Science.gov

Sample records for long-lasting intrinsic plasticity

  1. In search of general mechanisms for long-lasting plasticity: Aplysia and the hippocampus.

    PubMed Central

    Pittenger, Christopher; Kandel, Eric R

    2003-01-01

    Long-term synaptic plasticity is thought to underlie many forms of long-lasting memory. Long-lasting plasticity has been most extensively studied in the marine snail Aplysia and in the mammalian hippocampus, where Bliss and Lømo first described long-term potentiation 30 years ago. The molecular mechanisms of plasticity in these two systems have proven to have many similarities. Here, we briefly describe some of these areas of overlap. We then summarize recent advances in our understanding of the mechanisms of long-lasting synaptic facilitation in Aplysia and suggest that these may prove fruitful areas for future investigation in the mammalian hippocampus and at other synapses in the mammalian brain. PMID:12740123

  2. Long-lasting reconfiguration of two interacting networks by a cooperation of presynaptic and postsynaptic plasticity.

    PubMed

    Nargeot, R

    2001-05-01

    The functional reconfiguration of central neuronal networks, a phenomenon by which neurons change their participation in network operation, is important for organizing adaptive behaviors. Such reconfiguration can be expressed in a long-lasting manner (hours, days) after a training paradigm. The present study shows that such a long-lasting network reconfiguration requires a cooperation of both presynaptic and postsynaptic modifications in a neuronal interaction between two functionally distinct networks. In isolated preparations of the lobster stomatogastric nervous system, the single ventral dilator (VD) neuron can switch its functional participation from one discrete network (the pyloric network) to another (the cardiac sac network). This switching capability can be long-lasting and can be induced by a sensitizing procedure. A persistent change that was associated with this neuronal switching was found in each of the two networks. First, the intrinsic membrane properties of the VD neuron that allow it to participate spontaneously in the pyloric network are altered. Second, bursting activity is strengthened in the inferior ventricular neurons that both drive cardiac sac network activity and monosynaptically excite the VD neuron in phase with this network activity. Importantly, these changes in intrinsic properties of both presynaptic and postsynaptic neurons are required to allow the VD neuron switching, because expression of either the presynaptic or the postsynaptic change alone did not permit VD neuron switching to occur. These results suggest that a cooperative modification of a discrete network interaction is able to persistently switch the output pattern of a motor neuron as a result of a sensitizing paradigm.

  3. Long-lasting modification of intrinsic discharge properties in subicular neurons following status epilepticus.

    PubMed

    Wellmer, Jörg; Su, Hailing; Beck, Heinz; Yaari, Yoel

    2002-07-01

    A single episode of status epilepticus (SE) induces neuropathological changes in the brain that may lead to the development of a permanent epileptic condition. Most studies of this plasticity have focused on the hippocampus, where both synaptic function and intrinsic neuronal excitability have been shown to be persistently modified by SE. However, many other brain structures are activated during SE and may also be involved in the subsequent epileptogenic process. Here we have investigated whether SE, induced in rats with pilocarpine and terminated after 40 min with diazepam, persistently modifies the intrinsic excitability of pyramidal neurons in the subiculum. Subicular slices were prepared from control and SE-experienced rats (2-5 weeks after SE). In the control group, only 4% of the neurons fired bursts in response to intrasomatic, threshold-straddling depolarizing current pulses (low-threshold bursters). The remaining neurons either fired bursts in response to strong (3x threshold) depolarizations (35%; high-threshold bursters) or fired in a completely regular mode (61%; nonbursters). In the SE-experienced group, the fractions of low- and high-threshold bursters markedly increased to 29% and 53%, respectively. This change in firing behaviour was associated with a marked increase in the size of the spike after depolarization, particularly in low-threshold bursters. Experimental suppression of Ca2+ currents selectively blocked low-threshold bursting but did not affect high-threshold bursting, suggesting that a dual Ca2+- dependent and Ca2+- independent mechanism controls bursting in these neurons. The persistent up-regulation of intrinsic bursting in the subiculum, in concert with similar changes in the hippocampus, undoubtedly contributes to epileptogenesis following pilocarpine-induced SE.

