previa. During the follow-up period, children born to mothers with placenta previa did not have an increased risk for long-term cardiovascular, endocrine, hematological, neurological, respiratory, and urinary morbidity. Term offsprings of mothers diagnosed with placenta previa do not appear to be at an increased risk for long-term morbidity up to the age of 18. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-term exposure to acidification disrupts reproduction in a marine invertebrate

PubMed Central

Hattich, Giannina S. I.; Heinrichs, Mara E.; Pansch, Andreas; Zagrodzka, Zuzanna; Havenhand, Jonathan N.

2018-01-01

Climate change research is advancing to more complex and more comprehensive studies that include long-term experiments, multiple life-history stages, multi-population, and multi-trait approaches. We used a population of the barnacle Balanus improvisus known to be sensitive to short-term acidification to determine its potential for long-term acclimation to acidification. We reared laboratory-bred individuals (as singles or pairs), and field-collected assemblages of barnacles, at pH 8.1 and 7.5 (≈ 400 and 1600 μatm pCO2 respectively) for up to 16 months. Acidification caused strong mortality and reduced growth rates. Acidification suppressed respiration rates and induced a higher feeding activity of barnacles after 6 months, but this suppression of respiration rate was absent after 15 months. Laboratory-bred barnacles developed mature gonads only when they were held in pairs, but nonetheless failed to produce fertilized embryos. Field-collected barnacles reared in the laboratory for 8 months at the same pH’s developed mature gonads, but only those in pH 8.1 produced viable embryos and larvae. Because survivors of long-term acidification were not capable of reproducing, this demonstrates that B. improvisus can only partially acclimate to long-term acidification. This represents a clear and significant bottleneck in the ontogeny of this barnacle population that may limit its potential to persist in a future ocean. PMID:29408893

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

PubMed

Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G

2016-05-01

We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All

Short-term versus long-term rainfall time series in the assessment of potable water savings by using rainwater in houses.

PubMed

Ghisi, Enedir; Cardoso, Karla Albino; Rupp, Ricardo Forgiarini

2012-06-15

The main objective of this article is to assess the possibility of using short-term instead of long-term rainfall time series to evaluate the potential for potable water savings by using rainwater in houses. The analysis was performed considering rainfall data from 1960 to 1995 for the city of Santa Bárbara do Oeste, located in the state of São Paulo, southeastern Brazil. The influence of the rainfall time series, roof area, potable water demand and percentage rainwater demand on the potential for potable water savings was evaluated. The potential for potable water savings was estimated using computer simulations considering a set of long-term rainfall time series and different sets of short-term rainfall time series. The ideal rainwater tank capacity was also assessed for some cases. It was observed that the higher the percentage rainwater demand and the shorter the rainfall time series, the larger the difference between the potential for potable water savings and the greater the variation in the ideal rainwater tank size. The sets of short-term rainfall time series considered adequate for different scenarios ranged from 1 to 13 years depending on the roof area, percentage rainwater demand and potable water demand. The main finding of the research is that sets of short-term rainfall time series can be used to assess the potential for potable water savings by using rainwater, as the results obtained are similar to those obtained from the long-term rainfall time series. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long-term data archiving

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 recreatemore » 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

Phenomenological and molecular-level Petri net modeling and simulation of long-term potentiation.

PubMed

Hardy, S; Robillard, P N

2005-10-01

Petri net-based modeling methods have been used in many research projects to represent biological systems. Among these, the hybrid functional Petri net (HFPN) was developed especially for biological modeling in order to provide biologists with a more intuitive Petri net-based method. In the literature, HFPNs are used to represent kinetic models at the molecular level. We present two models of long-term potentiation previously represented by differential equations which we have transformed into HFPN models: a phenomenological synapse model and a molecular-level model of the CaMKII regulation pathway. Through simulation, we obtained results similar to those of previous studies using these models. Our results open the way to a new type of modeling for systems biology where HFPNs are used to combine different levels of abstraction within one model. This approach can be useful in fully modeling a system at the molecular level when kinetic data is missing or when a full study of a system at the molecular level it is not within the scope of the research.

Long-Term Control Medications for Lung Diseases

MedlinePlus

... Asthma Medications Long-Term Control Medications Long-Term Control Medications Make an Appointment Ask a Question Refer Patient Long-term control medications are taken daily to control and prevent ...

A Power-Efficient Bio-Potential Acquisition Device with DS-MDE Sensors for Long-Term Healthcare Monitoring Applications

PubMed Central

Chang, Chia-Lin; Chang, Chih-Wei; Huang, Hong-Yi; Hsu, Chen-Ming; Huang, Chia-Hsuan; Chiou, Jin-Chern; Luo, Ching-Hsing

2010-01-01

This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery. PMID:22399907

A power-efficient bio-potential acquisition device with DS-MDE sensors for long-term healthcare monitoring applications.

PubMed

Chang, Chia-Lin; Chang, Chih-Wei; Huang, Hong-Yi; Hsu, Chen-Ming; Huang, Chia-Hsuan; Chiou, Jin-Chern; Luo, Ching-Hsing

2010-01-01

This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery.

Reforming Long-Term Care Funding in Alberta.

PubMed

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

Protein kinase M ζ and the maintenance of long-term memory.

PubMed

Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

2016-10-01

Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Individual decision making in the non-purchase of long-term care insurance.

PubMed

Curry, Leslie A; Robison, Julie; Shugrue, Noreen; Keenan, Patricia; Kapp, Marshall B

2009-08-01

Although prior research suggests that economic, behavioral, and psychosocial factors influence decisions not to purchase long-term care insurance, few studies have examined the interplay among these factors in depth and from the consumer's point of view. This study was intended to further illuminate these considerations, generate hypotheses about non-purchasing decisions, and inform the design of policies that are responsive to concerns and preferences of potential purchasers. Qualitative study using 32 in-depth interviews and 6 focus groups, following a grounded theory approach. Five themes characterize decisions not to purchase long-term care insurance: (a) the determination that a policy is "too costly" reflects highly individualized and complex trade-offs not solely economic in nature, (b) non-purchasers are skeptical about the viability and integrity of private insurance companies and seek an unbiased source of information, (c) family dynamics play an important role in insurance decisions, (d) contemplating personal risk for long-term care triggers psychological responses that have implications for decision making, and (e) non-purchasers feel inadequately informed and overwhelmed by the process of deciding whether to purchase long-term care insurance. States are seeking to offset escalating Medicaid long-term care expenditures through a variety of policy mechanisms, including stimulating individual purchase of long-term care insurance. Findings suggest that economic incentives such as lowering premiums will be necessary but not sufficient to attract appropriate candidates. Attention to behavioral and psychosocial factors is essential to designing incentives that are responsive to concerns and preferences of potential purchasers.

Viability of long-term gene therapy in the cochlea.

PubMed

Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Richardson, Rachael T

2014-04-22

Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss.

Do firms underinvest in long-term research? Evidence from cancer clinical trials

PubMed Central

Budish, Eric; Roin, Benjamin N.

2015-01-01

We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials – and hence, project durations – are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinicaltrial endpoints, targeted R&D subsidies, and patent design. PMID:26345455

[Isolation,culture and identification of adipose-derived stem cells from SD rat adipose tissues subjected to long-term cryopreservation].

PubMed

Liu, Qin; Wang, Liping; Chen, Fang; Zhang, Yi

2017-02-01

To study the feasibility of isolation and culture of adipose-derived stem cells( ADSCs) from SD rat adipose tissues subjected to long-term cryopreservation. We took inguinal fat pads from healthy SD rats. Adipose tissues were stored with 100 m L / L dimethyl sulfoxide( DMSO) combined with 900 m L / L fetal bovine serum( FBS) in liquid nitrogen. Three months later,the adipose tissues were resuscitated for the isolation and culture of ADSCs. The growth status and morphology were observed. The growth curve and cell surface markers CD29,CD45,CD90 of the 3rd passage cells were analyzed respectively by CCK-8 assay and immunocytochemistry. The 3rd passage cells were induced towards adipogenic lineages and osteogenic lineages by different inducers,and the resulting cells were examined separately by oil red O staining and alizarin red staining. The ADSCs obtained from SD rat adipose tissues subjected to long-term cryopreservation showed a spindle-shape appearance and had a good proliferation ability. The cell growth curve was typical "S " curve.Immunocytochemistry showed that the 3rd passage cells were positive for CD29 and CD90,while negative for CD45. The cells were positive for oil red O staining after adipogenic induction,and also positive for alizarin red staining after osteogenic induction. The ADSCs can be isolated from SD rat adipose tissues subjected to long-term cryopreservation.

Going Solar Yields Long-Term Economical, Educational Benefits

ERIC Educational Resources Information Center

von Moos, Brian

2009-01-01

Going solar is not an easy decision, but a long-term investment with a potentially substantial up-front cost. While some schools have enough capital in reserve, can raise bond money, or can solicit sufficient donations, many schools rely on creative financial programs to make a solar energy system economically feasible. Thinking about going solar…

Long-Term Monitoring Research Needs: A DOE Perspective

NASA Astrophysics Data System (ADS)

Moore, B.; Davis, C. B.

2002-05-01

critically on the validity and uncertainty in models used to predict contaminant fate and transport. This is an area of active research at the present time. We survey joint research initiatives in this area involving DOE along with USGS, U.S. EPA, U.S. NRC, and U.S. DOA and non-Federal collaborators, and explore their potential for furthering DOE long-term monitoring needs and objectives.

Impact of induction treatment before autologous stem cell transplantation on long-term outcome in patients with newly diagnosed multiple myeloma.

PubMed

Gassiot, Susanna; Motlló, Cristina; Llombart, Inuska; Morgades, Mireia; González, Yolanda; Garcia-Caro, Montse; Ribera, Josep-Maria; Oriol, Albert

2017-06-01

Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. Patients with consecutive MM <70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with NAs upfront (NA cohort, 65 patients). Patients in the NA cohort demonstrated a superior median PFS (2.8 years vs 1.6 years, P=.03) and also a median PFS from diagnosis to second progression (5.2 years vs 2.7 years, P=.003). After a median follow-up of 7 years, clear differences in OS were observed (7.97 years in NA cohort compared to 3.35 years in CC cohort, P<.001). New agent-based first-line induction treatments provide benefits in both PFS and beyond that point, contributing to a significant improvement in OS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term impact of precision agriculture on a farmer’s field

USDA-ARS?s Scientific Manuscript database

Targeting management practices and inputs with precision agriculture has high potential to meet some of the grand challenges of sustainability in the coming century. Although potential is high, few studies have documented long-term effects of precision agriculture on crop production and environmenta...

The Long-Term Budget Outlook

DTIC Science & Technology

2005-12-01

Revenues Under CBO’s Long-Term Budget Scenarios 56A-8. Real Gross Domestic Product Under CBO’s Long-Term Budget Scenarios 57A-9. Total Surplus or...scenarios suggest that total federal spending for Medicare and Medicaid in 2050 could range anywhere from 7 percent of gross domestic product (GDP)—a...see the Congressional Budget Office’s glossary of budgetary and economic terms, available at www.cbo.gov. 2. The future path of productivity growth

The long-term psychiatric and medical prognosis of perinatal mental illness.

PubMed

Meltzer-Brody, Samantha; Stuebe, Alison

2014-01-01

The perinatal period provides an important window into a woman's long-term health. Perinatal mental illness is a common condition conferring potential serious long-term psychiatric and medical consequences for the mother and family. It is known that childbirth acts as a powerful trigger for depressive episodes in some women, and that women with histories of a mood disorder are particularly vulnerable. Some evidence links perinatal mental illness with obstetrical complications and reduced lactation initiation and duration. Therefore, perinatal mental illness may be a marker for long-term risk, and may contribute directly to subsequent cardiometabolic disease through both neuroendocrine mechanisms and the effects of mental illness on health behaviours. In clinical practice, these associations underscore the importance of screening and treating women with perinatal mental illness to ensure best possible long-term outcomes. Early screening and treatment may both mitigate the primary disease process and reduce the risk of comorbid medical conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats.

PubMed

Dieni, Cristina V; Ferraresi, Aldo; Sullivan, Jacqueline A; Grassi, Sivarosa; Pettorossi, Vito E; Panichi, Roberto

2018-03-01

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

Long-term bed degradation in Maryland streams (phase 2) : Blue Ridge and western Piedmont provinces [research summary].

DOT National Transportation Integrated Search

2012-03-01

Problem: : Estimation of potential long-term down-cutting of the stream bed is necessary for evaluation and design of bridges for scour and culverts for fish passage. Existing guidelines for assessing this potential long-term bed degradation (LTBD) i...

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

Effects of Inductively Coupled Plasma Hydrogen on Long-Wavelength Infrared HgCdTe Photodiodes

NASA Astrophysics Data System (ADS)

Boieriu, P.; Buurma, C.; Bommena, R.; Blissett, C.; Grein, C.; Sivananthan, S.

2013-12-01

Bulk passivation of semiconductors with hydrogen continues to be investigated for its potential to improve device performance. In this work, hydrogen-only inductively coupled plasma (ICP) was used to incorporate hydrogen into long-wavelength infrared HgCdTe photodiodes grown by molecular-beam epitaxy. Fully fabricated devices exposed to ICP showed statistically significant increases in zero-bias impedance values, improved uniformity, and decreased dark currents. HgCdTe photodiodes on Si substrates passivated with amorphous ZnS exhibited reductions in shunt currents, whereas devices on CdZnTe substrates passivated with polycrystalline CdTe exhibited reduced surface leakage, suggesting that hydrogen passivates defects in bulk HgCdTe and in CdTe.

Sauroxine reduces memory retention in rats and impairs hippocampal long-term potentiation generation.

PubMed

Vallejo, Mariana; Carlini, Valeria; Gabach, Laura; Ortega, M G; L Cabrera, José; de Barioglio, Susana Rubiales; Pérez, Mariela; Agnese, Alicia M

2017-07-01

In the present paper it was investigated the role of sauroxine, an alkaloid of Phlegmariurus saururus, as a modulator of some types of learning and memory, considering the potential nootropic properties previously reported for the alkaloid extract and the main alkaloid sauroine. Sauroxine was isolated by means of an alkaline extraction, purified by several chromatographic techniques, and assayed in electrophysiological experiments on rat hippocampus slices, tending towards the elicitation of the long-term potentiation (LTP) phenomena. It was also studied the effects of intrahippocampal administration of sauroxine on memory retention in vivo using a Step-down test. Being the bio distribution of a drug an important parameter to be considered, the concentration of sauroxine in rat brain was determined by GLC-MS. Sauroxine blocked LTP generation at both doses used, 3.65 and 3.610 -2 μM. In the behavioral test, the animals injected with this alkaloid (3.6510 -3 nmol) exhibited a significant decrease on memory retention compared with control animals. It was also showed that sauroxine reached the brain (3.435μg/g tissue), after an intraperitoneal injection, displaying its ability to cross the blood-brain barrier. Thus, sauroxine demonstrated to exert an inhibition on these mnemonic phenomena. The effect here established for 1 is defeated by other constituents according to the excellent results obtained for P. saururus alkaloid extract as well as for the isolated alkaloid sauroine. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Long-term CO2 production following permafrost thawing

Treesearch

B. Elberling; A. Michelsen; C. Schadel; E.A.G. Schuur; H.H. Christiansen; L. Berg; M.P. Tamstorf; C. Sigsgaard

2013-01-01

Thawing permafrost represents a poorly understood feedback mechanism of climate change in the Arctic, but with a potential impact owing to stored carbon being mobilized1–5. We have quantified the long-term loss of carbon (C) from thawing permafrost in Northeast Greenland from 1996 to 2008 by combining repeated sediment sampling to assess changes...

Short-term Action Intentions Overrule Long-Term Semantic Knowledge

ERIC Educational Resources Information Center

van Elk, M.; van Schie, H.T.; Bekkering, H.

2009-01-01

In the present study, we investigated whether the preparation of an unusual action with an object (e.g. bringing a cup towards the eye) could selectively overrule long-term semantic representations. In the first experiment it was found that unusual action intentions activated short-term semantic goal representations, rather than long-term…

Globalization, women's migration, and the long-term-care workforce.

PubMed

Browne, Colette V; Braun, Kathryn L

2008-02-01

With the aging of the world's population comes the rising need for qualified direct long-term-care (DLTC) workers (i.e., those who provide personal care to frail and disabled older adults). Developed nations are increasingly turning to immigrant women to fill these needs. In this article, we examine the impact of three global trends-population aging, globalization, and women's migration-on the supply and demand for DLTC workers in the United States. Following an overview of these trends, we identify three areas with embedded social justice issues that are shaping the DLTC workforce in the United States, with a specific focus on immigrant workers in these settings. These include world poverty and economic inequalities, the feminization and colorization of labor (especially in long-term care), and empowerment and women's rights. We conclude with a discussion of the contradictory effects that both population aging and globalization have on immigrant women, source countries, and the long-term-care workforce in the United States. We raise a number of policy, practice, and research implications and questions. For policy makers and long-term-care administrators in receiver nations such as the United States, the meeting of DLTC worker needs with immigrants may result in greater access to needed employees but also in the continued devaluation of eldercare as a profession. Source (supply) nations must balance the real and potential economic benefits of remittances from women who migrate for labor with the negative consequences of disrupting family care traditions and draining the long-term-care workforce of those countries.

Archiving Primary Data: Solutions for Long-Term Studies.

PubMed

Mills, James A; Teplitsky, Céline; Arroyo, Beatriz; Charmantier, Anne; Becker, Peter H; Birkhead, Tim R; Bize, Pierre; Blumstein, Daniel T; Bonenfant, Christophe; Boutin, Stan; Bushuev, Andrey; Cam, Emmanuelle; Cockburn, Andrew; Côté, Steeve D; Coulson, John C; Daunt, Francis; Dingemanse, Niels J; Doligez, Blandine; Drummond, Hugh; Espie, Richard H M; Festa-Bianchet, Marco; Frentiu, Francesca; Fitzpatrick, John W; Furness, Robert W; Garant, Dany; Gauthier, Gilles; Grant, Peter R; Griesser, Michael; Gustafsson, Lars; Hansson, Bengt; Harris, Michael P; Jiguet, Frédéric; Kjellander, Petter; Korpimäki, Erkki; Krebs, Charles J; Lens, Luc; Linnell, John D C; Low, Matthew; McAdam, Andrew; Margalida, Antoni; Merilä, Juha; Møller, Anders P; Nakagawa, Shinichi; Nilsson, Jan-Åke; Nisbet, Ian C T; van Noordwijk, Arie J; Oro, Daniel; Pärt, Tomas; Pelletier, Fanie; Potti, Jaime; Pujol, Benoit; Réale, Denis; Rockwell, Robert F; Ropert-Coudert, Yan; Roulin, Alexandre; Sedinger, James S; Swenson, Jon E; Thébaud, Christophe; Visser, Marcel E; Wanless, Sarah; Westneat, David F; Wilson, Alastair J; Zedrosser, Andreas

2015-10-01

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Noncontact ECG system for unobtrusive long-term monitoring.