  4. An Early Sensitive Period Induces Long-Lasting Plasticity in the Honeybee Nervous System.

    PubMed

    Grosso, Juan P; Barneto, Jesica A; Velarde, Rodrigo A; Pagano, Eduardo A; Zavala, Jorge A; Farina, Walter M

    2018-01-01

    The effect of early experiences on the brain during a sensitive period exerts a long-lasting influence on the mature individual. Despite behavioral and neural plasticity caused by early experiences having been reported in the honeybee Apis mellifera , the presence of a sensitive period in which associative experiences lead to pronounced modifications in the adult nervous system is still unclear. Laboratory-reared bees were fed with scented food within specific temporal windows and were assessed for memory retention, in the regulation of gene expression related to the synaptic formation and in the olfactory perception of their antennae at 17 days of age. Bees were able to retain a food-odor association acquired 5-8 days after emergence, but not before, and showed better retention than those exposed to an odor at 9-12 days. In the brain, the odor-rewarded experiences that occurred at 5-8 days of age boosted the expression levels of the cell adhesion proteins neurexin 1 ( Nrx1 ) and neuroligin 2 ( Nlg2 ) involved in synaptic strength. At the antennae, the experiences increased the electrical response to a novel odor but not to the one experienced. Therefore, a sensitive period that induces long-lasting behavioral, functional and structural changes is found in adult honeybees.

  5. An Early Sensitive Period Induces Long-Lasting Plasticity in the Honeybee Nervous System

    PubMed Central

    Grosso, Juan P.; Barneto, Jesica A.; Velarde, Rodrigo A.; Pagano, Eduardo A.; Zavala, Jorge A.; Farina, Walter M.

    2018-01-01

    The effect of early experiences on the brain during a sensitive period exerts a long-lasting influence on the mature individual. Despite behavioral and neural plasticity caused by early experiences having been reported in the honeybee Apis mellifera, the presence of a sensitive period in which associative experiences lead to pronounced modifications in the adult nervous system is still unclear. Laboratory-reared bees were fed with scented food within specific temporal windows and were assessed for memory retention, in the regulation of gene expression related to the synaptic formation and in the olfactory perception of their antennae at 17 days of age. Bees were able to retain a food-odor association acquired 5–8 days after emergence, but not before, and showed better retention than those exposed to an odor at 9–12 days. In the brain, the odor-rewarded experiences that occurred at 5–8 days of age boosted the expression levels of the cell adhesion proteins neurexin 1 (Nrx1) and neuroligin 2 (Nlg2) involved in synaptic strength. At the antennae, the experiences increased the electrical response to a novel odor but not to the one experienced. Therefore, a sensitive period that induces long-lasting behavioral, functional and structural changes is found in adult honeybees. PMID:29449804

  6. Translating innate response into long-lasting antibody response by the intrinsic antigen-adjuvant properties of papaya mosaic virus

    PubMed Central

    Acosta-Ramírez, Elizabeth; Pérez-Flores, Rebeca; Majeau, Nathalie; Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Ramírez-Saldaña, Maricela; Manjarrez-Orduño, Nataly; Cervantes-Barragán, Luisa; Santos-Argumedo, Leopoldo; Flores-Romo, Leopoldo; Becker, Ingeborg; Isibasi, Armando; Leclerc, Denis; López-Macías, Constantino

    2008-01-01

    Identifying the properties of a molecule involved in the efficient activation of the innate and adaptive immune responses that lead to long-lasting immunity is crucial for vaccine and adjuvant development. Here we show that the papaya mosaic virus (PapMV) is recognized by the immune system as a pathogen-associated molecular pattern (PAMP) and as an antigen in mice (Pamptigen). A single immunization of PapMV without added adjuvant efficiently induced both cellular and specific long-lasting antibody responses. PapMV also efficiently activated innate immune responses, as shown by the induction of lipid raft aggregation, secretion of pro-inflammatory cytokines, up-regulation of co-stimulatory molecules on dendritic cells and macrophages, and long-lasting adjuvant effects upon the specific antibody responses to model antigens. PapMV mixed with Salmonella enterica serovar Typhi (S. typhi) outer membrane protein C increased its protective capacity against challenge with S. typhi, revealing the intrinsic adjuvant properties of PapMV in the induction of immunity. Antigen-presenting cells loaded with PapMV efficiently induced antibody responses in vivo, which may link the innate and adaptive responses observed. PapMV recognition as a Pamptigen might be translated into long-lasting antibody responses and protection observed. These properties could be used in the development of new vaccine platforms. PMID:18070030

  7. Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

    PubMed

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

    2014-01-01

    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. 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 has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we 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. © 2014 Elsevier Inc. All rights reserved.

  8. Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO2 responsiveness to overcome dysfunction

    NASA Astrophysics Data System (ADS)

    Mosher, Bryan Patrick

    The ability of the brain to detect (central CO2 chemosensitivity) and respond to (central CO2 chemoresponsiveness) changes in tissue CO2/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilatory CO 2 chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe contributions to central chemosensitivity involving both 5-HT- and gamma-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO2) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO2 responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO2 responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO2 responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO2 responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO2 responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc--induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into

  9. Functional MRI neurofeedback training on connectivity between two regions induces long-lasting changes in intrinsic functional network

    PubMed Central

    Megumi, Fukuda; Yamashita, Ayumu; Kawato, Mitsuo; Imamizu, Hiroshi

    2015-01-01

    Motor or perceptual learning is known to influence functional connectivity between brain regions and induce short-term changes in the intrinsic functional networks revealed as correlations in slow blood-oxygen-level dependent (BOLD) signal fluctuations. However, no cause-and-effect relationship has been elucidated between a specific change in connectivity and a long-term change in global networks. Here, we examine the hypothesis that functional connectivity (i.e., temporal correlation between two regions) is increased and preserved for a long time when two regions are simultaneously activated or deactivated. Using the connectivity-neurofeedback training paradigm, subjects successfully learned to increase the correlation of activity between the lateral parietal and primary motor areas, regions that belong to different intrinsic networks and negatively correlated before training under the resting conditions. Furthermore, whole-brain hypothesis-free analysis as well as functional network analyses demonstrated that the correlation in the resting state between these areas as well as the correlation between the intrinsic networks that include the areas increased for at least 2 months. These findings indicate that the connectivity-neurofeedback training can cause long-term changes in intrinsic connectivity and that intrinsic networks can be shaped by experience-driven modulation of regional correlation. PMID:25870552

  10. Long-lasting intrinsic persistent firing in rat CA1 pyramidal cells: a possible mechanism for active maintenance of memory.

    PubMed

    Knauer, Beate; Jochems, Arthur; Valero-Aracama, Maria Jesus; Yoshida, Motoharu

    2013-09-01

    The hippocampus is critical for memory tasks which require an active maintenance of memory for a short period of time; however, the underlying neural mechanisms remain unknown. Most theoretical and computational models, which date back to the classic proposals by Donald Hebb in , have been self-constrained by anatomy, as most models rely on the recurrent connectivity in region CA3 to support "reverberating activity" capable of memory maintenance. However, several physiological and behavioral studies have specifically implicated region CA1 in tasks which require an active maintenance of memory. Here, we demonstrate that despite limited recurrent connectivity, CA1 contains a robust cellular mechanism for active memory maintenance in the form of self-sustained persistent firing. Using in vitro whole-cell recordings, we demonstrate that brief stimulation (0.2-2 s) reliably elicits long-lasting (> 30 s) persistent firing that is supported by the calcium-activated non-selective cationic current. In contrast to more traditional ideas, these data suggest that the hippocampal region CA1 is capable of active maintenance of memory. Copyright © 2013 Wiley Periodicals, Inc.

  11. Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity

    PubMed Central

    Dixon, Luke; Santora, Danielle; Ibrahim, Mohamed M.

    2015-01-01

    Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans. PMID:26108955

  12. Long-lasting changes in hippocampal synaptic plasticity and cognition in an animal model of NMDA receptor dysfunction in psychosis.