PubMed

McDonald, Neil J; Anumula, Harini A; Duff, Eric; Soussou, Walid

2012-01-01

This paper describes measurements made using an ECG system with QUASAR's capacitive bioelectrodes integrated into a pad system that is placed over a chair. QUASAR's capacitive bioelectrode has the property of measuring bioelectric potentials at a small separation from the body. This enables the measurement of ECG signals through fabric, without the removal of clothing or preparation of skin. The ECG was measured through the subject's clothing while the subject sat in the chair without any supporting action from the subject. The ECG pad system is an example of a high compliance system that places minimal requirements upon the subject and, consequently, can be used to generate a long-term record from ECG segments collected on a daily basis, providing valuable information on long-term trends in cardiac health.

Multi-configuration electromagnetic induction measurements at long term agricultural test sites in Germany with different fertilizer and irrigation managements

NASA Astrophysics Data System (ADS)

Kaufmann, Manuela Sarah; von Hebel, Christian; Brogi, Cosimo; Baumecker, Michael; Döring, Thomas; Amelung, Wulf; Vereecken, Harry; van der Kruk, Jan

2017-04-01

Electromagnetic induction (EMI) data are often being used to investigate large scale soil properties including clay content, soil water content, and salinity changes for a wide range of applications. For agricultural sites, different management practices such as organic/mineral fertilization, tillage, and/or irrigation are important when interpreting the measured apparent electrical conductivity (ECa). Here, we present EMI data recorded at two long term field experiment (LTFE) agricultural test sites in Thyrow near Berlin (Germany), where different long term fertilizer and irrigation management practices were applied. We used two fixed-boom multi-coil EMI instruments that simultaneously measure over nine different depths of investigation (DOI), recording information ranging between the very shallow (0-0.25 m) ploughing zone including the organic matter and the surface soil (A-Horizon) down to the relatively deep (0-2.7 m) subsoil (B-Horizon) or even substratum (C-Horizon). At both test sites, the prevailing sandy to silty sand in the A- and B-Horizon is underlain by a glacial till C-Horizon resulting in generally low ECa values between 0.5 and 5 mS/m. At one test site, a "static nutrient deficiency experiment" is performed since 1937, where organic fertilizer (farm yard manure) and mineral fertilizers (nitrogen-phosphate-potassium (NPK) and liming) are applied at specific grids. Comparing the fertilizer application grid to the measured EMI data, the lowest ECa values coincide to unfertilized grids whereas the ECa values increase with liming, farm yard manure, and NPK. The visually observed correlation between ECa and the liming treatment was possibly due to the increased pH of the soil, because the fertilizer application increases ion contents that increase the soil electrical conductivity. At the second test site, a "Static Irrigation and Fertilizer Experiment" is conducted, where next to the fertilizer treatment (farm yard manure and nitrogen) part of the field

Representational Specificity of Within-Category Phonetic Variation in the Long-Term Mental Lexicon

ERIC Educational Resources Information Center

Ju, Min; Luce, Paul A.

2006-01-01

This study examines the potential encoding in long-term memory of subphonemic, within-category variation in voice onset time (VOT) and the degree to which this encoding of subtle variation is mediated by lexical competition. In 4 long-term repetition-priming experiments, magnitude of priming was examined as a function of variation in VOT in words…

Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms

PubMed Central

Jing, Liang; Duan, Ting-Ting; Tian, Meng; Yuan, Qiang; Tan, Ji-Wei; Zhu, Yong-Yong; Ding, Ze-Yang; Cao, Jun; Yang, Yue-Xiong; Zhang, Xia; Mao, Rong-Rong; Richter-levin, Gal; Zhou, Qi-Xin; Xu, Lin

2015-01-01

The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair. PMID:26449319

Long-term effects of cannabis on oculomotor function in humans.

PubMed

Huestegge, L; Radach, R; Kunert, H J

2009-08-01

Cannabis is known to affect human cognitive and visuomotor skills directly after consumption. Some studies even point to rather long-lasting effects, especially after chronic tetrahydrocannabinol (THC) abuse. However, it is still unknown whether long-term effects on basic visual and oculomotor processing may exist. In the present study, the performance of 20 healthy long-term cannabis users without acute THC intoxication and 20 control subjects were examined in four basic visuomotor paradigms to search for specific long-term impairments. Subjects were asked to perform: 1) reflexive saccades to visual targets (prosaccades), including gap and overlap conditions, 2) voluntary antisaccades, 3) memory-guided saccades and 4) double-step saccades. Spatial and temporal parameters of the saccades were subsequently analysed. THC subjects exhibited a significant increase of latency in the prosaccade and antisaccade tasks, as well as prolonged saccade amplitudes in the antisaccade and memory-guided task, compared with the control subjects. The results point to substantial and specific long-term deficits in basic temporal processing of saccades and impaired visuo-spatial working memory. We suggest that these impairments are a major contributor to degraded performance of chronic users in a vital everyday task like visual search, and they might potentially also affect spatial navigation and reading.

Birds choose long-term partners years before breeding

USGS Publications Warehouse

Teitelbaum, Claire S.; Converse, Sarah J.; Mueller, Thomas

2017-01-01

Pair bonds can provide social benefits to long-term monogamous species alongside their benefits for reproduction. However, little is known about when these bonds form, in particular how long they are present before breeding. Previous studies of pair formation in long-term monogamous birds have been rather data-limited, but for many migratory birds they report pair formation on the wintering grounds. We provide the first systematic investigation of prebreeding association patterns of long-term monogamous pairs by examining entire life histories based on tracking data of migratory whooping cranes, Grus americana. We found that a substantial portion (62%) of breeding pairs started associating at least 12 months before first breeding, with 16 of 58 breeding pairs beginning to associate over 2 years before first breeding. For most pairs, these associations with future breeding partners also became unique and distinguishable from association patterns with nonpartner individuals 12 months before first breeding. In addition, 60% of pair associations began before at least one partner had reached nominal sexual maturity. Most pairs began associating in the late spring upon arrival at the summer grounds, while associations beginning at other times of the year were rare. Patterns in the associations of pairs prior to breeding can point to the potential benefits of prebreeding relationships, for instance providing support in competitive interactions or increasing partner familiarity.

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

PubMed

Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

PubMed Central

Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

2015-01-01

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

Influence of mRNA and protein synthesis inhibitors on the long-term memory acquisition of classically conditioned earthworms.

PubMed

Watanabe, Hikaru; Takaya, Tomohiro; Shimoi, Toshinobu; Ogawa, Hiroto; Kitamura, Yoshiichiro; Oka, Kotaro

2005-03-01

We investigated the process of memory consolidation following classical conditioning of earthworms. Earthworms were conditioned in paired trials by a weak vibration as a conditioned stimulus (CS), and by light as an unconditioned stimulus (US). The occurrence of a shrinking response upon exposure to the CS increased steadily with the number of paired training trials. When the training procedure was changed by increasing the intertrial interval (ITI), it was found that only those worms trained with a 68 s ITI exhibited long-term memory retention for at least 24 h. The influence of mRNA synthesis inhibition by actinomycin-D or of protein synthesis by anisomycin on memory consolidation was also examined. Induction of the long-term memory was blocked when either of these two compounds was injected into the body cavity of the worm within 25 min of conditioning with the 68 s ITI. These results demonstrate that the long-term memory is dependent upon protein synthesis in response to the upregulation of new transcription messengers.

Estimating long-term multivariate progression from short-term data.

PubMed

Donohue, Michael C; Jacqmin-Gadda, Hélène; Le Goff, Mélanie; Thomas, Ronald G; Raman, Rema; Gamst, Anthony C; Beckett, Laurel A; Jack, Clifford R; Weiner, Michael W; Dartigues, Jean-François; Aisen, Paul S

2014-10-01

Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term "Personnes Agées Quid" study. We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm. Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Long-term deconditioning of gas-filled surge arresters

NASA Astrophysics Data System (ADS)

Stanković, Koviljka; Brajović, Dragan; Alimpijević, Mališa; Lončar, Boris

2016-07-01

pressure that is as high as possible (with pd = const), and that the electrode active surface should have a marked microscopic topography. In addition to this, an essential conclusion for GFSA manufacturers is that long-term system deconditioning is caused by impurities and adsorbed gases that appear at electrode during the state of rest. Out of these two causes, the influence of impurities is probably the dominant one, which is proved by considerably reduced long-term deconditioning in the case of noble metal electrodes, not susceptible to corrosion. This has also been confirmed by a less distinct effect of long-term deconditioning in the case of sandblasted electrodes that have a stronger tendency towards gas adsorption and a weaker tendency towards corrosion. However, it has been shown that adding of the third electrode (that is concentric to the main electrode system) on a free floating potential along with usage of sandblasted electrodes and with smaller interelectrode distance significantly reduces the effects of the long-term deconditioning.

Synaptic characteristics with strong analog potentiation, depression, and short-term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure

NASA Astrophysics Data System (ADS)

Kim, Hyung Jun; Park, Daehoon; Yang, Paul; Beom, Keonwon; Kim, Min Ju; Shin, Chansun; Kang, Chi Jung; Yoon, Tae-Sik

2018-06-01

A crossbar array of Pt/CeO2/Pt memristors exhibited the synaptic characteristics such as analog, reversible, and strong resistance change with a ratio of ∼103, corresponding to wide dynamic range of synaptic weight modulation as potentiation and depression with respect to the voltage polarity. In addition, it presented timing-dependent responses such as paired-pulse facilitation and the short-term to long-term memory transition by increasing amplitude, width, and repetition number of voltage pulse and reducing the interval time between pulses. The memory loss with a time was fitted with a stretched exponential relaxation model, revealing the relation of memory stability with the input stimuli strength. The resistance change was further enhanced but its stability got worse as increasing measurement temperature, indicating that the resistance was changed as a result of voltage- and temperature-dependent electrical charging and discharging to alter the energy barrier for charge transport. These detailed synaptic characteristics demonstrated the potential of crossbar array of Pt/CeO2/Pt memristors as artificial synapses in highly connected neuron-synapse network.

Synaptic characteristics with strong analog potentiation, depression, and short-term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure.

PubMed

Kim, Hyung Jun; Park, Daehoon; Yang, Paul; Beom, Keonwon; Kim, Min Ju; Shin, Chansun; Kang, Chi Jung; Yoon, Tae-Sik

2018-06-29

A crossbar array of Pt/CeO 2 /Pt memristors exhibited the synaptic characteristics such as analog, reversible, and strong resistance change with a ratio of ∼10 3 , corresponding to wide dynamic range of synaptic weight modulation as potentiation and depression with respect to the voltage polarity. In addition, it presented timing-dependent responses such as paired-pulse facilitation and the short-term to long-term memory transition by increasing amplitude, width, and repetition number of voltage pulse and reducing the interval time between pulses. The memory loss with a time was fitted with a stretched exponential relaxation model, revealing the relation of memory stability with the input stimuli strength. The resistance change was further enhanced but its stability got worse as increasing measurement temperature, indicating that the resistance was changed as a result of voltage- and temperature-dependent electrical charging and discharging to alter the energy barrier for charge transport. These detailed synaptic characteristics demonstrated the potential of crossbar array of Pt/CeO 2 /Pt memristors as artificial synapses in highly connected neuron-synapse network.

Long-term memory of heterospecific vocalizations by African lions

NASA Astrophysics Data System (ADS)

Grinnell, Jon; van Dyk, Gus; Slotow, Rob

2005-09-01

Animals that use and evaluate long-distance signals have the potential to glean valuable information about others in their environment via eavesdropping. In those areas where they coexist, African lions (Panthera leo) are a significant eavesdropper on spotted hyenas (Crocuta crocuta), often using hyena vocalizations to locate and scavenge from hyena kills. This relationship was used to test African lions' long-term memory of the vocalizations of spotted hyenas via playback experiments. Hyena whoops and a control sound (Canis lupus howls) were played to three populations of lions in South Africa: (1) lions with past experience of spotted hyenas; (2) lions with current experience; and (3) lions with no experience. The results strongly suggest that lions have the cognitive ability to remember the vocalizations of spotted hyenas even after 10 years with no contact of any kind with them. Such long-term memory of heterospecific vocalizations may be widespread in species that gain fitness benefits from eavesdropping on others, but where such species are sympatric and often interact it may pass unrecognized as short-term memory instead.

Experience with long-term glucocorticoid treatment in congenital adrenal hyperplasia: growth pattern compared with genetic height potential.

PubMed

Aycan, Zehra; Ocal, Gonul; Berberoglu, Merih; Cetinkaya, Ergun; Adiyaman, Pelin; Evliyaoglu, Olcay

2006-03-01

Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical CAH had

Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling.

PubMed

Yi, Jee Hyun; Zhang, JiaBao; Ko, Sang Yoon; Kwon, Huiyoung; Jeon, Se Jin; Park, Se Jin; Jung, Jiwook; Kim, Byung C; Lee, Young Choon; Kim, Dong Hyun; Ryu, Jong Hoon

2018-02-09

Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.

Dendritic spine dynamics in synaptogenesis after repeated LTP inductions: Dependence on pre-existing spine density

PubMed Central

Oe, Yuki; Tominaga-Yoshino, Keiko; Hasegawa, Sho; Ogura, Akihiko

2013-01-01

Not only from our daily experience but from learning experiments in animals, we know that the establishment of long-lasting memory requires repeated practice. However, cellular backgrounds underlying this repetition-dependent consolidation of memory remain largely unclear. We reported previously using organotypic slice cultures of rodent hippocampus that the repeated inductions of LTP (long-term potentiation) lead to a slowly developing long-lasting synaptic enhancement accompanied by synaptogenesis distinct from LTP itself, and proposed this phenomenon as a model system suitable for the analysis of the repetition-dependent consolidation of memory. Here we examined the dynamics of individual dendritic spines after repeated LTP-inductions and found the existence of two phases in the spines' stochastic behavior that eventually lead to the increase in spine density. This spine dynamics occurred preferentially in the dendritic segments having low pre-existing spine density. Our results may provide clues for understanding the cellular bases underlying the repetition-dependent consolidation of memory. PMID:23739837

Position-insensitive long range inductive power transfer

NASA Astrophysics Data System (ADS)

Kwan, Christopher H.; Lawson, James; Yates, David C.; Mitcheson, Paul D.

2014-11-01

This paper presents results of an improved inductive wireless power transfer system for reliable long range powering of sensors with milliwatt-level consumption. An ultra-low power flyback impedance emulator operating in open loop is used to present the optimal load to the receiver's resonant tank. Transmitter power modulation is implemented in order to maintain constant receiver power and to prevent damage to the receiver electronics caused by excessive received voltage. Received power is steady up to 3 m at around 30 mW. The receiver electronics and feedback system consumes 3.1 mW and so with a transmitter input power of 163.3 W the receiver becomes power neutral at 4.75 m. Such an IPT system can provide a reliable alternative to energy harvesters for supplying power concurrently to multiple remote sensors.

Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Weili; Xiao, Linlin; Dong, Chen

2014-05-09

Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cellsmore » Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.« less

Impact of long-term wetting on belowground respiration and methanogenesis in Luther Bog, Ontario

NASA Astrophysics Data System (ADS)

Goebel, Marie; Blodau, Christian

2016-04-01

Peatlands play a major role in the global carbon cycle. They store one-third of total world soil carbon, sequester carbon dioxide (CO2) and release CO2 and methane (CH4). Climate and land-use change are predicted to cause either wetter winters and wetter summers or wetter winters and drier summers in the area where northern peatlands are located. Feedback on processes in the peat is poorly understood on the time scale of decades. In this study, we investigated impacts of long-term wetting and long-term fluctuating water table on potential CO2 and CH4 production rates and organic matter quality of the fractions bulk peat, pore water and leachate. Bulk peat potential CO2 production rates of 2.38 to 25.55 μmol g-1 d-1 (aerobic) and 1.53 to 7.33 μmol g-1 d-1 (anaerobic) decreased with depth along with a decrease in organic matter quality. Potential CH4 production rates (0.002 to 2.60 μmol g-1 d-1) increased with anaerobic conditions and a lack of electron acceptors rather than being dependent on the availability of labile organic matter. This pattern was less evident in solute fraction samples where labile compounds in top layers were probably either too labile to be detected or water movement obscured differences between depths. Bulk peat potential anaerobic CO2 and CH4 production increased through long-term wetting. As wetting did not change organic matter quality or aerobic production rates, increased anaerobic production rates likely originate from microorganisms adapted to anaerobic conditions. All indicators of organic matter quality, FTIR ratios, SUVA254, E2:E3, HIX, FI and PARAFAC, provided similar results. Other than expected, wetting did not result in higher organic matter quality in bulk peat and leachate. Drier conditions in summer led to reduced organic matter quality. In pore water, long-term wetter conditions resulted in a higher organic matter quality. Slow-down of decomposition due to anaerobic conditions is unlikely, as this was not the case with

Space Life Sciences Research: The Importance of Long-Term Space Experiments

NASA Technical Reports Server (NTRS)

1993-01-01

This report focuses on the scientific importance of long-term space experiments for the advancement of biological science and the benefit of humankind. It includes a collection of papers that explore the scientific potential provided by the capability to manipulate organisms by removing a force that has been instrumental in the evolution and development of all organisms. Further, it provides the scientific justification for why the long-term space exposure that can be provided by a space station is essential to conduct significant research.

Daily Acclimation Handling Does Not Affect Hippocampal Long-Term Potentiation or Cause Chronic Sleep Deprivation in Mice

PubMed Central

Vecsey, Christopher G.; Wimmer, Mathieu E. J.; Havekes, Robbert; Park, Alan J.; Perron, Isaac J.; Meerlo, Peter; Abel, Ted

2013-01-01

Study Objectives: Gentle handling is commonly used to perform brief sleep deprivation in rodents. It was recently reported that daily acclimation handling, which is often used before behavioral assays, causes alterations in sleep, stress, and levels of N-methyl-D-aspartate receptor subunits prior to the actual period of sleep deprivation. It was therefore suggested that acclimation handling could mediate some of the observed effects of subsequent sleep deprivation. Here, we examine whether acclimation handling, performed as in our sleep deprivation studies, alters sleep/wake behavior, stress, or forms of hippocampal synaptic plasticity that are impaired by sleep deprivation. Design: Adult C57BL/6J mice were either handled daily for 6 days or were left undisturbed in their home cages. On the day after the 6th day of handling, long-term potentiation (LTP) was induced in hippocampal slices with spaced four-train stimulation, which we previously demonstrated to be impaired by brief sleep deprivation. Basal synaptic properties were also assessed. In three other sets of animals, activity monitoring, polysomnography, and stress hormone measurements were performed during the 6 days of handling. Results: Daily gentle handling alone does not alter LTP, rest/activity patterns, or sleep/wake architecture. Handling initially induces a minimal stress response, but by the 6th day, stress hormone levels are unaltered by handling. Conclusion: It is possible to handle mice daily to accustom them to the researcher without causing alterations in sleep, stress, or synaptic plasticity in the hippocampus. Therefore, effects of acclimation handling cannot explain the impairments in signaling mechanisms, synaptic plasticity, and memory that result from brief sleep deprivation. Citation: Vecsey CG; Wimmer MEJ; Havekes R; Park AJ; Perron IJ; Meerlo P; Abel T. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice. SLEEP 2013

Synaptic scaling enables dynamically distinct short- and long-term memory formation.