    PubMed

    Wiescholleck, Valentina; Manahan-Vaughan, Denise

    2013-11-01

    It is postulated that disruptions of glutamatergic signalling may underlie the pathophysiology of psychosis and schizophrenia. A strong body of evidence indicates that antagonism of the N-methyl-d-aspartate receptor (NMDAR) leads to similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans to those that have been identified to occur in psychosis. One of the main loci of change appears to comprise the hippocampus, raising the question as to whether changes in hippocampal glutamatergic transmission may drive changes in GABAergic and dopaminergic-mediated signalling in schizophreniform diseases. NMDAR antagonists such as MK801, PCP and ketamine all elicit similar psychosis-related effects, with MK801 inducing the most potent psychotomimetic reactions. Treatment with MK801 is associated with a loss of hippocampal synaptic plasticity, hippocampus-dependent learning and cognitive deficits. These findings have raised the question as to whether targeting the NMDA receptors or its modulators could prove an effective strategy in treatment of psychosis and schizophrenia. Specifically, the otherwise untreatable negative and cognitive symptoms of schizophrenia currently comprise the highest research priority. A single injection with MK801 has been used to emulate first-episode psychosis in animals. This treatment induces both psychosis-related acute effects but interestingly also persisting consequences, which might be more sensitive as indicators of drug efficacy. Here, we review the current status of the field with regard to the MK801 animal model of first-episode psychosis and its relevance for the glutamate hypothesis of schizophrenia. Furthermore, we argue that synaptic plasticity may be a better assay for assessing novel schizophrenia therapeutics than behavioural evaluation. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Towards long lasting zirconia-based composites for dental implants: Transformation induced plasticity and its consequence on ceramic reliability.

    PubMed

    Reveron, Helen; Fornabaio, Marta; Palmero, Paola; Fürderer, Tobias; Adolfsson, Erik; Lughi, Vanni; Bonifacio, Alois; Sergo, Valter; Montanaro, Laura; Chevalier, Jérôme

    2017-01-15

    Zirconia-based composites were developed through an innovative processing route able to tune compositional and microstructural features very precisely. Fully-dense ceria-stabilized zirconia ceramics (84vol% Ce-TZP) containing equiaxed alumina (8vol%Al 2 O 3 ) and elongated strontium hexa-aluminate (8vol% SrAl 12 O 19 ) second phases were obtained by conventional sintering. This work deals with the effect of the zirconia stabilization degree (CeO 2 in the range 10.0-11.5mol%) on the transformability and mechanical properties of Ce-TZP-Al 2 O 3 -SrAl 12 O 19 materials. Vickers hardness, biaxial flexural strength and Single-edge V-notched beam tests revealed a strong influence of ceria content on the mechanical properties. Composites with 11.0mol% CeO 2 or above exhibited the classical behaviour of brittle ceramics, with no apparent plasticity and very low strain to failure. On the contrary, composites with 10.5mol% CeO 2 or less showed large transformation-induced plasticity and almost no dispersion in strength data. Materials with 10.5mol% of ceria showed the highest values in terms of biaxial bending strength (up to 1.1GPa) and fracture toughness (>10MPa√m). In these ceramics, as zirconia transformation precedes failure, the Weibull modulus was exceptionally high and reached a value of 60, which is in the range typically reported for metals. The results achieved demonstrate the high potential of using these new strong, tough and stable zirconia-based composites in structural biomedical applications. Yttria-stabilized (Y-TZP) zirconia ceramics are increasingly used for developing metal-free restorations and dental implants. Despite their success related to their excellent mechanical resistance, Y-TZP can undergo Low Temperature Degradation which could be responsible for restoration damage or even worst the failure of the implant. Current research is focusing on strategies to improve the LTD resistance of Y-TZP or to develop alternative composites with better

  14. Spike-Timing Dependent Plasticity Beyond Synapse – Pre- and Post-Synaptic Plasticity of Intrinsic Neuronal Excitability

    PubMed Central

    Debanne, Dominique; Poo, Mu-Ming

    2010-01-01

    Long-lasting plasticity of synaptic transmission is classically thought to be the cellular substrate for information storage in the brain. Recent data indicate however that it is not the whole story and persistent changes in the intrinsic neuronal excitability have been shown to occur in parallel to the induction of long-term synaptic modifications. This form of plasticity depends on the regulation of voltage-gated ion channels. Here we review the experimental evidence for plasticity of neuronal excitability induced at pre- or postsynaptic sites when long-term plasticity of synaptic transmission is induced with Spike-Timing Dependent Plasticity (STDP) protocols. We describe the induction and expression mechanisms of the induced changes in excitability. Finally, the functional synergy between synaptic and non-synaptic plasticity and their spatial extent are discussed. PMID:21423507

  15. Spike-timing dependent plasticity beyond synapse - pre- and post-synaptic plasticity of intrinsic neuronal excitability.

    PubMed

    Debanne, Dominique; Poo, Mu-Ming

    2010-01-01

    Long-lasting plasticity of synaptic transmission is classically thought to be the cellular substrate for information storage in the brain. Recent data indicate however that it is not the whole story and persistent changes in the intrinsic neuronal excitability have been shown to occur in parallel to the induction of long-term synaptic modifications. This form of plasticity depends on the regulation of voltage-gated ion channels. Here we review the experimental evidence for plasticity of neuronal excitability induced at pre- or postsynaptic sites when long-term plasticity of synaptic transmission is induced with Spike-Timing Dependent Plasticity (STDP) protocols. We describe the induction and expression mechanisms of the induced changes in excitability. Finally, the functional synergy between synaptic and non-synaptic plasticity and their spatial extent are discussed.

  16. Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

    PubMed Central

    He, Guiqin; Yang, Xiangyu; Wang, Guo; Qi, Junxia; Mao, Rui; Wu, Zhengping; Zhou, Zikai

    2017-01-01

    In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs) remains unclear. Cyclin-dependent kinases (Cdks) are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH) and the only known Cdk-activating kinase (CAK) in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS) and prevented the formation of long-term memories. PMID:29163040

  17. Long lasting decontamination foam

    DOEpatents

    Demmer, Ricky L.; Peterman, Dean R.; Tripp, Julia L.; Cooper, David C.; Wright, Karen E.

    2010-12-07

    Compositions and methods for decontaminating surfaces are disclosed. More specifically, compositions and methods for decontamination using a composition capable of generating a long lasting foam are disclosed. Compositions may include a surfactant and gelatin and have a pH of less than about 6. Such compositions may further include affinity-shifting chemicals. Methods may include decontaminating a contaminated surface with a composition or a foam that may include a surfactant and gelatin and have a pH of less than about 6.

  18. IGFBP2 Produces Rapid-Acting and Long-Lasting Effects in Rat Models of Posttraumatic Stress Disorder via a Novel Mechanism Associated with Structural Plasticity

    PubMed Central

    Colechio, Elizabeth M.; Ghoreishi-Haack, Nayereh; Gross, Amanda L.; Rex, Christopher S.; Zhang, Xiao-lei; Stanton, Patric K.; Kroes, Roger A.; Moskal, Joseph R.

    2017-01-01

    Abstract Background: Posttraumatic stress disorder is an anxiety disorder characterized by deficits in the extinction of aversive memories. Insulin-like growth factor 1 (IGF1) is the only growth factor that has shown anxiolytic and antidepressant properties in human clinical trials. In animal studies, insulin-like growth factor binding protein 2 (IGFBP2) shows both IGF1-dependent and IGF1-independent pharmacological effects, and IGFBP2 expression is upregulated by rough-and-tumble play that induces resilience to stress. Methods: IGFBP2 was evaluated in Porsolt, contextual fear conditioning, and chronic unpredictable stress models of posttraumatic stress disorder. The dependence of IGFBP2 effects on IGF1- and AMPA-receptor activation was tested using selective receptor antagonists. Dendritic spine morphology was measured in the dentate gyrus and the medial prefrontal cortex 24 hours after in vivo dosing. Results: IGFBP2 was 100 times more potent than IGF1 in the Porsolt test. Unlike IGF1, effects of IGFBP2 were not blocked by the IGF1-receptor antagonist JB1, or by the AMPA-receptor antagonist 2,3-Dioxo-6-nitro-1,2,3,4 tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) in the Porsolt test. IGFBP2 (1 µg/kg) and IGF1 (100 µg/kg i.v.) each facilitated contextual fear extinction and consolidation. Using a chronic unpredictable stress paradigm, IGFBP2 reversed stress-induced effects in the Porsolt, novelty-induced hypophagia, sucrose preference, and ultrasonic vocalization assays. IGFBP2 also increased mature dendritic spine densities in the medial prefrontal cortex and hippocampus 24 hours postdosing. Conclusions: These data suggest that IGFBP2 has therapeutic-like effects in multiple rat models of posttraumatic stress disorder via a novel IGF1 receptor-independent mechanism. These data also suggest that the long-lasting effects of IGFBP2 may be due to facilitation of structural plasticity at the dendritic spine level. IGFBP2 and mimetics may have therapeutic

  19. IGFBP2 Produces Rapid-Acting and Long-Lasting Effects in Rat Models of Posttraumatic Stress Disorder via a Novel Mechanism Associated with Structural Plasticity.