PubMed

Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Tsodyks, Misha; Wörgötter, Florentin

2013-10-01

Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

Synaptic Scaling Enables Dynamically Distinct Short- and Long-Term Memory Formation

PubMed Central

Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Tsodyks, Misha; Wörgötter, Florentin

2013-01-01

Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling – a slow process usually associated with the maintenance of activity homeostasis – combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes. PMID:24204240

Very long-term sequelae of craniopharyngioma.

PubMed

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn.

PubMed

Jin, Virginia L; Schmer, Marty R; Stewart, Catherine E; Sindelar, Aaron J; Varvel, Gary E; Wienhold, Brian J

2017-07-01

Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emissions, and global warming potential (GWP) in irrigated systems, however, remain relatively unknown. Here, residue and tillage management effects were quantified by measuring soil nitrous oxide (N 2 O) and methane (CH 4 ) fluxes and SOC changes (ΔSOC) at a long-term, irrigated continuous corn (Zea mays L.) system in eastern Nebraska, United States. Management treatments began in 2002, and measured treatments included no or high stover removal (0 or 6.8 Mg DM ha -1  yr -1 , respectively) under no-till (NT) or conventional disk tillage (CT) with full irrigation (n = 4). Soil N 2 O and CH 4 fluxes were measured for five crop-years (2011-2015), and ΔSOC was determined on an equivalent mass basis to ~30 cm soil depth. Both area- and yield-scaled soil N 2 O emissions were greater with stover retention compared to removal and for CT compared to NT, with no interaction between stover and tillage practices. Methane comprised <1% of total emissions, with NT being CH 4 neutral and CT a CH 4 source. Surface SOC decreased with stover removal and with CT after 14 years of management. When ΔSOC, soil GHG emissions, and agronomic energy usage were used to calculate system GWP, all management systems were net GHG sources. Conservation practices (NT, stover retention) each decreased system GWP compared to conventional practices (CT, stover removal), but pairing conservation practices conferred no additional mitigation benefit. Although cropping system, management equipment/timing/history, soil type, location, weather, and the depth to which ΔSOC is measured affect the GWP outcomes of irrigated systems at large, this long-term irrigated study provides valuable empirical evidence of how management decisions can impact soil GHG emissions and surface

Long-term care in international perspective.

PubMed

Doty, P

1988-12-01

The findings of a study of long-term care policies in 18 countries are reported in this article. Initial data were collected by a questionnaire survey under the auspices of the International Social Security Association. These data were supplemented by published documents and government statistics obtained while researching long-term care for the International Social Security Association and, subsequently, for the Organization for Economic Cooperation and Development. The principal focus is a cross-national comparison of institutionalization rates for the elderly. Differences in use rates for medically oriented facilities are less than those for nonmedical residential long-term care facilities. Only a small amount of variation is related to demographic differences, such as older or more female elderly populations in those countries with higher institutionalization rates. Included also is a description of the modes of financing long-term care.

Comparative study of titrated oral misoprostol solution and vaginal dinoprostone for labor induction at term pregnancy.

PubMed

Wang, Xiu; Yang, Aijun; Ma, Qingyong; Li, Xuelan; Qin, Li; He, Tongqiang

2016-09-01

To evaluate effectiveness and safety of titrated oral misoprostol solution (OMS) in comparison with vaginal dinoprostone for cervix ripening and labor induction in term pregnant women. A multicenter randomized controlled trial of women with term singleton pregnancy with indications for labor induction; 481 participants were allocated to receive titrated OMS with different doses by hourly administration according to the procedure or insert vaginal dinoprostone for cervix ripening and labor induction to compare maternal outcomes including indication of labor induction, mode of outcome of delivery, maternal morbidity, and neonatal outcomes between two groups for evaluating the efficacy and safety of titrated oral misoprostol induction. Proportion of delivery within 12 h of titrated oral misoprostol is significantly less than vaginal dinoprostone (p = 0.03), but no difference of total vaginal delivery rate (p = 0.93); the mean time of first treatment to vaginal delivery was longer in OMS group (21.3 ± 14.5 h) compared with the vaginal dinoprostone group (15.7 ± 9.6 h). Although the proportion of cesarean section between the two groups showed no statistically significant difference, OMS group showed significantly lower frequency of uterine hyperstimulation, hypertonus, partus precipitatus and non-reassuring fetal heart rate than dinoprostone group. Neonatal outcomes were similar evaluating from Apgar score and NICU admission. Our study also showed that labor induction of women with cervix Bishop score ≤3 needed increased dosage of misoprostol solution. Titrated OMS is as effective as vaginal dinoprostone in labor induction for term pregnant women, with safer effect for its lower rate of adverse effect for women.

Long-term potentiation protects rat hippocampal slices from the effects of acute hypoxia.

PubMed

Youssef, F F; Addae, J I; McRae, A; Stone, T W

2001-07-13

We have previously shown that long-term potentiation (LTP) decreases the sensitivity of glutamate receptors in the rat hippocampal CA1 region to exogenously applied glutamate agonists. Since the pathophysiology of hypoxia/ischemia involves increased concentration of endogenous glutamate, we tested the hypothesis that LTP could reduce the effects of hypoxia in the hippocampal slice. The effects of LTP on hypoxia were measured by the changes in population spike potentials (PS) or field excitatory post-synaptic potentials (fepsps). Hypoxia was induced by perfusing the slice with (i) artificial CSF which had been pre-gassed with 95%N2/5% CO2; (ii) artificial CSF which had not been pre-gassed with 95% O2/5% CO2; or (iii) an oxygen-glucose deprived (OGD) medium which was similar to (ii) and in which the glucose had been replaced with sucrose. Exposure of a slice to a hypoxic medium for 1.5-3.0 min led to a decrease in the PS or fepsps; the potentials recovered to control levels within 3-5 min. Repeat exposure, 45 min later, of the same slice to the same hypoxic medium for the same duration as the first exposure caused a reduction in the potentials again; there were no significant differences between the degree of reduction caused by the first or second exposure for all three types of hypoxic media (P>0.05; paired t-test). In some of the slices, two episodes of LTP were induced 25 and 35 min after the first hypoxic exposure; this caused inhibition of reduction in potentials caused by the second hypoxic insult which was given at 45 min after the first; the differences in reduction in potentials were highly significant for all the hypoxic media used (P<0.01; paired t-test). The neuroprotective effects of LTP were not prevented by cyclothiazide or inhibitors of NO synthetase compounds that have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to those

Channel gating kinetics and synaptic efficacy: a hypothesis for expression of long-term potentiation.

PubMed Central

Ambros-Ingerson, J; Lynch, G

1993-01-01

A kinetic model of the glutamate DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor/channel complex was used to test whether changes in the rate constants describing channel behavior could account for various features of long-term potentiation (LTP). Starting values for the kinetic parameters were set to satisfy experimental data (e.g., affinity, mean open time, mean burst length, etc.) and physical constraints (i.e., microreversibility). The resultant model exhibited a variety of dynamic properties known to be associated with the receptor. Increasing the rate constants governing opening/closing of the channel produced an unexpected increase in the probability of the channel being open shortly after transmitter binding. This would account for the enhanced response size with LTP. Increases in rate constants produced two other aspects of LTP: (i) an alteration of the waveform of the synaptic response and (ii) an interaction with changes in desensitization kinetics. The results obtained with the model corresponded closely to those found in LTP experiments. Thus, an increase in opening/closing rates for the postsynaptic receptor channel provides a single explanation for diverse characteristics of LTP. Finally, the kinetic manipulation reduced the coefficient of variation of synaptic currents in a model involving 250 receptors. This calls into question the use of variance measures for distinguishing pre- vs. postsynaptic sites of potentiation. PMID:8395058

Long-term athletic development- part 1: a pathway for all youth.

PubMed

Lloyd, Rhodri S; Oliver, Jon L; Faigenbaum, Avery D; Howard, Rick; De Ste Croix, Mark B A; Williams, Craig A; Best, Thomas M; Alvar, Brent A; Micheli, Lyle J; Thomas, D Phillip; Hatfield, Disa L; Cronin, John B; Myer, Gregory D

2015-05-01

The concept of developing talent and athleticism in youth is the goal of many coaches and sports systems. Consequently, an increasing number of sporting organizations have adopted long-term athletic development models in an attempt to provide a structured approach to the training of youth. It is clear that maximizing sporting talent is an important goal of long-term athletic development models. However, ensuring that youth of all ages and abilities are provided with a strategic plan for the development of their health and physical fitness is also important to maximize physical activity participation rates, reduce the risk of sport- and activity-related injury, and to ensure long-term health and well-being. Critical reviews of independent models of long-term athletic development are already present within the literature; however, to the best of our knowledge, a comprehensive examination and review of the most prominent models does not exist. Additionally, considerations of modern day issues that may impact on the success of any long-term athletic development model are lacking, as are proposed solutions to address such issues. Therefore, within this 2-part commentary, Part 1 provides a critical review of existing models of practice for long-term athletic development and introduces a composite youth development model that includes the integration of talent, psychosocial and physical development across maturation. Part 2 identifies limiting factors that may restrict the success of such models and offers potential solutions.

Representativeness of shorter measurement sessions in long-term indoor air monitoring.

PubMed

Maciejewska, M; Szczurek, A

2015-02-01

Indoor air quality (IAQ) considerably influences health, comfort and the overall performance of people who spend most of their lives in confined spaces. For this reason, there is a strong need to develop methods for IAQ assessment. The fundamental issue in the quantitative determination of IAQ is the duration of measurements. Its inadequate choice may result in providing incorrect information and this potentially leads to wrong conclusions. The most complete information may be acquired through long-term monitoring. However it is typically perceived as impractical due to time and cost load. The aim of this study was to determine whether long-term monitoring can be adequately represented by a shorter measurement session. There were considered three measurable quantities: temperature, relative humidity and carbon dioxide concentration. They are commonly recognized as indicatives for IAQ and may be readily monitored. Scaled Kullback-Leibler divergence, also called relative entropy, was applied as a measure of data representativeness. We considered long-term monitoring in a range from 1 to 9 months. Based on our work, the representative data on CO2 concentration may be acquired while performing measurements during 20% of time dedicated to long-term monitoring. In the case of temperature and relative humidity the respective time demand was 50% of long-term monitoring. From our results, in indoor air monitoring strategies, there could be considered shorter measurement sessions, while still collecting data which are representative for long-term monitoring.

A role for N-methyl-D-aspartate receptors in norepinephrine-induced long-lasting potentiation in the dentate gyrus.

PubMed

Stanton, P K; Mody, I; Heinemann, U

1989-01-01

Mechanisms of action of norepinephrine (NE) on dentate gyrus granule cells were studied in rat hippocampal slices using extra- and intracellular recordings and measurements of stimulus and amino acid-induced changes in extracellular Ca2+ and K+ concentration. Bath application of NE (10-50 microM) induced long-lasting potentiation of perforant path evoked potentials, and markedly enhanced high-frequency stimulus-induced Ca2+ influx and K+ efflux, actions blocked by beta-receptor antagonists and mimicked by beta agonists. Enhanced Ca2+ influx was primarily postsynaptic, since presynaptic delta [Ca2+]o in the stratum moleculare synaptic field was not altered by NE. Interestingly, the potentiation of both ionic fluxes and evoked population potentials were antagonized by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). Furthermore, NE selectively enhanced the delta [Ca2+]o delta [K+]o and extracellular slow negative field potentials elicited by iontophoretically applied NMDA, but not those induced by the excitatory amino acid quisqualate. These results suggest that granule cell influx of Ca2+ through NMDA ionophores is enhanced by NE via beta-receptor activation. In intracellular recordings, NE depolarized granule cells (4.8 +/- 1.1 mV), and increased input resistance (RN) by 34 +/- 6.5%. These actions were also blocked by either the beta-antagonist propranolol or specific beta 1-blocker metoprolol. Moreover, the depolarization and RN increase persisted for long periods (93 +/- 12 min) after NE washout. In contrast, while NE, in the presence of APV, still depolarized granule cells and increased RN, APV made these actions quickly reversible upon NE washout (16 +/- 9 min). This suggested that NE induction of long-term, but not short-term, plasticity in the dentate gyrus requires NMDA receptor activation. NE may be enhancing granule cell firing by some combination of blockade on the late Ca2+-activated K+ conductance and depolarization

Competitive short-term and long-term memory processes in spatial habituation.

PubMed

Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

PubMed

Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

2016-04-13

The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal

Long-term Autophagy and Nrf2 Signaling in the Hippocampi of Developing Mice after Carbon Ion Exposure

NASA Astrophysics Data System (ADS)

Ye, Fei; Zhao, Ting; Liu, Xiongxiong; Jin, Xiaodong; Liu, Xinguo; Wang, Tieshan; Li, Qiang

2015-12-01

To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi. Secondary X-ray insult was adopted to amplify potential damages. Long-term behavioral changes were observed in high-LET carbon ion-irradiated mice. There were no differences in the rates of LC3-II induction and p62/SQSTM1 degradation compared to the control group regardless of whether the mice received the secondary X-ray insult. A high nuclear Nrf2 content and low apoptosis level in hippocampal cells subjected to secondary X-rays were observed for the mice exposed to relatively low-LET carbon ions. Therefore, carbon ion exposure in the immature mouse led to an LET-dependent behavioral change after maturation. Although autophagy was intact, the persistently high nuclear Nrf2 content in the hippocampus might account for the unchanged behavioral pattern in mice exposed to the relatively low-LET carbon ions and the subsequent increased radioresistance of the hippocampus.

[Clinical evaluation of propess for induction of term pregnancy].

PubMed

Gai, Ming-ying; Zhang, Jian-ping; Li, Yang; Han, Hong-jing; Yang, Jian-qiu; Wang, Shan-mi; Su, Qi-feng; Wu, Lian-fang

2003-04-01

To explore the efficacy and safety of continuously released prostaglandin E(2) (PGE(2)) suppository-propess used for induction of term pregnancy. A multicenter, prospective, case control clinical study was carried out, propess was used in 100 cases as study group, the suppository without PGE(2) was used in 49 cases as control group. The cervical maturity (by Bishop scoring), the time to labor starting, membrane rupture and delivery, the application of oxytocin, ceserean section rate, fetal and neonatal condition were compared between 2 groups after inserting of the suppository. At the same time, side effects caused by propess were investigated. Bishop score was increased >or= 2 points in 93% cases, >or= 3 points in 87% cases in study group, whereas only 4% cases whose Bishop score increased >or= 2 points in control group. The time to labor starting, membrane rupture, and delivery was shortened obviously in study group than that in control group after inserting suppository. The application of oxytocin was much less in study group, cesarean section rate was reduced in study group (32% vs 61%). There was no significant difference between 2 groups in fetal and neonatal conditions. The overstimulation of uterine contraction and mild gastrointestinal tract reaction occurred in 3 cases and 2 cases respectively in study groups. Propess can be used for induction of term pregnancy effectively and safely.

Separation of Electric Fields Into Potential and Inductive Parts, and Implications for Radial Diffusion

NASA Astrophysics Data System (ADS)

Chan, A. A.; Ilie, R.; Elkington, S. R.; Albert, J.; Huie, W.

2017-12-01

It has been traditional to separate radiation belt radial-diffusion coefficients into two contributions: an "electrostatic" diffusion coefficient, which is assumed to be due to a potential (non-inductive) electric field, and an "electromagnetic" diffusion coefficient , which is assumed to be due to the combined effect of an inductive electric field and the corresponding time-dependent magnetic field. One difficulty in implementing this separation when using magnetospheric fields obtained from measurements, or from MHD simulations, is that only the total electric field is given; the separation of the electric field into potential and inductive parts is not readily available. In this work we separate the electric field using a numerical method based on the Helmholtz decomposition of the total motional electric field calculated by the BATS-R-US MHD code. The inner boundary for the electric potential is based on the Ridley Ionospheric Model solution and we assume floating boundary conditions in the solar wind. Using different idealized solar wind drivers, including a solar wind density that is oscillating at a single frequency or with a broad spectrum of frequencies, we calculate potential and inductive electric fields, electric and magnetic power spectral densities, and corresponding radial diffusion coefficients. Simulations driven by idealized solar wind conditions show a clear separation of the potential and inductive contributions to the power spectral densities and diffusion coefficients. Simulations with more realistic solar wind drivers are underway to better assess the use of electrostatic and electromagnetic diffusion coefficients in understanding ULF wave-particle interactions in Earth's radiation belts.

Business Students' Choice of Short-Term or Long-Term Study Abroad Opportunities

ERIC Educational Resources Information Center

Fitzsimmons, Stacey R.; Flanagan, David J.; Wang, Xiaodan

2013-01-01

Recent years have seen a proliferation of short-term study abroad opportunities. Although they are both supplementing and replacing semester-long study abroad programs, research has focused primarily on semester (long-term) programs. We draw on the theory of planned behavior (TPB) to explore factors that predict why students choose long-term and…

A Dynamic Anesthesia System for Long-Term Imaging in Adult Zebrafish

PubMed Central

Wynd, Brenen M.; Watson, Claire J.; Patil, Karuna; Sanders, George E.

2017-01-01

Abstract Long-term in vivo imaging in adult zebrafish (i.e., 1–24 h) has been limited by the fact that regimens for long-term anesthesia in embryos and larvae are ineffective in adults. Here, we examined the potential for dynamic administration of benzocaine to enable long-term anesthesia in adult zebrafish. We developed a computer-controlled perfusion system comprised of programmable peristaltic pumps that enabled automatic exchange between anesthetic and system water. Continuous administration of benzocaine in adult zebrafish resulted in a mean time to respiratory arrest of 5.0 h and 8-h survival of 14.3%. We measured characteristic sedation and recovery times in response to benzocaine, and used them to devise an intermittent dosing regimen consisting of 14.5 min of benzocaine followed by 5.5 min of system water. Intermittent benzocaine administration in adult zebrafish resulted in a mean time to respiratory arrest of 7.6 h and 8-h survival of 71.4%. Finally, we performed a single 24-h trial and found that intermittent dosing maintained anesthesia in an adult zebrafish over the entire 24-h period. In summary, our studies demonstrate the potential for dynamic administration of benzocaine to enable prolonged anesthesia in adult zebrafish, expanding the potential for imaging in adult physiologies that unfold over 1–24 h. PMID:27409411

A Dynamic Anesthesia System for Long-Term Imaging in Adult Zebrafish.

PubMed

Wynd, Brenen M; Watson, Claire J; Patil, Karuna; Sanders, George E; Kwon, Ronald Y

2017-02-01

Long-term in vivo imaging in adult zebrafish (i.e., 1-24 h) has been limited by the fact that regimens for long-term anesthesia in embryos and larvae are ineffective in adults. Here, we examined the potential for dynamic administration of benzocaine to enable long-term anesthesia in adult zebrafish. We developed a computer-controlled perfusion system comprised of programmable peristaltic pumps that enabled automatic exchange between anesthetic and system water. Continuous administration of benzocaine in adult zebrafish resulted in a mean time to respiratory arrest of 5.0 h and 8-h survival of 14.3%. We measured characteristic sedation and recovery times in response to benzocaine, and used them to devise an intermittent dosing regimen consisting of 14.5 min of benzocaine followed by 5.5 min of system water. Intermittent benzocaine administration in adult zebrafish resulted in a mean time to respiratory arrest of 7.6 h and 8-h survival of 71.4%. Finally, we performed a single 24-h trial and found that intermittent dosing maintained anesthesia in an adult zebrafish over the entire 24-h period. In summary, our studies demonstrate the potential for dynamic administration of benzocaine to enable prolonged anesthesia in adult zebrafish, expanding the potential for imaging in adult physiologies that unfold over 1-24 h.

Immediate and Long-Term Impacts of Child Sexual Abuse.

ERIC Educational Resources Information Center

Briere, John N.; Elliott, Diana M.

1994-01-01

Summarizes what is currently known about the potential, immediate, and long-term impact of child sexual abuse. The various problems and symptoms described in the literature on child sexual abuse are reviewed in a series of broad categories including posttraumatic stress, cognitive distortions, emotional pain, avoidance, an impaired sense of self,…

Long-term forest management and climate effects on streamflow

Treesearch

Shelby G. Laird; C.R. Ford; S.H. Laseter; J.M. Vose

2011-01-01

Long-term watershed studies are a powerful tool for examining interactions among management activities, streamflow, and climatic variability. Understanding these interactions is critical for exploring the potential of forest management to adapt to or mitigate against the effects of climate change. The Coweeta Hydrologic Laboratory, located in North Carolina, USA, is a...

Effects of Joint Attention on Long-Term Memory in 9-Month-Old Infants: An Event-Related Potentials Study

ERIC Educational Resources Information Center

Kopp, Franziska; Lindenberger, Ulman

2011-01-01

Joint attention develops during the first year of life but little is known about its effects on long-term memory. We investigated whether joint attention modulates long-term memory in 9-month-old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high…

Hypomagnesaemia associated with long-term use of proton pump inhibitors

PubMed Central

Toh, James Wei Tatt; Ong, Evonne; Wilson, Robert

2015-01-01

Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare long-term side-effects of proton pump inhibitors (PPIs). The PPIs may inhibit active magnesium (Mg) absorption by interfering with transcellular transient receptor potential melastatin-6 and -7 (TRPM 6 and 7) channels. More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole. After being treated with a range of PPIs, the four patients in our case series developed hypomagnesaemia, which responded to withdrawal of therapy and initiation of Mg replacement. Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long-term use of PPIs. PMID:25138239

Long-term bed degradation in Maryland streams (phase 3, part I) : urban streams in the Piedmont Plateau province.

DOT National Transportation Integrated Search

2014-05-01

Estimation of potential long-term down-cutting of the stream bed is necessary for evaluation and design of bridges for scour and culverts for fish passage. The purpose of this study has been to improve predictions of this potential long-term bed degr...

Self-reported immature defense style as a predictor of outcome in short-term and long-term psychotherapy.

PubMed

Laaksonen, Maarit A; Sirkiä, Carlos; Knekt, Paul; Lindfors, Olavi

2014-07-01

Identification of pretreatment patient characteristics predictive of psychotherapy outcome could help to guide treatment choices. This study evaluates patients' initial level of immature defense style as a predictor of the outcome of short-term versus long-term psychotherapy. In the Helsinki Psychotherapy Study, 326 adult outpatients with mood or anxiety disorder were randomized to individual short-term (psychodynamic or solution-focused) or long-term (psychodynamic) psychotherapy. Their defense style was assessed at baseline using the 88-item Defense Style Questionnaire and classified as low or high around the median value of the respective score. Both specific (Beck Depression Inventory [BDI], Hamilton Depression Rating Scale [HDRS], Symptom Check List Anxiety Scale [SCL-90-Anx], Hamilton Anxiety Rating Scale [HARS]) and global (Symptom Check List Global Severity Index [SCL-90-GSI], Global Assessment of Functioning Scale [GAF]) psychiatric symptoms were measured at baseline and 3-7 times during a 3-year follow-up. Patients with high use of immature defense style experienced greater symptom reduction in long-term than in short-term psychotherapy by the end of the 3-year follow-up (50% vs. 34%). Patients with low use of immature defense style experienced faster symptom reduction in short-term than in long-term psychotherapy during the first year of follow-up (34% vs. 19%). Knowledge of patients' initial level of immature defense style may potentially be utilized in tailoring treatments. Further research on defense styles as outcome predictors in psychotherapies of different types is needed.

The long-term effects of birthing interventions on childhood empathy.

PubMed

Cassels, Tracy G

2014-04-01

birthing practices have changed drastically over the past century. It is now more common for women to birth in a hospital, receive drug interventions, and to birth via caesarean section, yet there is a paucity of research on long-term outcomes associated with practices. The research was designed to determine if there were any long-term effects of the birthing experience on child empathic behaviour. two-hundred-and-sixty-four mother-child dyad (M(child_age)=5.92 years; SD=.85 years; 127 boys) completed either a questionnaire on birthing practices (mothers) or a modified Stickers Task to assess empathic behaviour (child). there was a non-significant effect (Δ=.22, p=.395) of home versus hospital birth and a small-moderate, significant (Δ=.33, p=.017) effect of the use of epidurals during, with children of mothers who did not use an epidural or who birthed at home showing greater empathic behaviour. the birthing location and the decision to have an epidural can have long-term consequences on children's empathy. While researchers need to further examine the mechanisms behind these findings, parents should be made aware of the potential long-term effects in order to allow them to make fully informed decisions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long Periodic Terms in the Solar System

NASA Technical Reports Server (NTRS)

Bretagnon, P.

1982-01-01

The long period variations of the first eight planets in the solar system are studied. First, the Lagrangian solution is calculated and then the long period terms with fourth order eccentricities and inclinations are introduced into the perturbation function. A second approximation was made taking into account the short period terms' contribution, namely the perturbations of first order with respect to the masses. Special attention was paid to the determination of the integration constants. The relative importance of the different contributions is shown. It is useless, for example, to introduce the long period terms of fifth order if no account has been taken of the short period terms. Meanwhile, the terms that have been neglected would not introduce large changes in the integration constants. Even so, the calculation should be repeated with higher order short period terms and fifth order long periods.

Long-Term Hearing Results After Ossiculoplasty.

PubMed

Cox, Matthew D; Trinidade, Aaron; Russell, James Shep; Dornhoffer, John L

2017-04-01

To determine if the OOPS index is predictive of long-term hearing results after ossiculoplasty. Case series with retrospective chart review. Tertiary care otology practice. Adult and pediatric patients (3-88 years of age). Ossiculoplasty with cartilage tympanoplasty, with or without mastoidectomy. Primary outcome measures included short-term hearing results (pure-tone average air-bone gap [PTA-ABG] measured between 60 days and 1 year after surgery), long-term hearing results (PTA-ABG measured ≥5 years after surgery), and the rate of successful ABG closure to ≤20 dB. Secondary measures included the need for revision surgery, delayed tympanic membrane graft failure, worsening conductive hearing loss (after an initially satisfactory hearing result), and recurrence of cholesteatoma. There was no significant difference between adults and children for short-term hearing results (average post-op PTA-ABG was 18.9 dB vs. 19.8 dB, respectively; p = 0.544), long-term hearing results (average final PTA-ABG was 19.3 dB vs. 19.4 dB, respectively; p = 0.922), or rate of ABG closure to less than 20 dB (63.1% vs. 58.0%, p = 0.282). Spearman's rank-order correlation (ρ) identified a strong positive correlation between OOPS index score and average post-operative PTA-ABG (ρ = 0.983; p < 0.001; 2-tailed), as well as average long-term PTA-ABG (ρ = 0.950, p < 0.001; 2-tailed). The OOPS index makes it possible to accurately prognosticate hearing outcomes in adult and pediatric patients undergoing ossiculoplasty in both the short term and the long term.

Short-term memory and long-term memory are still different.

PubMed

Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Short-Term Memory and Long-Term Memory are Still Different

PubMed Central

2017-01-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology—the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as “1, 3, 1” where there are 2 tokens of the digit “1” cannot be stored in the correct order simply by activating the representations of the digits “1” and “3” in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. PMID:28530428

PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories.

PubMed

Grimes, Matthew T; Harley, Carolyn W; Darby-King, Andrea; McLean, John H

2012-02-21

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and translation-dependent). Here, we use neonatal odor-preference learning to explore the role of olfactory bulb PKA in these three phases of mammalian memory. PKA activity increased normally in learning animals 10 min after a single training trial. Inhibition of PKA by Rp-cAMPs blocked intermediate-term and long-term memory, with no effect on short-term memory. PKA inhibition also prevented learning-associated CREB phosphorylation, a transcription factor implicated in long-term memory. When long-term memory was rescued through increased β-adrenoceptor activation, CREB phosphorylation was restored. Intermediate-term and long-term, but not short-term odor-preference memories were generated by pairing odor with direct PKA activation using intrabulbar Sp-cAMPs, which bypasses β-adrenoceptor activation. Higher levels of Sp-cAMPs enhanced memory by extending normal 24-h retention to 48-72 h. These results suggest that increased bulbar PKA is necessary and sufficient for the induction of intermediate-term and long-term odor-preference memory, and suggest that PKA activation levels also modulate memory duration. However, short-term memory appears to use molecular mechanisms other than the PKA/CREB pathway. These mechanisms, which are also recruited by β-adrenoceptor activation, must operate in parallel with PKA activation.

Aging of Dissolved Copper and Copper-based Nanoparticles in Five Different Soils: Short-term Kinetics vs. Long-term Fate

EPA Science Inventory

With the growing availability and use of copper-based nanomaterials (Cu-NMs), there is increasing concern regarding their release and potential impact on the environment. In this study, the short term (≤5 d) aging profile and the long-term (135 d) speciation of dissolved Cu, cop...

Long-Term Soil Chemistry Changes in Aggrading Forest Ecosystems

Treesearch

Jennifer D. Knoepp; Wayne T. Swank

1994-01-01

Assessing potential long-term forest productivity requires identification of the processes regulating chemical changes in forest soils. We resampled the litter layer and upper two mineral soil horizons, A and AB/BA, in two aggrading southern Appalachian watersheds 20 yr after an earlier sampling. Soils from a mixed-hardwood watershed exhibited a small but significant...

Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

PubMed

Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

2015-09-24

Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-term preservation of Leptospira spp.: challenges and prospects.

PubMed

Philip, Noraini; Garba, Bashiru; Neela, Vasantha Kumari

2018-05-08

Preservation of leptospiral cultures is tantamount to success in leptospiral diagnostics, research, and development of preventive strategies. Each Leptospira isolate has imperative value not only in disease diagnosis but also in epidemiology, virulence, pathogenesis, and drug development studies. As the number of circulating leptospires is continuously increasing and congruent with the importance to retain their original characteristics and properties, an efficient long-term preservation is critically needed to be well-established. However, the preservation of Leptospira is currently characterized by difficulties and conflicting results mainly due to the biological nature of this organism. Hence, this review seeks to describe the efforts in developing efficient preservation methods, to discover the challenges in preserving this organism and to identify the factors that can contribute to an effective long-term preservation of Leptospira. Through the enlightenment of the previous studies, a potentially effective method has been suggested. The article also attempts to evaluate novel strategies used in other industrial and biotechnological preservation efforts and consider their potential application to the conservation of Leptospira spp.

Long-Term Stability of Oxide Nanowire Sensors via Heavily Doped Oxide Contact.

PubMed

Zeng, Hao; Takahashi, Tsunaki; Kanai, Masaki; Zhang, Guozhu; He, Yong; Nagashima, Kazuki; Yanagida, Takeshi

2017-12-22

Long-term stability of a chemical sensor is an essential quality for long-term collection of data related to exhaled breath, environmental air, and other sources in the Internet of things (IoT) era. Although an oxide nanowire sensor has shown great potential as a chemical sensor, the long-term stability of sensitivity has not been realized yet due to electrical degradation under harsh sensing conditions. Here, we report a rational concept to accomplish long-term electrical stability of metal oxide nanowire sensors via introduction of a heavily doped metal oxide contact layer. Antimony-doped SnO 2 (ATO) contacts on SnO 2 nanowires show much more stable and lower electrical contact resistance than conventional Ti contacts for high temperature (200 °C) conditions, which are required to operate chemical sensors. The stable and low contact resistance of ATO was confirmed for at least 1960 h under 200 °C in open air. This heavily doped oxide contact enables us to realize the long-term stability of SnO 2 nanowire sensors while maintaining the sensitivity for both NO 2 gas and light (photo) detections. The applicability of our method is confirmed for sensors on a flexible polyethylene naphthalate (PEN) substrate. Since the proposed fundamental concept can be applied to various oxide nanostructures, it will give a foundation for designing long-term stable oxide nanomaterial-based IoT sensors.

Long-term prospects for developments in space: A scenario approach

NASA Technical Reports Server (NTRS)

Brown, W. M.; Kahn, H. D.

1977-01-01

Long-term plans for future NASA programs are reported, and some of the following topics are discussed in detail: (1) systematic formulation of space scenarios; (2) the basic international context; (3) potential 21st century space developments; (4) space vehicle developments; and (5) future exploration.

Long term management practices influenced soil aggregation and carbon dynamics

USDA-ARS?s Scientific Manuscript database

Soil aggregation protects soil organic C (SOC) against rapid decomposition, improves soil quality, and reduces soil erosion potential. The objectives of this study are to evaluate the effects of long-term (21 yrs.) management practices on SOC, water stable aggregate (WSA), and aggregate-associated ...

Short-term exposure to JP-8 jet fuel results in long-term immunotoxicity.

PubMed

Harris, D T; Sakiestewa, D; Robledo, R F; Witten, M

1997-01-01

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed. Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (i.e., physiology, cardiology, respiratory, etc.); e.g., the immune system. Previous studies have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system, which should have serious consequences for the exposed host in terms of susceptibility to infectious agents. If these alterations in immune function were long-lasting, it might also result in an increased likelihood of development and/or progression of cancer, as well as autoimmune disease. In the current study, mice were exposed for 1 h/day for 7 days to a moderate (1000 mg/m3) and a high (2500 mg/m3) concentration of aerosolized JP-8 jet fuel to stimulate occupational exposures. One to 28 days after the last exposure the mice were analyzed for effects of the exposure on their immune systems. It was observed that decrease in viable immune cell numbers and immune organ weights found at 24 h after exposure persisted for extended periods of time. Further, JP-8 exposure resulted in significantly decreased immune infection, as analyzed by mitogenesis assays, which persisted for up to 4 weeks post-exposure. Thus, short-term exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system, which were long-lasting and persistent. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure. Such long-term

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

PubMed

Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

2012-05-01

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

[Potential analysis for research on Advanced Practice Nursing (APN) for persons with dementia living in long-term care facilities].

PubMed

Koch, Sabine; Fleischer, Steffen

2014-01-01

The nursing Minimum Data Set 3.0 (MDS 3.0) and other nursing quality indices summarise relevant health and nursing outcomes for long-term care that are recommended as quality measures. These are measures like "Percent of High-Risk Residents with Pressure Ulcers", "Percent of Low-Risk Residents Who Lose Control of Their Bowels or Bladder", "Percent of Residents Experiencing One or More Falls with Major Injury", "Percent of Residents Who Lose Too Much Weight" etc. Analyses of healthcare data in Germany showed a substantial higher risk for negative outcomes in the long-term care setting in persons with dementia compared to persons without dementia. There already exist evidence-based guidelines and recommendations for most of the quality measures and underlying health problems (e.g., the German "Expertenstandards in der Pflege"). Implementation and translation of evidence have not been systematically researched yet, and there is uncertainty about structures and processes that support implementation and eventually lead to improved nursing outcomes in people with dementia in long-term care. Studies showed a potential benefit of master-level geriatric advanced practice nurses (GAPNs) concerning the implementation of evidence-based guidelines. This corresponds to the expectation that academic nursing staff positively influences research utilisation in practice. A systematic review identified four controlled trials that evaluated the effectiveness of GAPN on select quality measures. Both the internal and external validity of the trials require a thorough investigation into the intervention before translation and effectiveness research in Germany can be recommended. In accordance with national and international recommendations on the development and clinical evaluation of complex interventions, we recommend a multistage model. Such a model comprises the conceptualisation and adaptation of the original intervention. In this way, the original concept of a GAPN has to be

Caregiving and mutuality among long-term colorectal cancer survivors with ostomies: qualitative study.

PubMed

Altschuler, Andrea; Liljestrand, Petra; Grant, Marcia; Hornbrook, Mark C; Krouse, Robert S; McMullen, Carmit K

2018-02-01

The cancer caregiving literature focuses on the early phases of survivorship, but caregiving can continue for decades when cancer creates disability. Survivors with an ostomy following colorectal cancer (CRC) have caregiving needs that may last decades. Mutuality has been identified as a relationship component that can affect caregiving. This paper discusses how mutuality may affect long-term ostomy caregiving. We conducted semi-structured, in-depth interviews with 31 long-term CRC survivors with ostomies and their primary informal caregivers. Interviewees were members of an integrated health care delivery system in the USA. We used inductive theme analysis techniques to analyze the interviews. Most survivors were 71 years of age or older (67%), female (55%), and with some college education (54%). Two thirds lived with and received care from spouses. Caregiving ranged from minimal support to intimate assistance with daily ostomy care. While some survivors received caregiving far beyond what was needed, others did not receive adequate caregiving for their health care needs. Low mutuality created challenges for ostomy caregiving. Mutuality impacts the quality of caregiving, and this quality may change over time, depending on various factors. Emotional feedback and amplification is the proposed mechanism by which mutuality may shift over time. Survivorship care should include assessment and support of mutuality as a resource to enhance health outcomes and quality of life for survivors with long-term caregiving needs and their caregivers. Appropriate questionnaires can be identified or developed to assess mutuality over the survivorship trajectory.