    PubMed

    Burgdorf, Jeffrey; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda L; Rex, Christopher S; Zhang, Xiao-Lei; Stanton, Patric K; Kroes, Roger A; Moskal, Joseph R

    2017-06-01

    Posttraumatic stress disorder is an anxiety disorder characterized by deficits in the extinction of aversive memories. Insulin-like growth factor 1 (IGF1) is the only growth factor that has shown anxiolytic and antidepressant properties in human clinical trials. In animal studies, insulin-like growth factor binding protein 2 (IGFBP2) shows both IGF1-dependent and IGF1-independent pharmacological effects, and IGFBP2 expression is upregulated by rough-and-tumble play that induces resilience to stress. IGFBP2 was evaluated in Porsolt, contextual fear conditioning, and chronic unpredictable stress models of posttraumatic stress disorder. The dependence of IGFBP2 effects on IGF1- and AMPA-receptor activation was tested using selective receptor antagonists. Dendritic spine morphology was measured in the dentate gyrus and the medial prefrontal cortex 24 hours after in vivo dosing. IGFBP2 was 100 times more potent than IGF1 in the Porsolt test. Unlike IGF1, effects of IGFBP2 were not blocked by the IGF1-receptor antagonist JB1, or by the AMPA-receptor antagonist 2,3-Dioxo-6-nitro-1,2,3,4 tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) in the Porsolt test. IGFBP2 (1 µg/kg) and IGF1 (100 µg/kg i.v.) each facilitated contextual fear extinction and consolidation. Using a chronic unpredictable stress paradigm, IGFBP2 reversed stress-induced effects in the Porsolt, novelty-induced hypophagia, sucrose preference, and ultrasonic vocalization assays. IGFBP2 also increased mature dendritic spine densities in the medial prefrontal cortex and hippocampus 24 hours postdosing. These data suggest that IGFBP2 has therapeutic-like effects in multiple rat models of posttraumatic stress disorder via a novel IGF1 receptor-independent mechanism. These data also suggest that the long-lasting effects of IGFBP2 may be due to facilitation of structural plasticity at the dendritic spine level. IGFBP2 and mimetics may have therapeutic potential for the treatment of posttraumatic stress disorder.

  20. Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity

    NASA Astrophysics Data System (ADS)

    Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2013-11-01

    The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long-term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75NTR pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75NTR pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75NTR-masking conditions, thus supporting the aforementioned hypothesis.

  1. Dynamic Neural Fields with Intrinsic Plasticity

    PubMed Central

    Strub, Claudius; Schöner, Gregor; Wörgötter, Florentin; Sandamirskaya, Yulia

    2017-01-01

    Dynamic neural fields (DNFs) are dynamical systems models that approximate the activity of large, homogeneous, and recurrently connected neural networks based on a mean field approach. Within dynamic field theory, the DNFs have been used as building blocks in architectures to model sensorimotor embedding of cognitive processes. Typically, the parameters of a DNF in an architecture are manually tuned in order to achieve a specific dynamic behavior (e.g., decision making, selection, or working memory) for a given input pattern. This manual parameters search requires expert knowledge and time to find and verify a suited set of parameters. The DNF parametrization may be particular challenging if the input distribution is not known in advance, e.g., when processing sensory information. In this paper, we propose the autonomous adaptation of the DNF resting level and gain by a learning mechanism of intrinsic plasticity (IP). To enable this adaptation, an input and output measure for the DNF are introduced, together with a hyper parameter to define the desired output distribution. The online adaptation by IP gives the possibility to pre-define the DNF output statistics without knowledge of the input distribution and thus, also to compensate for changes in it. The capabilities and limitations of this approach are evaluated in a number of experiments. PMID:28912706