The long-term use of benzodiazepines: patients' views, accounts and experiences.

PubMed

Barter, G; Cormack, M

1996-12-01

Although a decrease in new prescribing has occurred for anxiolytic benzodiazepines, concerns have been raised that a 'core' of long-term users has been left behind. Typically, elderly people represent this 'core', using the benzodiazepines as hypnotics. The present study focuses on the reasons why hypnotic benzodiazepines are used for protracted lengths of time. By examining patient experiences and cognitions, a deeper understanding may be gained of why patients continue to use benzodiazepines. Elderly, long-term users of benzodiazepine hypnotics were interviewed using a semi-structured interview procedure. A comparison group of non-users of the drugs were given a brief interview to collect comparative data. Interview data were analysed from transcripts using qualitative methodology; statistical comparisons between the groups were made using non-parametric statistics. The long-term users had significantly fewer hours of sleep per night than the non-users. There was some evidence of tolerance and a suggestion that symptoms of withdrawal were maintaining continual use. None of the long-term users had clean knowledge of what their doctors thought of their use of benzodiazepines. The data suggest that the power of the doctor may not be utilized to its full potential in the prevention of long-term use, that at least 50% of elderly benzodiazepine users would like to discontinue use, and that patients need information and advice on how to discontinue these drugs.

The importance of supporting autonomy and perceived competence in facilitating long-term tobacco abstinence

PubMed Central

Williams, Geoffrey C.; Niemiec, Christopher P.; Patrick, Heather; Ryan, Richard M.; Deci, Edward L.

2010-01-01

Background The Public Health Service (PHS) Guideline for Treating Tobacco Use and Dependence (1) recommends supporting autonomy and perceived competence to facilitate tobacco abstinence. Purpose To evaluate the effectiveness of an intensive tobacco-dependence intervention based on self-determination theory (SDT) and intended to support autonomy and perceived competence in facilitating long-term tobacco abstinence. Methods One thousand and six adult smokers were recruited into a randomized cessation-induction trial. Community care participants received cessation pamphlets and information on local treatment programs. Intervention participants received the same materials and were asked to meet four times with counselors over six months to discuss their health in a manner intended to support autonomy and perceived competence. The primary outcome was 24-month prolonged abstinence from tobacco. The secondary outcome was 7-day point prevalence tobacco abstinence at 24 months post-intervention. Results Smokers in the intervention were more likely to attain both tobacco abstinence outcomes and these effects were partially mediated by change in both autonomous self-regulation and perceived competence from baseline to six months. Structural equation modeling confirmed the SDT model of health-behavior change in facilitating long-term tobacco abstinence. Conclusions An intervention based on SDT and consistent with the PHS Guideline, which was intended to support autonomy and perceived competence, facilitated long-term tobacco abstinence. PMID:19373517

The importance of supporting autonomy and perceived competence in facilitating long-term tobacco abstinence.

PubMed

Williams, Geoffrey C; Niemiec, Christopher P; Patrick, Heather; Ryan, Richard M; Deci, Edward L

2009-06-01

The Public Health Service (PHS) Guideline for Treating Tobacco Use and Dependence (Fiore et al. 2000) recommends supporting autonomy and perceived competence to facilitate tobacco abstinence. The aim of the study was to evaluate the effectiveness of an intensive tobacco-dependence intervention based on self-determination theory (SDT) and intended to support autonomy and perceived competence in facilitating long-term tobacco abstinence. One thousand and six adult smokers were recruited into a randomized cessation-induction trial. Community care participants received cessation pamphlets and information on local treatment programs. Intervention participants received the same materials and were asked to meet four times with counselors over 6 months to discuss their health in a manner intended to support autonomy and perceived competence. The primary outcome was 24-month prolonged abstinence from tobacco. The secondary outcome was 7-day point prevalence tobacco abstinence at 24 months postintervention. Smokers in the intervention were more likely to attain both tobacco abstinence outcomes and these effects were partially mediated by change in both autonomous self-regulation and perceived competence from baseline to 6 months. Structural equation modeling confirmed the SDT model of health-behavior change in facilitating long-term tobacco abstinence. An intervention based on SDT and consistent with the PHS Guideline, which was intended to support autonomy and perceived competence, facilitated long-term tobacco abstinence.

Discovering long-term potentiation (LTP) - recollections and reflections on what came after.

PubMed

Lømo, T

2018-02-01

Chance events led me to a lifelong career in scientific research. They paved the way for being the first to see long-term potentiation of synaptic efficiency (LTP) in Per Andersen's laboratory in Oslo in 1966. Here I describe my way to this discovery and the experiments with Tim Bliss in 1968-1969 that led to Bliss and Lømo, 1973. Surprisingly, we later failed to reproduce these results. I discuss possible reasons for this failure, which made us both leave LTP research, in my case for good, in Tim's case for several years. After 30 years of work in a different field, I renewed my interest in the hippocampus and LTP in the early 2000s and published, for the first time, results that I had obtained 40 years earlier. Here I present my take on how interest in and research on LTP evolved after the early years. This includes a discussion of the functions of hippocampus as seen in those early days, the case of patient H.M., Donald Hebb's place in the story, the search for 'memory molecules' such as PKMζ, and the primary site for LTP expression (pre- and/or post-synaptic?). Throughout, I reflect on my life in science, how science is done and what drives it. The reflections are quite personal and I admit to mixed feelings about broadcasting them. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

PubMed

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

PubMed

Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

2015-11-01

Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala. © 2015 International

Long-term depression of inhibitory synaptic transmission induced by spike-timing dependent plasticity requires coactivation of endocannabinoid and muscarinic receptors.

PubMed

Ahumada, Juan; Fernández de Sevilla, David; Couve, Alejandro; Buño, Washington; Fuenzalida, Marco

2013-12-01

The precise timing of pre-postsynaptic activity is vital for the induction of long-term potentiation (LTP) or depression (LTD) at many central synapses. We show in synapses of rat CA1 pyramidal neurons in vitro that spike timing dependent plasticity (STDP) protocols that induce LTP at glutamatergic synapses can evoke LTD of inhibitory postsynaptic currents or STDP-iLTD. The STDP-iLTD requires a postsynaptic Ca(2+) increase, a release of endocannabinoids (eCBs), the activation of type-1 endocananabinoid receptors and presynaptic muscarinic receptors that mediate a decreased probability of GABA release. In contrast, the STDP-iLTD is independent of the activation of nicotinic receptors, GABAB Rs and G protein-coupled postsynaptic receptors at pyramidal neurons. We determine that the downregulation of presynaptic Cyclic adenosine monophosphate/protein Kinase A pathways is essential for the induction of STDP-iLTD. These results suggest a novel mechanism by which the activation of cholinergic neurons and retrograde signaling by eCBs can modulate the efficacy of GABAergic synaptic transmission in ways that may contribute to information processing and storage in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

Acid Mine Drainage Passive Remediation: Potential Use of Alkaline Clay, Optimal Mixing Ratio and Long Term Impacts

NASA Astrophysics Data System (ADS)

Plaza, F.; Liang, X.; Wen, Y.; Perone, H.

2015-12-01

Acid mine drainage (AMD) is one of the most adverse environmental problems of the mine industry. Surface water and ground water affected by this pollution are characterized by their acidity and the high content of sulfates and heavy metals. In this study, alkaline clay, an industrial waste with a high pH, which is utilized in the alumina refining process, was used as the remediation material to inhibit pyrite oxidation. Through a series of batch and column experiments, complemented with field measurements and geochemical modeling, three important issues associated with this passive and auto sustainable acid mine drainage remediation method were investigated: 1) the potential use of alkaline clay as an AMD remediation material, 2) the adequate alkaline clay/coal refuse mixing ratio (AC/CR) to ensure pH values near to neutral conditions, and, 3) the prediction of long term impacts, in terms of the trends of the main parameters involved in this process such as pH, concentrations of sulfate, iron and other dissolved contaminants. Both field measurements and the samples used for the experiments came from a coal waste site located in Mather, Pennsylvania. Alkaline clay proved to be an effective remediation material for AMD. It was found that 10% AC/CR is an adequate mixing ratio (i.e. the upper limit), which has been also indicated by field measurements. The concentrations of some contaminants such as iron, manganese or sulfate are significantly reduced with the remediation approach, compared to those representative concentrations found in mine tailings. Moreover, results suggest a very reliable long-term stability of the remediation (i.e. neutral pH conditions are maintained), thus enhancing the generation of iron precipitates that could produce pyrite grain coating and hardpan (i.e. cemented layer) on the surface. These processes also made the amended layer less porous, thus increasing water retention and hindering oxygen diffusion.

Long-term exposure to particulate matter, NO2 and the oxidative potential of particulates and diabetes prevalence in a large national health survey.

PubMed

Strak, Maciej; Janssen, Nicole; Beelen, Rob; Schmitz, Oliver; Vaartjes, Ilonca; Karssenberg, Derek; van den Brink, Carolien; Bots, Michiel L; Dijst, Martin; Brunekreef, Bert; Hoek, Gerard

2017-11-01

The evidence from observational epidemiological studies of a link between long-term air pollution exposure and diabetes prevalence and incidence is currently mixed. Some studies found the strongest associations of diabetes with fine particles, other studies with nitrogen dioxide and some studies found no associations. Our aim was to investigate associations between long-term exposure to multiple air pollutants and diabetes prevalence in a large national survey in the Netherlands. We performed a cross-sectional analysis using the 2012 Dutch national health survey to investigate the associations between the 2009 annual average concentrations of multiple air pollutants (PM 10 , PM 2.5 , PM 10-2.5 , PM 2.5 absorbance, OP DTT , OP ESR and NO 2 ) and diabetes prevalence, among 289,703 adults. Air pollution exposure was assessed by land use regression models. Diabetes was defined based on a combined measure of self-reported physician diagnosis and medication prescription from an external database. Using logistic regression, we adjusted for potential confounders, including neighborhood- and individual socio-economic status and lifestyle-related risk factors such as smoking habits, alcohol consumption, physical activity and BMI. After adjustment for potential confounders, all pollutants (except PM 2.5 ) were associated with diabetes prevalence. In two-pollutant models, NO 2 and OP DTT remained associated with increased diabetes prevalence. For NO 2 and OP DTT , single-pollutant ORs per interquartile range were 1.07 (95% CI: 1.05, 1.09) and 1.08 (95% CI: 1.05, 1.10), respectively. Stratified analysis showed no consistent effect modification by any of the included known diabetes risk factors. Long-term residential air pollution exposure was associated with diabetes prevalence in a large health survey in the Netherlands, strengthening the evidence of air pollution being an important diabetes risk factor. Most consistent associations were observed for NO 2 and oxidative

Complex network structure influences processing in long-term and short-term memory.

PubMed

Vitevitch, Michael S; Chan, Kit Ying; Roodenrys, Steven

2012-07-01

Complex networks describe how entities in systems interact; the structure of such networks is argued to influence processing. One measure of network structure, clustering coefficient, C, measures the extent to which neighbors of a node are also neighbors of each other. Previous psycholinguistic experiments found that the C of phonological word-forms influenced retrieval from the mental lexicon (that portion of long-term memory dedicated to language) during the on-line recognition and production of spoken words. In the present study we examined how network structure influences other retrieval processes in long- and short-term memory. In a false-memory task-examining long-term memory-participants falsely recognized more words with low- than high-C. In a recognition memory task-examining veridical memories in long-term memory-participants correctly recognized more words with low- than high-C. However, participants in a serial recall task-examining redintegration in short-term memory-recalled lists comprised of high-C words more accurately than lists comprised of low-C words. These results demonstrate that network structure influences cognitive processes associated with several forms of memory including lexical, long-term, and short-term.

Self-reported immature defense style as a predictor of outcome in short-term and long-term psychotherapy

PubMed Central

Laaksonen, Maarit A; Sirkiä, Carlos; Knekt, Paul; Lindfors, Olavi

2014-01-01

Objective Identification of pretreatment patient characteristics predictive of psychotherapy outcome could help to guide treatment choices. This study evaluates patients' initial level of immature defense style as a predictor of the outcome of short-term versus long-term psychotherapy. Method In the Helsinki Psychotherapy Study, 326 adult outpatients with mood or anxiety disorder were randomized to individual short-term (psychodynamic or solution-focused) or long-term (psychodynamic) psychotherapy. Their defense style was assessed at baseline using the 88-item Defense Style Questionnaire and classified as low or high around the median value of the respective score. Both specific (Beck Depression Inventory [BDI], Hamilton Depression Rating Scale [HDRS], Symptom Check List Anxiety Scale [SCL-90-Anx], Hamilton Anxiety Rating Scale [HARS]) and global (Symptom Check List Global Severity Index [SCL-90-GSI], Global Assessment of Functioning Scale [GAF]) psychiatric symptoms were measured at baseline and 3–7 times during a 3-year follow-up. Results Patients with high use of immature defense style experienced greater symptom reduction in long-term than in short-term psychotherapy by the end of the 3-year follow-up (50% vs. 34%). Patients with low use of immature defense style experienced faster symptom reduction in short-term than in long-term psychotherapy during the first year of follow-up (34% vs. 19%). Conclusion Knowledge of patients' initial level of immature defense style may potentially be utilized in tailoring treatments. Further research on defense styles as outcome predictors in psychotherapies of different types is needed. PMID:25161816

Long-term environmental monitoring for assessment of change: measurement inconsistencies over time and potential solutions.

PubMed

Ellingsen, Kari E; Yoccoz, Nigel G; Tveraa, Torkild; Hewitt, Judi E; Thrush, Simon F

2017-10-30

The importance of long-term environmental monitoring and research for detecting and understanding changes in ecosystems and human impacts on natural systems is widely acknowledged. Over the last decades, a number of critical components for successful long-term monitoring have been identified. One basic component is quality assurance/quality control protocols to ensure consistency and comparability of data. In Norway, the authorities require environmental monitoring of the impacts of the offshore petroleum industry on the Norwegian continental shelf, and in 1996, a large-scale regional environmental monitoring program was established. As a case study, we used a sub-set of data from this monitoring to explore concepts regarding best practices for long-term environmental monitoring. Specifically, we examined data from physical and chemical sediment samples and benthic macroinvertebrate assemblages from 11 stations from six sampling occasions during the period 1996-2011. Despite the established quality assessment and quality control protocols for this monitoring program, we identified several data challenges, such as missing values and outliers, discrepancies in variable and station names, changes in procedures without calibration, and different taxonomic resolution. Furthermore, we show that the use of different laboratories over time makes it difficult to draw conclusions with regard to some of the observed changes. We offer recommendations to facilitate comparison of data over time. We also present a new procedure to handle different taxonomic resolution, so valuable historical data is not discarded. These topics have a broader relevance and application than for our case study.

A Suprachoroidal Electrical Retinal Stimulator Design for Long-Term Animal Experiments and In Vivo Assessment of Its Feasibility and Biocompatibility in Rabbits

PubMed Central

Zhou, J. A.; Woo, S. J.; Park, S. I.; Kim, E. T.; Seo, J. M.; Chung, H.; Kim, S. J.

2008-01-01

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes. PMID:18317521

Long-term high-intensity sound stimulation inhibits h current (Ih ) in CA1 pyramidal neurons.

PubMed

Cunha, A O S; Ceballos, C C; de Deus, J L; Leão, R M

2018-05-19

Afferent neurotransmission to hippocampal pyramidal cells can lead to long-term changes to their intrinsic membrane properties and affect many ion currents. One of the most plastic neuronal currents is the hyperpolarization activated cationic current (I h ), which changes in CA1 pyramidal cells in response to many types of physiological and pathological processes, including auditory stimulation. Recently we demonstrated that long-term potentiation (LTP) in rat hippocampal Schaffer-CA1 synapses is depressed by high-intensity sound stimulation. Here we investigated if a long-term high-intensity sound stimulation could affect intrinsic membrane properties of rat CA1 pyramidal neurons. Our results showed that I h is depressed by long-term high intensity sound exposure (1 minute of 110 dB sound, applied two times per day for 10 days). This resulted in a decreased resting membrane potential, increased membrane input resistance and time constant, and decreased action potential threshold. In addition, CA1 pyramidal neurons from sound-exposed animals fired more action potentials than neurons from control animals; However, this effect was not caused by a decreased I h . Interestingly, a single episode (1 minute) of 110 dB sound stimulation which also inhibits hippocampal LTP did not affect I h and firing in pyramidal neurons, suggesting that effects on I h are long-term responses to high intensity sound exposure. Our results show that prolonged exposure to high-intensity sound affects intrinsic membrane properties of hippocampal pyramidal neurons, mainly by decreasing the amplitude of I h . This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Using electrophysiology to demonstrate that cuing affects long-term memory storage over the short term

PubMed Central

Maxcey, Ashleigh M.; Fukuda, Keisuke; Song, Won S.; Woodman, Geoffrey F.

2015-01-01

As researchers who study working memory, we often assume that participants keep a representation of an object in working memory when we present a cue that indicates that object will be tested in a couple of seconds. This intuitively accounts for how well people can remember a cued object relative to their memory for that same object presented without a cue. However, it is possible that this superior memory does not purely reflect storage of the cued object in working memory. We tested the hypothesis that cued presented during a stream of objects, followed by a short retention interval and immediate memory test, change how information is handled by long-term memory. We tested this hypothesis using a family of frontal event-related potentials (ERPs) believed to reflect long-term memory storage. We found that these frontal indices of long-term memory were sensitive to the task relevance of objects signaled by auditory cues, even when objects repeat frequently such that proactive interference was high. Our findings indicate the problematic nature of assuming process purity in the study of working memory, and demonstrate how frequent stimulus repetitions fail to isolate the role of working memory mechanisms. PMID:25604772

Using electrophysiology to demonstrate that cueing affects long-term memory storage over the short term.

PubMed

Maxcey, Ashleigh M; Fukuda, Keisuke; Song, Won S; Woodman, Geoffrey F

2015-10-01

As researchers who study working memory, we often assume that participants keep a representation of an object in working memory when we present a cue that indicates that the object will be tested in a couple of seconds. This intuitively accounts for how well people can remember a cued object, relative to their memory for that same object presented without a cue. However, it is possible that this superior memory does not purely reflect storage of the cued object in working memory. We tested the hypothesis that cues presented during a stream of objects, followed by a short retention interval and immediate memory test, can change how information is handled by long-term memory. We tested this hypothesis by using a family of frontal event-related potentials believed to reflect long-term memory storage. We found that these frontal indices of long-term memory were sensitive to the task relevance of objects signaled by auditory cues, even when the objects repeated frequently, such that proactive interference was high. Our findings indicate the problematic nature of assuming process purity in the study of working memory, and demonstrate that frequent stimulus repetitions fail to isolate the role of working memory mechanisms.

Predicting Discharge to Institutional Long-Term Care After Stroke: A Systematic Review and Metaanalysis.

PubMed

Burton, Jennifer K; Ferguson, Eilidh E C; Barugh, Amanda J; Walesby, Katherine E; MacLullich, Alasdair M J; Shenkin, Susan D; Quinn, Terry J

2018-01-01

Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. Acute and rehabilitation hospitals. Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. Factors associated with new institutionalization. From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting. �

Health Effects in Fish of Long-Term Exposure to Effluents from Wastewater Treatment Works

PubMed Central

Liney, Katherine E.; Hagger, Josephine A.; Tyler, Charles R.; Depledge, Michael H.; Galloway, Tamara S.; Jobling, Susan

2006-01-01

Concern has been raised in recent years that exposure to wastewater treatment effluents containing estrogenic chemicals can disrupt the endocrine functioning of riverine fish and cause permanent alterations in the structure and function of the reproductive system. Reproductive disorders may not necessarily arise as a result of estrogenic effects alone, and there is a need for a better understanding of the relative importance of endocrine disruption in relation to other forms of toxicity. Here, the integrated health effects of long-term effluent exposure are reported (reproductive, endocrine, immune, genotoxic, nephrotoxic). Early life-stage roach, Rutilus rutilus, were exposed for 300 days to treated wastewater effluent at concentrations of 0, 15.2, 34.8, and 78.7% (with dechlorinated tap water as diluent). Concentrations of treated effluents that induced feminization of male roach, measured as vitellogenin induction and histological alteration to gonads, also caused statistically significant alterations in kidney development (tubule diameter), modulated immune function (differential cell count, total number of thrombocytes), and caused genotoxic damage (micronucleus induction and single-strand breaks in gill and blood cells). Genotoxic and immunotoxic effects occurred at concentrations of wastewater effluent lower than those required to induce recognizable changes in the structure and function of the reproductive endocrine system. These findings emphasize the need for multiple biological end points in tests that assess the potential health effects of wastewater effluents. They also suggest that for some effluents, genotoxic and immune end points may be more sensitive than estrogenic (endocrine-mediated) end points as indicators of exposure in fish. PMID:16818251

Evaluation of Maternal and Perinatal Outcomes of Induction in Borderline Oligohydramnios at Term.

PubMed

Rathod, Setu; Samal, Sunil Kumar

2017-09-01

Oligohydramnios is described as decreased amniotic fluid volume relative to gestational age. Semiquantitatively it is described using the Amniotic Fluid Index (AFI) which is calculated by adding the depth in centimetres of the largest vertical pocket in each of four equal uterine quadrants. AFI less than or equal to 5 cm is defined as oligohydramnios. A Borderline Oligohydramnios (BO) is defined as AFI 5.1-8 cm. To assess the maternal and perinatal outcome of induction in borderline oligohydramnios cases at term. This is a retrospective observational study done from December 2015 to November 2016 in Mahatma Gandhi Medical College and Research Institute, Puducherry, India. Fifty cases of BO with AFI 5.1 cm - 8 cm taken as case and another 50 cases of Normal Liquor (NL) with AFI 8.1 cm - 18 cm taken as control. Data was collected and analysed by SPSS software version 20.0 For qualitative data, the χ 2 -test or Fisher's-exact test were used and for continuous variables, the t-test was used. Cases and controls were matched in baseline parameters. More number of cases were found with meconium stained liquor during labour which is statistically significant (p<0.05). Otherwise there were no statistical significant difference between cases and controls in maternal and perinatal outcome. Induction of labour in cases with BO cases compared to those with NL at term did not show very statistically significant difference in terms of induction to delivery interval and neonatal outcome.

78 FR 66945 - Proposed Collection; 60-Day Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY) Summary: In compliance with the requirement... days of the date of this publication. Proposed Collection: Gulf Long-Term Follow-Up Study (GuLF STUDY... GuLF STUDY is to investigate potential short- and long-term health effects associated with oil spill...

Small mammals as indicators of short-term and long-term disturbance in mixed prairie

USGS Publications Warehouse

Leis, S.A.; Leslie, David M.; Engle, David M.; Fehmi, J.S.

2008-01-01

Disturbance by military maneuvers over short and long time scales may have differential effects on grassland communities. We assessed small mammals as indicators of disturbance by military maneuvers in a mixed prairie in southern Oklahoma USA. We examined sites on two soil series, Foard and Lawton, across a gradient of disturbance intensity. A MANOVA showed that abundance of small mammals was associated (p = 0.03) with short-term (cover of vehicle tracks) disturbance but was not associated (p = 0.12) with long-term (loss of soil organic carbon, SOC) disturbance intensity. At the individual species level, Sigmodon hispidus (cotton rat) and Peromyscus maniculatus (deer mouse) occurred across all levels of disturbance and in both soil types. Only P. maniculatus abundance changed (p < 0.01) with short-term disturbance and increased by about one individual per 5% of additional track-cover. Abundance of P. maniculatus also increased (p = 0.04) by about three individuals per 1% increase in soil carbon. Chaetodipus hispidus (hispid pocket mouse) and Reithrodontomys fulvescens (fulvous harvest mouse) only occurred in single soil types limiting their potential as more general indicators. Abundance of P. maniculatus was positively related to shifts in plant species composition and likely reflected changes in vegetation structure (i.e. litter depth) and forage availability resulting from disturbance. Peromyscus maniculatus may be a useful biological indicator of ecosystem change because it responded predictably to both long-term and short-term disturbance and, when coupled with soil, plant, and disturbance history variables, can reveal land condition trends. ?? Springer Science+Business Media B.V. 2007.

Global estimation of long-term persistence in annual river runoff

NASA Astrophysics Data System (ADS)

Markonis, Y.; Moustakis, Y.; Nasika, C.; Sychova, P.; Dimitriadis, P.; Hanel, M.; Máca, P.; Papalexiou, S. M.

2018-03-01

Long-term persistence (LTP) of annual river runoff is a topic of ongoing hydrological research, due to its implications to water resources management. Here, we estimate its strength, measured by the Hurst coefficient H, in 696 annual, globally distributed, streamflow records with at least 80 years of data. We use three estimation methods (maximum likelihood estimator, Whittle estimator and least squares variance) resulting in similar mean values of H close to 0.65. Subsequently, we explore potential factors influencing H by two linear (Spearman's rank correlation, multiple linear regression) and two non-linear (self-organizing maps, random forests) techniques. Catchment area is found to be crucial for medium to larger watersheds, while climatic controls, such as aridity index, have higher impact to smaller ones. Our findings indicate that long-term persistence is weaker than found in other studies, suggesting that enhanced LTP is encountered in large-catchment rivers, were the effect of spatial aggregation is more intense. However, we also show that the estimated values of H can be reproduced by a short-term persistence stochastic model such as an auto-regressive AR(1) process. A direct consequence is that some of the most common methods for the estimation of H coefficient, might not be suitable for discriminating short- and long-term persistence even in long observational records.

Priming of Short-Term Potentiation and Synaptic Tagging/Capture Mechanisms by Ryanodine Receptor Activation in Rat Hippocampal CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Li, Qin; Abraham, Wickliffe C.; Xiao, Zhi Cheng

2009-01-01

Activity-dependent changes in synaptic strength such as long-term potentiation (LTP) and long-term depression (LTD) are considered to be cellular mechanisms underlying learning and memory. Strengthening of a synapse for a few seconds or minutes is termed short-term potentiation (STP) and is normally unable to take part in the processes of synaptic…

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends.

PubMed

Ojanen, Sami P; Nieminen, Marko; Meyke, Evgeniy; Pöyry, Juha; Hanski, Ilkka

2013-10-01

Long-term observational studies conducted at large (regional) spatial scales contribute to better understanding of landscape effects on population and evolutionary dynamics, including the conditions that affect long-term viability of species, but large-scale studies are expensive and logistically challenging to keep running for a long time. Here, we describe the long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia) that has been conducted since 1991 in a large network of 4000 habitat patches (dry meadows) within a study area of 50 by 70 km in the Åland Islands in Finland. We explain how the landscape structure has been described, including definition, delimitation, and mapping of the habitat patches; methods of field survey, including the logistics, cost, and reliability of the survey; and data management using the EarthCape biodiversity platform. We describe the long-term metapopulation dynamics of the Glanville fritillary based on the survey. There has been no long-term change in the overall size of the metapopulation, but the level of spatial synchrony and hence the amplitude of fluctuations in year-to-year metapopulation dynamics have increased over the years, possibly due to increasing frequency of exceptional weather conditions. We discuss the added value of large-scale and long-term population studies, but also emphasize the need to integrate more targeted experimental studies in the context of long-term observational studies. For instance, in the case of the Glanville fritillary project, the long-term study has produced an opportunity to sample individuals for experiments from local populations with a known demographic history. These studies have demonstrated striking differences in dispersal rate and other life-history traits of individuals from newly established local populations (the offspring of colonizers) versus individuals from old, established local populations. The long-term observational study has stimulated the

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends

PubMed Central

Ojanen, Sami P; Nieminen, Marko; Meyke, Evgeniy; Pöyry, Juha; Hanski, Ilkka

2013-01-01

Long-term observational studies conducted at large (regional) spatial scales contribute to better understanding of landscape effects on population and evolutionary dynamics, including the conditions that affect long-term viability of species, but large-scale studies are expensive and logistically challenging to keep running for a long time. Here, we describe the long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia) that has been conducted since 1991 in a large network of 4000 habitat patches (dry meadows) within a study area of 50 by 70 km in the Åland Islands in Finland. We explain how the landscape structure has been described, including definition, delimitation, and mapping of the habitat patches; methods of field survey, including the logistics, cost, and reliability of the survey; and data management using the EarthCape biodiversity platform. We describe the long-term metapopulation dynamics of the Glanville fritillary based on the survey. There has been no long-term change in the overall size of the metapopulation, but the level of spatial synchrony and hence the amplitude of fluctuations in year-to-year metapopulation dynamics have increased over the years, possibly due to increasing frequency of exceptional weather conditions. We discuss the added value of large-scale and long-term population studies, but also emphasize the need to integrate more targeted experimental studies in the context of long-term observational studies. For instance, in the case of the Glanville fritillary project, the long-term study has produced an opportunity to sample individuals for experiments from local populations with a known demographic history. These studies have demonstrated striking differences in dispersal rate and other life-history traits of individuals from newly established local populations (the offspring of colonizers) versus individuals from old, established local populations. The long-term observational study has stimulated the

Medical Underwriting In Long-Term Care Insurance: Market Conditions Limit Options For Higher-risk Consumers

PubMed Central

2016-01-01

A key feature of private long-term care insurance is that medical underwriters screen out would-be buyers who have health conditions that portend near-term physical or cognitive disability. We applied common underwriting criteria based on data from two long-term care insurers to a nationally representative sample of individuals in the target age range for long-term care insurance (50–71 years of age). The screening criteria put upper bounds on the current proportion of Americans who could gain coverage in the individual market without changes to medical underwriting practice. Specifically, our simulations show that, for the target age range, approximately 30% of individuals whose wealth meets minimum industry standards for the suitability of long-term care insurance would have their long-term care insurance application rejected for medical reasons. Among the general population–without considering restrictions on wealth–we estimate that 40% would be disqualified. In evaluating long-term care financing reforms and their potential to increase private insurance rates, as well as to reduce financial pressure on public safety-net programs, policymakers need to consider the role of underwriting in the market for long-term care insurance. PMID:27503976

Emotional and Cognitive Information Processing: Relations to Behavioral Performance and Hippocampal Long-Term Potentiation In Vivo during a Spatial Water Maze Training in Rats

ERIC Educational Resources Information Center

Schulz, Kristina; Korz, Volker

2010-01-01

Emotionality as well as cognitive abilities contribute to the acquisition and retrieval of memories as well as to the consolidation of long-term potentiation (LTP), a cellular model of memory formation. However, little is known about the timescale and relative contribution of these processes. Therefore, we tested the effects of weak water maze…

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.

Hormonal and Monoamine Signaling during Reinforcement of Hippocampal Long-Term Potentiation and Memory Retrieval

ERIC Educational Resources Information Center

Korz, Volker; Frey, Julietta U.

2007-01-01

Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems…

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,…

Exploring views on long term rehabilitation for people with stroke in a developing country: findings from focus group discussions

PubMed Central

2014-01-01

Background The importance of long term rehabilitation for people with stroke is increasingly evident, yet it is not known whether such services can be materialised in countries with limited community resources. In this study, we explored the perception of rehabilitation professionals and people with stroke towards long term stroke rehabilitation services and potential approaches to enable provision of these services. Views from providers and users are important in ensuring whatever strategies developed for long term stroke rehabilitations are feasible and acceptable. Methods Focus group discussions were conducted involving 15 rehabilitation professionals and eight long term stroke survivors. All recorded conversations were transcribed verbatim and analysed using the principles of qualitative research. Results Both groups agreed that people with stroke may benefit from more rehabilitation compared to the amount of rehabilitation services presently provided. Views regarding the unavailability of long term rehabilitation services due to multi-factorial barriers were recognised. The groups also highlighted the urgent need for the establishment of community-based stroke rehabilitation centres. Family-assisted home therapy was viewed as a potential approach to continued rehabilitation for long term stroke survivors, given careful planning to overcome several family-related issues. Conclusions Barriers to the provision of long term stroke rehabilitation services are multi-factorial. Establishment of community-based stroke rehabilitation centres and training family members to conduct home-based therapy are two potential strategies to enable the continuation of rehabilitation for long term stroke survivors. PMID:24606911

The Induction Mentor Voice: A Phenomenological Study of Effective Practices for High Quality K-12 Teacher Induction Mentoring

ERIC Educational Resources Information Center

Doering, Sagui Araceli

2018-01-01

In education, mentoring is pivotal in the early development and long-term success and self-directed efficacy of new teachers. With increasing acknowledgment of the importance of mentoring as the preferred means of induction support for new teachers, mentors can serve to positively impact the overall quality of teaching and learning. Yet, like the…

Long-term studies of dopamine agonists.

PubMed

Hubble, Jean P

2002-02-26

Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

Long-term Autophagy and Nrf2 Signaling in the Hippocampi of Developing Mice after Carbon Ion Exposure

PubMed Central

Ye, Fei; Zhao, Ting; Liu, Xiongxiong; Jin, Xiaodong; Liu, Xinguo; Wang, Tieshan; Li, Qiang

2015-01-01

To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi. Secondary X-ray insult was adopted to amplify potential damages. Long-term behavioral changes were observed in high-LET carbon ion-irradiated mice. There were no differences in the rates of LC3-II induction and p62/SQSTM1 degradation compared to the control group regardless of whether the mice received the secondary X-ray insult. A high nuclear Nrf2 content and low apoptosis level in hippocampal cells subjected to secondary X-rays were observed for the mice exposed to relatively low-LET carbon ions. Therefore, carbon ion exposure in the immature mouse led to an LET-dependent behavioral change after maturation. Although autophagy was intact, the persistently high nuclear Nrf2 content in the hippocampus might account for the unchanged behavioral pattern in mice exposed to the relatively low-LET carbon ions and the subsequent increased radioresistance of the hippocampus. PMID:26689155

Internet Interventions for Long-Term Conditions: Patient and Caregiver Quality Criteria

PubMed Central

Murray, Elizabeth; Stevenson, Fiona; Gore, Charles; Nazareth, Irwin

2006-01-01

Background Interactive health communication applications (IHCAs) that combine high-quality health information with interactive components, such as self-assessment tools, behavior change support, peer support, or decision support, are likely to benefit people with long-term conditions. IHCAs are now largely Web-based and are becoming known as "Internet interventions." Although there are numerous professionally generated criteria to assess health-related websites, to date there has been scant exploration of patient-generated assessment criteria even though patients and professionals use different criteria for assessing the quality of traditional sources of health information. Objective We aimed to determine patients' and caregivers' requirements of IHCAs for long-term conditions as well as their criteria for assessing the quality of different programs. Methods This was a qualitative study with focus groups. Patients and caregivers managing long-term conditions used three (predominantly Web-based) IHCAs relevant to their condition and subsequently discussed the strengths and weaknesses of the different IHCAs in focus groups. Participants in any one focus group all shared the same long-term condition and viewed the same three IHCAs. Patient and caregiver criteria for IHCAs emerged from the data. Results There were 40 patients and caregivers who participated in 10 focus groups. Participants welcomed the potential of Internet interventions but felt that many were not achieving their full potential. Participants generated detailed and specific quality criteria relating to information content, presentation, interactivity, and trustworthiness, which can be used by developers and purchasers of Internet interventions. Conclusions The user-generated quality criteria reported in this paper should help developers and purchasers provide Internet interventions that better meet user needs. PMID:16954123

Academic potential and cognitive functioning of long-term survivors after childhood liver transplantation.

PubMed

Ee, L C; Lloyd, O; Beale, K; Fawcett, J; Cleghorn, G J

2014-05-01

This cross-sectional study assessed intellect, cognition, academic function, behaviour, and emotional health of long-term survivors after childhood liver transplantation. Eligible children were >5 yr post-transplant, still attending school, and resident in Queensland. Hearing and neurocognitive testing were performed on 13 transplanted children and six siblings including two twin pairs where one was transplanted and the other not. Median age at testing was 13.08 (range 6.52-16.99) yr; time elapsed after transplant 10.89 (range 5.16-16.37) yr; and age at transplant 1.15 (range 0.38-10.00) yr. Mean full-scale IQ was 97 (81-117) for transplanted children and 105 (87-130) for siblings. No difficulties were identified in intellect, cognition, academic function, and memory and learning in transplanted children or their siblings, although both groups had reduced mathematical ability compared with normal. Transplanted patients had difficulties in executive functioning, particularly in self-regulation, planning and organization, problem-solving, and visual scanning. Thirty-one percent (4/13) of transplanted patients, and no siblings, scored in the clinical range for ADHD. Emotional difficulties were noted in transplanted patients but were not different from their siblings. Long-term liver transplant survivors exhibit difficulties in executive function and are more likely to have ADHD despite relatively intact intellect and cognition. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to long-term potentiation and spatial learning.

PubMed

Nanou, Evanthia; Scheuer, Todd; Catterall, William A

2016-11-15

Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca 2+ type 2.1 (Ca V 2.1) channels. However, the contribution of regulation of Ca V 2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of Ca V 2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg 2+ The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of Ca V 2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.

New Perspectives on the Affordability of Long-Term Care Insurance and Potential Market Size.

ERIC Educational Resources Information Center

Cohen, Marc A.; And Others

1993-01-01

Examined over 6,000 elderly long-term care insurance purchasers. Found that typical policy sold cost $102 per month, covered five years of nursing home care and paid $69 per day in benefits. Close to one-third of purchasers had incomes under $20,000, 63% used some savings to pay premiums, 37% spent more than 5% of income on policies. (Author/NB)

Early nutrition and health: short- and long-term outcomes.

PubMed

Gruszfeld, Dariusz; Socha, Piotr

2013-01-01

Maternal diet, nutritional status during pregnancy, and the early diet of the offspring play an important role in later health. The short- and long-term outcomes of early nutrition have been extensively studied in recent decades. One of the most commonly investigated nutritional interventions is breastfeeding, which is associated with a number of positive short- and long-term outcomes. A short-term effect of breastfeeding is reduced morbidity and mortality in children from poor living conditions and in preterm infants. Breastfeeding is associated with better cognitive development and also has a long-term protective effect on obesity risk, prevalence of type 2 diabetes, and a lowering effect on blood pressure. Selected nutrients have undergone extensive investigation to show their role in disease prevention or improved development, e.g. protein intake in infancy seems to be associated with a later risk of obesity or docosahexaenoic acid supplementation has a positive impact on cognitive function. Another consideration is the fast catch-up growth in small for gestational age infants as an important factor associated with adult risk of cardiovascular problems. On the other hand, high protein and energy intake seems to be positively associated with some indicators of cognitive development. Most of the evidence comes from observational studies that cannot exclude potential confounders. Animal studies demonstrate causality but should not be directly extrapolated to humans. The number of randomized controlled studies is increasing but long-term follow-ups are necessary to obtain convincing results. The majority of these trials compare different infant formula compositions and macro- or micronutrient supplementation. One of the major questions is to define a critical (or opportunity) window and a mechanism of nutritional influence on several health outcomes. Copyright © 2013 S. Karger AG, Basel.

Off the rails in rural South Carolina: a qualitative study of healthcare provider perspectives on the long-term health impact of the Graniteville train disaster.

PubMed

Annang Ingram, Lucy; Tinago, Chiwoneso B; Estrada, Robin; Wilson, Sacoby; Wright Sanders, Louisiana; Bevington, Tina; Carlos, Bethany; Cornelius, Evangeline; Svendsen, Erik R; Ball, Julia

2016-01-01

In 2005, a train derailment and subsequent chlorine spill ravaged the rural town of Graniteville in South Carolina, resulting in one of the worst chlorine gas exposures in US. Significant health and economic challenges persist in the community more than a decade later. Healthcare providers offered healthcare services to community members in the immediate aftermath of the disaster, and many still live in the community and continue to provide healthcare services. As such, healthcare professionals provide a unique and important perspective to help understand the impact of the disaster on the community's health. The purpose of this study was to explore healthcare providers' perspectives about the long-term effects of the disaster on community health, healthcare access, and wellbeing. Semi-structured interviews were conducted with 30 healthcare providers who treated survivors of the Graniteville train disaster. A qualitative, essentialist, inductive thematic analytic approach was used to analyze study data. Four themes emerged regarding the disaster's long-term impact: effects of chlorine exposure on physical health, issues with healthcare access, residual effects of the disaster on personal and community wellbeing, and improving health and community wellbeing. Disaster recovery should not be considered solely an acute event; agencies must be prepared for long-term, potentially chronic ailments, particularly in underserved, rural communities. Efforts to address the long-term health needs of communities post-disaster should consider the perspectives of healthcare providers to offer a well-rounded assessment of community needs. Study findings can help inform future disaster response strategies in communities locally and globally.

Improved spatial learning is associated with increased hippocampal but not prefrontal long-term potentiation in mGluR4 knockout mice.

PubMed

Iscru, E; Goddyn, H; Ahmed, T; Callaerts-Vegh, Z; D'Hooge, R; Balschun, D

2013-08-01

Although much information about metabotropic glutamate receptors (mGluRs) and their role in normal and pathologic brain function has been accumulated during the last decades, the role of group III mGluRs is still scarcely documented. Here, we examined mGluR4 knockout mice for types of behavior and synaptic plasticity that depend on either the hippocampus or the prefrontal cortex (PFC). We found improved spatial short- and long-term memory in the radial arm maze, which was accompanied by enhanced long-term potentiation (LTP) in hippocampal CA1 region. In contrast, LTP in the PFC was unchanged when compared with wild-type controls. Changes in paired-pulse facilitation that became overt in the presence of the GABAA antagonist picrotoxin indicated a function of mGluR4 in maintaining the excitation/inhibition balance, which is of crucial importance for information processing in the brain and the deterioration of these processes in neuropsychological disorders such as autism, epilepsy and schizophrenia. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Long-term bed degradation in Maryland streams (phase 3, part I) : urban streams in the Piedmont Plateau province, [research summary].

DOT National Transportation Integrated Search

2014-09-01

Estimation of potential long-term down-cutting of the stream bed is necessary for evaluation and design of bridges for scour and culverts for fish passage. Existing guidelines for assessing this potential long-term bed degradation (LTBD) in Maryland ...

Long Term TOA - M Data and Information

Atmospheric Science Data Center

2017-09-06

... A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation ... Budget Experiment (ERBE) and Clouds and the Earth's Radiant Energy System (CERES), that span nearly 30 years to date.   The ...

Quality of Life and Functional Health Status of Long-Term Meditators

PubMed Central

Manocha, Ramesh; Black, Deborah; Wilson, Leigh

2012-01-01

Background. There is very little data describing the long-term health impacts of meditation. Aim. To compare the quality of life and functional health of long-term meditators to that of the normative population in Australia. Method. Using the SF-36 questionnaire and a Meditation Lifestyle Survey, we sampled 343 long-term Australian Sahaja Yoga meditation practitioners and compared their scores to those of the normative Australian population. Results. Six SF-36 subscales (bodily pain, general health, mental health, role limitation—emotional, social functioning, and vitality) were significantly better in meditators compared to the national norms whereas two of the subscales (role limitation—physical, physical functioning) were not significantly different. A substantial correlation between frequency of mental silence experience and the vitality, general health, and especially mental health subscales (P < 0.005) was found. Conclusion. Long-term practitioners of Sahaja yoga meditation experience better functional health, especially mental health, compared to the general population. A relationship between functional health, especially mental health, and the frequency of meditative experience (mental silence) exists that may be causal. Evidence for the potential role of this definition of meditation in enhancing quality of life, functional health and wellbeing is growing. Implications for primary mental health prevention are discussed. PMID:22611427

Beyond Quarterly Earnings: Preparing the Business Community for Long-term Climate Risks

NASA Astrophysics Data System (ADS)

Carlson, C.; Goldman, G. T.

2014-12-01

The business community stands to be highly impacted by climate change. In both short and long-term timescales, climate change presents material and financial risks to companies in diverse economic sectors. How the private sector accounts for long-term risks while making short-term decisions about operations is a complex challenge. Companies are accountable to shareholders and must report performance to them on a quarterly basis. At the same time, company investors are exposed to long-term climate-related risks and face losses if companies fail to prepare for climate impacts. The US Securities and Exchange Commission (SEC) obligates publicly traded companies to discuss risks that might materially affect their business and since 2010, the agency recommends that companies consider and discuss any significant risks to their business from climate change. Some companies have complied with this guidance and comprehensively analyze potential climate change impacts, yet others fail to consider climate change at all. Such omissions leave companies without plans for addressing future risks and expose investors and the public to potential catastrophic events from climate change impacts. Climate risk projections can inform companies about the vulnerability of their facilities, supply chains, transportation pathways, and other assets. Such projections can help put climate-related risks in terms of material costs for companies and their investors. Focusing on the vulnerability of coastal facilities, we will use climate change impact projections to demonstrate the economic impacts of climate change faced by the private sector. These risks are then compared to company disclosures to the SEC to assess the degree to which companies have considered their vulnerability to climate change. Finally, we will discuss ways that companies can better assess and manage long-term climate risks.

Long-term biological investigations in space.

PubMed

Lotz, R G; Fuchs, H; Bertsche, U

1975-01-01

Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.

Beyond post-marketing research and MedWatch: Long-term studies of drug risks.

PubMed

Resnik, David B

2007-10-01

Critics of the drug safety system have discussed many different potential reforms, ranging from mandatory registration of clinical trials to increasing the power of regulatory agencies, but few have discussed one of the most important ways of enhancing safety: increasing the number of long-term studies of medications. Long-term studies of the risks and benefits of drugs can provide useful information for regulators, healthcare professionals, and patients. Government funding agencies should lead the effort to conduct long-term studies of drugs, but private companies should also be required to lend financial support. Because cost-effectiveness is likely to be an important consideration in conducting this research, funding agencies should focus, at first, on drugs that are used to treat common, chronic conditions.

Beyond post-marketing research and MedWatch: Long-term studies of drug risks

PubMed Central

Resnik, David B

2007-01-01

Critics of the drug safety system have discussed many different potential reforms, ranging from mandatory registration of clinical trials to increasing the power of regulatory agencies, but few have discussed one of the most important ways of enhancing safety: increasing the number of long-term studies of medications. Long-term studies of the risks and benefits of drugs can provide useful information for regulators, healthcare professionals, and patients. Government funding agencies should lead the effort to conduct long-term studies of drugs, but private companies should also be required to lend financial support. Because cost-effectiveness is likely to be an important consideration in conducting this research, funding agencies should focus, at first, on drugs that are used to treat common, chronic conditions. PMID:19727333

Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease.

PubMed

Monday, Hannah R; Younts, Thomas J; Castillo, Pablo E

2018-04-25

Long-lasting changes of brain function in response to experience rely on diverse forms of activity-dependent synaptic plasticity. Chief among them are long-term potentiation and long-term depression of neurotransmitter release, which are widely expressed by excitatory and inhibitory synapses throughout the central nervous system and can dynamically regulate information flow in neural circuits. This review article explores recent advances in presynaptic long-term plasticity mechanisms and contributions to circuit function. Growing evidence indicates that presynaptic plasticity may involve structural changes, presynaptic protein synthesis, and transsynaptic signaling. Presynaptic long-term plasticity can alter the short-term dynamics of neurotransmitter release, thereby contributing to circuit computations such as novelty detection, modifications of the excitatory/inhibitory balance, and sensory adaptation. In addition, presynaptic long-term plasticity underlies forms of learning and its dysregulation participates in several neuropsychiatric conditions, including schizophrenia, autism, intellectual disabilities, neurodegenerative diseases, and drug abuse. Expected final online publication date for the Annual Review of Neuroscience Volume 41 is July 8, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Embolization of renal angiomyolipomas: short-term and long-term outcomes, complications, and tumor shrinkage.

PubMed

Lee, Shen-Yang; Hsu, Hsiang-Hao; Chen, Yung-Chang; Huang, Chen-Chih; Wong, Yon-Cheong; Wang, Li-Jen; Chuang, Cheng-Keng; Yang, Chih-Wei

2009-11-01

This study retrospectively evaluated outcomes, complications, and tumor shrinkage in renal angiomyolipomas after transcatheter arterial embolization (TAE). All renal angiomyolipoma patients who underwent TAE between August 2000 and December 2008 and had short-term (long-term (>6 months) follow-up images were evaluated. Complications and tumor relapse after TAE were reviewed. The sizes of embolized tumors were measured to calculate size reductions and reduction rates after TAE. Differences in tumor size, size reduction, and reduction rate between different time points (pre-TAE, short-term follow-up, and long-term follow-up) and groups (completely and incompletely embolized) were determined. Eleven renal angiomyolipoma patients who had undergone TAE were included. Seven (63.6%) patients had postembolization syndrome and one had abscess formation following TAE. Two patients had a tumor relapse (18.2%). The mean tumor size was 8.57+/-2.66 cm on pre-TAE images. The mean size reduction was 3.1 cm (33.3%) and 3.8 cm (43.0%) at short-term and long-term follow-up. Tumor sizes differed significantly between pre-TAE and short-term (p=0.004) or long-term images (p=0.022) but not between short-term and long-term images (p=0.059). Results stratified by the completeness of embolization indicate that only the short-term size reduction rate differed significantly (p=0.025), while the long-term reduction rate and short- and long-term follow-up tumor size and size reduction were comparable between the two groups. In conclusion, selective TAE is effective for tumor shrinkage in most renal angiomyolipomas, with acceptable complication and relapse rates. Tumor shrinkage occurring within 6 months after TAE may reflect the long-term effect of TAE.

Sweet Rejuvenation: Linking In-Service and Teacher Induction.

ERIC Educational Resources Information Center

McNair, Veda; And Others

This paper describes a collaborative effort between a local education agency (LEA) and an institution of higher education to link inservice education with induction--teachers teaching teachers. The program, based on the Joyce coaching paradigm and recent cognitive development research, posits that long-term training conducted by trained teachers…

Long-term care legislation: an issue of concern for nurse practitioners.

PubMed

Jennings, J P

1989-01-01

Comprehensive long-term care policy has many hurdles to overcome before it becomes a reality. The biggest hurdle is the price tag! Estimates range from $6 billion (Pepper's home-care bill) to $46 billion (Stark's long-term care coverage bill). Congressional insiders predict that federal long-term care coverage must contain "pay-as-you-go" financing to win congressional passage. The medicare catastrophic health care act is cited by many in the Congress as establishing the precedent for self-financing of new federal benefits. In a pay-as-you-go era in public spending, any new program can only come from trimming existing programs and shifting those funds to new programs or from generating new revenues. The latter could result from increased beneficiary cost-sharing, an increase in the medicare payroll tax, or by eliminating the $45,000 cap on income exposed to the current 1.45% medicare payroll tax. Federal proposals to date build on existing medicare and medicaid programs. In them, quality assurance measures have been strengthened, consumer input encouraged, and a new layer of bureaucracy established to screen potential clients and provide case-management services. The scope of services is broad in most of the current proposals, and reimbursement is provided for respite care to allow family care givers relief and assistance. Access to nurse practitioners' services is an important feature of Kennedy's Lifecare proposal and is the focus of lobbying efforts for all public and private proposals. It is time for nurse practitioners to become involved in long-term care legislation. This may be initiated by reviewing current proposals and long-term care packages offered by major insurance companies. Any future long-term care benefit should bear the imprint of the nurse practitioner's professional perspective and the profession's commitment to humane, caring health policy.

Worldwide impact of aerosol's time scale on the predicted long-term concentrating solar power potential.

PubMed

Ruiz-Arias, Jose A; Gueymard, Christian A; Santos-Alamillos, Francisco J; Pozo-Vázquez, David

2016-08-10

Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

PubMed

Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

2004-03-01

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Two Long-Term Intermittent Pulsars Discovered in the PALFA Survey

NASA Astrophysics Data System (ADS)

Lyne, A. G.; Stappers, B. W.; Freire, P. C. C.; Hessels, J. W. T.; Kaspi, V. M.; Allen, B.; Bogdanov, S.; Brazier, A.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Ferdman, R. D.; Jenet, F. A.; Knispel, B.; Lazarus, P.; van Leeuwen, J.; Lynch, R.; Madsen, E.; McLaughlin, M. A.; Parent, E.; Patel, C.; Ransom, S. M.; Scholz, P.; Seymour, A.; Siemens, X.; Spitler, L. G.; Stairs, I. H.; Stovall, K.; Swiggum, J.; Wharton, R. S.; Zhu, W. W.

2017-01-01

We report the discovery of two long-term intermittent radio pulsars in the ongoing Pulsar Arecibo L-Band Feed Array survey. Following discovery with the Arecibo Telescope, extended observations of these pulsars over several years at Jodrell Bank Observatory have revealed the details of their rotation and radiation properties. PSRs J1910+0517 and J1929+1357 show long-term extreme bimodal intermittency, switching between active (ON) and inactive (OFF) emission states and indicating the presence of a large, hitherto unrecognized underlying population of such objects. For PSR J1929+1357, the initial duty cycle was fON = 0.008, but two years later, this changed quite abruptly to fON = 0.16. This is the first time that a significant evolution in the activity of an intermittent pulsar has been seen, and we show that the spin-down rate of the pulsar is proportional to the activity. The spin-down rate of PSR J1929+1357 is increased by a factor of 1.8 when it is in active mode, similar to the increase seen in the other three known long-term intermittent pulsars. These discoveries increase the number of known pulsars displaying long-term intermittency to five. These five objects display a remarkably narrow range of spin-down power (\\dot{E} ˜ {10}32 {erg} {{{s}}}-1) and accelerating potential above their polar caps. If confirmed by further discoveries, this trend might be important for understanding the physical mechanisms that cause intermittency.

Potential long-term consequences of fad diets on health, cancer, and longevity: lessons learned from model organism studies.

PubMed

Ruden, Douglas M; Rasouli, Parsa; Lu, Xiangyi

2007-06-01

While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people to lose weight purportedly without the severe feelings of deprivation. However, the long-term effects of such fad diets are not known and few experiments have been performed in the laboratory to investigate possible side affects and adverse consequences. In this paper, we review studies with fad-like dietary conditions in humans and model organisms, and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary supplements, and drugs for potential long-term health consequences in model organisms.

Long-Term Engagement in Formal Volunteering and Well-Being: An Exploratory Indian Study

PubMed Central

Elias, Jereesh K.; Sudhir, Paulomi; Mehrotra, Seema

2016-01-01

Sustained engagement in volunteering and its correlates have been examined in many studies across the globe. However, there is a dearth of research that explores the perspectives of long-term formal volunteers on the nature of changes perceived in oneself as a result of volunteering. Moreover, the linkages between psychological well-being and volunteering have been insufficiently explored. The present study was aimed at addressing these gaps. A heterogeneous sample of 20 long-term formal volunteer engaged in volunteering across different voluntary organisations in a southern metropolitan Indian city formed the primary sample for the study. In addition, a group of 21 short-term volunteers, matched on age, income and gender, was utilised for comparison with long-term volunteers on well-being indices. A semi structured interview schedule was used to explore self-perceived changes attributable to volunteering experience. In addition, a few standardised measures were used to comprehensively assess subjective well-being and psychological well-being. The interview data provided rich descriptions of perceived positive changes in self across cognitive, behavioral and emotional domains. Mirroring these patterns, the quantitative analyses indicated that long-term volunteers experienced higher levels of psychological well-being (sense of mastery and competence, self-acceptance and sense of engagement and growth) than short-term volunteers. The potential mechanisms involved in beneficial outcomes of long-term volunteering and implications for further research are highlighted. PMID:27690114

Long-Term Engagement in Formal Volunteering and Well-Being: An Exploratory Indian Study.

PubMed

Elias, Jereesh K; Sudhir, Paulomi; Mehrotra, Seema

2016-09-27

Sustained engagement in volunteering and its correlates have been examined in many studies across the globe. However, there is a dearth of research that explores the perspectives of long-term formal volunteers on the nature of changes perceived in oneself as a result of volunteering. Moreover, the linkages between psychological well-being and volunteering have been insufficiently explored. The present study was aimed at addressing these gaps. A heterogeneous sample of 20 long-term formal volunteer engaged in volunteering across different voluntary organisations in a southern metropolitan Indian city formed the primary sample for the study. In addition, a group of 21 short-term volunteers, matched on age, income and gender, was utilised for comparison with long-term volunteers on well-being indices. A semi structured interview schedule was used to explore self-perceived changes attributable to volunteering experience. In addition, a few standardised measures were used to comprehensively assess subjective well-being and psychological well-being. The interview data provided rich descriptions of perceived positive changes in self across cognitive, behavioral and emotional domains. Mirroring these patterns, the quantitative analyses indicated that long-term volunteers experienced higher levels of psychological well-being (sense of mastery and competence, self-acceptance and sense of engagement and growth) than short-term volunteers. The potential mechanisms involved in beneficial outcomes of long-term volunteering and implications for further research are highlighted.

Potential Use of Deep-ocean Bottom Temperatures Measured by NOAA's Operational DART Systems in Identifying Long-term Climate Trends

NASA Astrophysics Data System (ADS)

Eble, M. C.; Mungov, G.

2016-12-01

The National Oceanic and Atmospheric Administration holds more than 3200 months of ocean bottom temperature time series recorded by the network of Deep-ocean Assessment and Reporting of Tsunami (DART) developed for reporting bottom pressure in support of tsunami detection and warning. Measurements were made at more than 40 locations sited predominately within the Pacific Ocean, with a lesser number made at sites in the North Atlantic. Since 2003, time series data were collected at isolated locations and at those in close proximity to sites measuring other ocean and atmosphere parameters (e.g. TAO/TRITON), at depths ranging from approximately 1800 m to nearly 6000 m. A full 2300 months of temperature measurements were made by DART systems deployed at or below 4000 m. These time series offer the potential of narrowing a gap in the global ocean observing system (OceanObs09) by exposing long-term climate trends at more locations in the ocean deep then now available. The potential held by these data given specific limitations is the focus of this investigation. Limitations stem from the primary function of temperature being to correct pressure. The sole function of temperature has historically been to provide a correction to pressure so little attention has been paid to optimizing temperature measurements for long-term investigations. Temperature counts, like those of pressure, are converted to engineering units using calibration coefficients supplied by the manufacturer but temperatures are only coarsely calibrated. In addition, the response of each pressure transducer to ocean pressure varies by deployment and location. Time series of DART temperature frequency counts recorded during specific single deployments were processed and analyzed to identify consistent trends and explore methodologies that could be adopted in order to improve the utility (NOAA, 2014) of DART temperature measurements for climate studies. These data represent a vast amount of untapped

Vesicular zinc promotes presynaptic and inhibits postsynaptic long term potentiation of mossy fiber-CA3 synapse

PubMed Central

Pan, Enhui; Zhang, Xiao-an; Huang, Zhen; Krezel, Artur; Zhao, Min; Tin-berg, Christine E.; Lippard, Stephen J.; McNamara, James O.

2011-01-01

The presence of zinc in glutamatergic synaptic vesicles of excitatory neurons of mammalian cerebral cortex suggests that zinc might regulate plasticity of synapses formed by these neurons. Long term potentiation (LTP) is a form of synaptic plasticity that may underlie learning and memory. We tested the hypothesis that zinc within vesicles of mossy fibers (mf) contributes to mf-LTP, a classical form of presynaptic LTP. We synthesized an extracellular zinc chelator with selectivity and kinetic properties suitable for study of the large transient of zinc in the synaptic cleft induced by mf stimulation. We found that vesicular zinc is required for presynaptic mf-LTP. Unexpectedly, vesicular zinc also inhibits a novel form of postsynaptic mf-LTP. Because the mf-CA3 synapse provides a major source of excitatory input to the hippocampus, regulating its efficacy by these dual actions of vesicular zinc is critical to proper function of hippocampal circuitry in health and disease. PMID:21943607

Long-term Care Status in Centenarians and Younger Cohorts of Oldest Old in the Last 6 Years of Life: Trajectories and Potential Mechanisms.

PubMed

Gellert, Paul; Eggert, Simon; Zwillich, Christine; Hörter, Stefan; Kuhlmey, Adelheid; Dräger, Dagmar

2018-06-01

A large proportion of the oldest old and centenarians live in long-term care facilities. Although there may be distinct care patterns in centenarians compared with other cohorts of oldest old, the exact development concerning prevalence, length of stay, and factors that are associated with long-term care status in the last years before death is unknown. Longitudinal analyses of health insurance data across 6 years before death. In all, 1398 institutionalized and noninstitutionalized oldest old [deceased at 80-89 (octogenarians), 90-99 (nonagenarians), or over 100 years of age (centenarians)] from Germany were included. Long-term care status and transition from home care into long-term care over 6 years (34,740 person-quarters). Dementia, musculoskeletal diseases, multimorbidity, hospital admission, gender, and age at death were derived from administrative data and analyzed using binary generalized estimating equations. Although the initial level of long-term care (6 years before death) was higher among centenarians (65.1% vs 53.6% in nonagenarians; 36.2% in octogenarians), the rate of increase was stronger in the younger cohorts. Distinguishing between long-term care escapers, delayers, and survivors, the proportion of those who escaped, delayed, or survived the entire 6 years of observation in long-term care was 33.4%/40.4%/26.2% in centenarians, 45.0%/45.1%/9.9% in nonagenarians, and 62.7%/33.7%/3.6% in octogenarians. Age, hospital admissions, and dementia were positively associated with being in long-term care, whereas musculoskeletal disorders were negatively associated with long-term care. The association with dementia was significantly weaker in centenarians. For centenarians, although they are more often in long-term care, the transition rate to long-term care progressed more slowly than the rates of the younger comparison cohorts of oldest old. The high proportion of long stays of centenarians in long-term care facilities require different concepts of

Long-term Water Table Monitoring of Rio Grande Riparian Ecosystems for Restoration Potential Amid Hydroclimatic Challenges.

PubMed

Thibault, James R; Cleverly, James R; Dahm, Clifford N

2017-12-01

Hydrological processes drive the ecological functioning and sustainability of cottonwood-dominated riparian ecosystems in the arid southwestern USA. Snowmelt runoff elevates groundwater levels and inundates floodplains, which promotes cottonwood germination. Once established, these phreatophytes rely on accessible water tables (WTs). In New Mexico's Middle Rio Grande corridor diminished flooding and deepening WTs threaten native riparian communities. We monitored surface flows and riparian WTs for up to 14 years, which revealed that WTs and surface flows, including peak snowmelt discharge, respond to basin climate conditions and resource management. WT hydrographs influence the composition of riparian communities and can be used to assess if potential restoration sites meet native vegetation tolerances for WT depths, rates of recession, and variability throughout their life stages. WTs were highly variable in some sites, which can preclude native vegetation less adapted to deep drawdowns during extended droughts. Rates of WT recession varied between sites and should be assessed in regard to recruitment potential. Locations with relatively shallow WTs and limited variability are likely to be more viable for successful restoration. Suitable sites have diminished greatly as the once meandering Rio Grande has been constrained and depleted. Increasing demands on water and the presence of invasive vegetation better adapted to the altered hydrologic regime further impact native riparian communities. Long-term monitoring over a range of sites and hydroclimatic extremes reveals attributes that can be evaluated for restoration potential.

Long-term Water Table Monitoring of Rio Grande Riparian Ecosystems for Restoration Potential Amid Hydroclimatic Challenges

NASA Astrophysics Data System (ADS)

Thibault, James R.; Cleverly, James R.; Dahm, Clifford N.

2017-12-01

Hydrological processes drive the ecological functioning and sustainability of cottonwood-dominated riparian ecosystems in the arid southwestern USA. Snowmelt runoff elevates groundwater levels and inundates floodplains, which promotes cottonwood germination. Once established, these phreatophytes rely on accessible water tables (WTs). In New Mexico's Middle Rio Grande corridor diminished flooding and deepening WTs threaten native riparian communities. We monitored surface flows and riparian WTs for up to 14 years, which revealed that WTs and surface flows, including peak snowmelt discharge, respond to basin climate conditions and resource management. WT hydrographs influence the composition of riparian communities and can be used to assess if potential restoration sites meet native vegetation tolerances for WT depths, rates of recession, and variability throughout their life stages. WTs were highly variable in some sites, which can preclude native vegetation less adapted to deep drawdowns during extended droughts. Rates of WT recession varied between sites and should be assessed in regard to recruitment potential. Locations with relatively shallow WTs and limited variability are likely to be more viable for successful restoration. Suitable sites have diminished greatly as the once meandering Rio Grande has been constrained and depleted. Increasing demands on water and the presence of invasive vegetation better adapted to the altered hydrologic regime further impact native riparian communities. Long-term monitoring over a range of sites and hydroclimatic extremes reveals attributes that can be evaluated for restoration potential.

Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression.

PubMed Central

Molinari, S; Battini, R; Ferrari, S; Pozzi, L; Killcross, A S; Robbins, T W; Jouvenceau, A; Billard, J M; Dutar, P; Lamour, Y; Baker, W A; Cox, H; Emson, P C

1996-01-01

The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function. Images Fig. 1 PMID:8755597

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

PubMed

Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

2015-10-01

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats.

PubMed

Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

2014-09-02

Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle-box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus. Copyright

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

... December 29, 2007, was co-located with an entity that is a provider-based, off-campus location of a... hospital or the satellite facility from any individual hospital not co-located with the long-term care... from any individual hospital not co-located with the long-term care hospital or with the satellite of a...

Long-term functioning following whiplash injury: the role of social support and personality traits.

PubMed

Nijs, Jo; Inghelbrecht, Els; Daenen, Liesbeth; Hachimi-Idrissi, Said; Hens, Luc; Willems, Bert; Roussel, Nathalie; Cras, Patrick; Bernheim, Jan

2011-07-01

Transition from acute whiplash injury to either recovery or chronicity and the development of chronic whiplash-associated disorders (WAD) remains a challenging issue for researchers and clinicians. The roles of social support and personality traits in long-term functioning following whiplash have not been studied concomitantly. The present study aimed to examine whether social support and personality traits are related to long-term functioning following whiplash. One hundred forty-three subjects, who had experienced a whiplash injury in a traffic accident 10-26 months before the study took place, participated. The initial diagnoses were a 'sprain of the neck' (ICD-9 code 847.0); only the outcome of grades I-III acute WAD was studied. Long-term functioning was considered within the biopsychosocial model: it was expressed in terms of disability, functional status, quality of life and psychological well-being. Participants filled out a set of questionnaires to measure the long-term functioning parameters (i.e. the Neck Disability Index, Medical Outcome Study Short-Form General Health Survey, Anamnestic Comparative Self-Assessment measure of overall well-being and the Symptom Checklist-90) and potential determinants of long-term functioning (the Dutch Personality Questionnaire and the Social Support List). The results suggest that social support (especially the discrepancies dimension of social support) and personality traits (i.e. inadequacy, self-satisfaction and resentment) are related to long-term functioning following whiplash injury (Spearman rho varied between 0.32 and 0.57; p < 0.01). Within the discrepancy dimension, everyday emotional support, emotional support during problems, appreciative support and informative support were identified as important correlates of long-term functioning. Future prospective studies are required to confirm the role of social support and personality traits in relation to long-term functioning following whiplash. For such

DO HERBAL AGENTS HAVE A PLACE IN THE TREATMENT OF SLEEP PROBLEMS IN LONG-TERM CARE?

PubMed Central

Shimazaki, Mark; Martin, Jennifer L.

2007-01-01

Sleep disruption is common in the long-term care setting. This paper discusses the available literature on two herbal approaches to sleep problems in long-term care. The largest body of evidence exists for the use of the dietary/herbal supplements valerian and melatonin. While these agents appear to have a modest positive effect on sleep quality among older adults, most studies were small in size and included only subjective assessments of sleep quality. In addition, it is unclear whether these agents pose risks to long-term care residents due to potential drug interactions. Additional research is needed prior to making conclusive recommendations about the use of these interventions for sleep in the long-term care setting. PMID:17498609

Short-term and long-term treatment outcomes with Class III activator

PubMed Central

Ryu, Hyo-kyung; Chong, Hyun-Jeong; An, Ki-Yong

2015-01-01

Objective The purpose of this retrospective study was to investigate short-term and long-term skeletodental outcomes of Class III activator treatment. Methods A Class III activator treatment group (AG) comprised of 22 patients (9 boys, 13 girls) was compared with a Class III control group (CG) comprised of 17 patients (6 boys, 11 girls). The total treatment period was divided into three stages; the initial stage (T1), the post-activator treatment or post-mandibular growth peak stage (T2), and the long-term follow-up stage (T3). Cephalometric changes were evaluated statistically via the Mann-Whitney U-test and the Friedman test. Results The AG exhibited significant increases in the SNA angle, ANB angle, Wits appraisal, A point-N perpendicular, Convexity of A point, and proclination of the maxillary incisors, from T1 to T2. In the long-term follow-up (T1-T3), the AG exhibited significantly greater increases in the ANB angle, Wits appraisal, and Convexity of A point than the CG. Conclusions Favorable skeletal outcomes induced during the Class III activator treatment period were generally maintained until the long-term follow-up period of the post-mandibular growth peak stage. PMID:26445717

[Psychosocial issues of long-term cancer survivors].

PubMed

Weis, J; Faller, H

2012-04-01

Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

A security/safety survey of long term care facilities.

PubMed

Acorn, Jonathan R

2010-01-01

What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

PubMed Central

Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

2016-01-01

Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin–mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

Effects of grasp compatibility on long-term memory for objects.

PubMed

Canits, Ivonne; Pecher, Diane; Zeelenberg, René

2018-01-01

Previous studies have shown action potentiation during conceptual processing of manipulable objects. In four experiments, we investigated whether these motor actions also play a role in long-term memory. Participants categorized objects that afforded either a power grasp or a precision grasp as natural or artifact by grasping cylinders with either a power grasp or a precision grasp. In all experiments, responses were faster when the affordance of the object was compatible with the type of grasp response. However, subsequent free recall and recognition memory tasks revealed no better memory for object pictures and object names for which the grasp affordance was compatible with the grasp response. The present results therefore do not support the hypothesis that motor actions play a role in long-term memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Islet Transplantation in Type 1 Diabetes: Ongoing Challenges, Refined Procedures, and Long-Term Outcome

PubMed Central

Shapiro, A.M. James

2012-01-01

Remarkable progress has been made in islet transplantation over a span of 40 years. Once just an experimental curiosity in mice, this therapy has moved forward, and can now provide robust therapy for highly selected patients with type 1 diabetes (T1D), refractory to stabilization by other means. This progress could not have occurred without extensive dynamic international collaboration. Currently, 1,085 patients have undergone islet transplantation at 40 international sites since the Edmonton Protocol was reported in 2000 (752 allografts, 333 autografts), according to the Collaborative Islet Transplant Registry. The long-term results of islet transplantation in selected centers now match registry data of pancreas-alone transplantation, with 6 sites reporting five-year insulin independence rates ≥50%. Islet transplantation has been criticized for the use of multiple donor pancreas organs, but progress has also occurred in single-donor success, with 10 sites reporting increased single-donor engraftment. The next wave of innovative clinical trial interventions will address instant blood-mediated inflammatory reaction (IBMIR), apoptosis, and inflammation, and will translate into further marked improvements in single-donor success. Effective control of auto- and alloimmunity is the key to long-term islet function, and high-resolution cellular and antibody-based assays will add considerable precision to this process. Advances in immunosuppression, with new antibody-based targeting of costimulatory blockade and other T-B cellular signaling, will have further profound impact on the safety record of immunotherapy. Clinical trials will move forward shortly to test out new human stem cell derived islets, and in parallel trials will move forward, testing pig islets for compatibility in patients. Induction of immunological tolerance to self-islet antigens and to allografts is a difficult challenge, but potentially within our grasp. PMID:23804275

Serum aminoacylase-1 is a novel biomarker with potential prognostic utility for long-term outcome in patients with delayed graft function following renal transplantation

PubMed Central

Welberry Smith, Matthew P; Zougman, Alexandre; Cairns, David A; Wilson, Michelle; Wind, Tobias; Wood, Steven L; Thompson, Douglas; Messenger, Michael P; Mooney, Andrew; Selby, Peter J; Lewington, Andrew J P; Banks, Rosamonde E

2013-01-01

Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67–0.85) for ACY-1, 0.9 (0.84–0.95) for cystatin C, and 0.93 (0.88–0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor–brain–dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation. PMID:23739232

Long-Term Planetary Habitability and the Carbonate-Silicate Cycle

NASA Astrophysics Data System (ADS)

Rushby, Andrew J.; Johnson, Martin; Mills, Benjamin J. W.; Watson, Andrew J.; Claire, Mark W.

2018-05-01

The potential habitability of an exoplanet is traditionally assessed by determining if its orbit falls within the circumstellar `habitable zone' of its star, defined as the distance at which water could be liquid on the surface of a planet (Kopparapu et al., 2013). Traditionally, these limits are determined by radiative-convective climate models, which are used to predict surface temperatures at user-specified levels of greenhouse gases. This approach ignores the vital question of the (bio)geochemical plausibility of the proposed chemical abundances. Carbon dioxide is the most important greenhouse gas in Earth's atmosphere in terms of regulating planetary temperature, with the long term concentration controlled by the balance between volcanic outgassing and the sequestration of CO2 via chemical weathering and sedimentation, as modulated by ocean chemistry, circulation and biological (microbial) productivity. We develop a model incorporating key aspects of Earth's short and long-term biogeochemical carbon cycle to explore the potential changes in the CO2 greenhouse due to variance in planet size and stellar insolation. We find that proposed changes in global topography, tectonics, and the hydrological cycle on larger planets results in proportionally greater surface temperatures for a given incident flux. For planets between 0.5 to 2 R_earth the effect of these changes results in average global surface temperature deviations of up to 20 K, which suggests that these relationships must be considered in future studies of planetary habitability.