  2. Dynamic Neural Fields with Intrinsic Plasticity.

    PubMed

    Strub, Claudius; Schöner, Gregor; Wörgötter, Florentin; Sandamirskaya, Yulia

    2017-01-01

    Dynamic neural fields (DNFs) are dynamical systems models that approximate the activity of large, homogeneous, and recurrently connected neural networks based on a mean field approach. Within dynamic field theory, the DNFs have been used as building blocks in architectures to model sensorimotor embedding of cognitive processes. Typically, the parameters of a DNF in an architecture are manually tuned in order to achieve a specific dynamic behavior (e.g., decision making, selection, or working memory) for a given input pattern. This manual parameters search requires expert knowledge and time to find and verify a suited set of parameters. The DNF parametrization may be particular challenging if the input distribution is not known in advance, e.g., when processing sensory information. In this paper, we propose the autonomous adaptation of the DNF resting level and gain by a learning mechanism of intrinsic plasticity (IP). To enable this adaptation, an input and output measure for the DNF are introduced, together with a hyper parameter to define the desired output distribution. The online adaptation by IP gives the possibility to pre-define the DNF output statistics without knowledge of the input distribution and thus, also to compensate for changes in it. The capabilities and limitations of this approach are evaluated in a number of experiments.

  3. Poisson's Ratio and Intrinsic Plasticity of Metallic Glasses

    NASA Astrophysics Data System (ADS)

    Poon, S. J.; Zhu, Aiwu; Shiflet, G. J.

    2008-06-01

    Through a comparison of the activation barrier densities for plastic deformation and brittle fracture at the yield point, a condition for intrinsic plasticity versus brittleness of metallic glasses under shear loading is derived. The quantitative role of Poisson's ratio ν on fracture is revealed and additional effects due to local shear modulus (G) fluctuations are pointed out. The findings account for the onset of plasticity near reported ν values, as well as the brittleness of some high-ν alloys. Structural relaxation increases G and reduces fluctuations, incurring dual adverse effects on ductility. Implications for designing ductile metallic glasses are discussed.

  4. Plastic Deformation Influence on Intrinsic Magnetic Field of Austenitic Biomaterials

    NASA Astrophysics Data System (ADS)

    Smetana, Milan; Čápová, Klára; Chudáčik, Vladimír; Palček, Peter; Oravcová, Monika

    2016-12-01

    This article deals with non-destructive evaluation of austenitic stainless steels, which are used as the biomaterials in medical practice. Intrinsic magnetic field is investigated using the fluxgate sensor, after the applied plastic deformation. The three austenitic steel types are studied under the same conditions, while several values of the deformation are applied, respectively. The obtained results are presented and discussed in the paper.

  5. Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain.

    PubMed

    Ono, Munenori; Bishop, Deborah C; Oliver, Douglas L

    2016-02-12

    Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound.

  6. Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain

    PubMed Central

    Ono, Munenori; Bishop, Deborah C.; Oliver, Douglas L.

    2016-01-01

    Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound. PMID:26867811

  7. Sensory Deprivation Triggers Synaptic and Intrinsic Plasticity in the Hippocampus.

    PubMed

    Milshtein-Parush, Hila; Frere, Samuel; Regev, Limor; Lahav, Coren; Benbenishty, Amit; Ben-Eliyahu, Shamgar; Goshen, Inbal; Slutsky, Inna

    2017-06-01

    Hippocampus, a temporal lobe structure involved in learning and memory, receives information from all sensory modalities. Despite extensive research on the role of sensory experience in cortical map plasticity, little is known about whether and how sensory experience regulates functioning of the hippocampal circuits. Here, we show that 9 ± 2 days of whisker deprivation during early mouse development depresses activity of CA3 pyramidal neurons by several principal mechanisms: decrease in release probability, increase in the fraction of silent synapses, and reduction in intrinsic excitability. As a result of deprivation-induced presynaptic inhibition, CA3-CA1 synaptic facilitation was augmented at high frequencies, shifting filtering properties of synapses. The changes in the AMPA-mediated synaptic transmission were accompanied by an increase in NR2B-containing NMDA receptors and a reduction in the AMPA/NMDA ratio. The observed reconfiguration of the CA3-CA1 connections may represent a homeostatic adaptation to augmentation in synaptic activity during the initial deprivation phase. In adult mice, tactile disuse diminished intrinsic excitability without altering synaptic facilitation. We suggest that sensory experience regulates computations performed by the hippocampus by tuning its synaptic and intrinsic characteristics. © The Author 2017. Published by Oxford University Press.

  8. Learning to learn - intrinsic plasticity as a metaplasticity mechanism for memory formation.

    PubMed

    Sehgal, Megha; Song, Chenghui; Ehlers, Vanessa L; Moyer, James R

    2013-10-01

    "Use it or lose it" is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity - a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability - this can prevent or provide treatment for cognitive decline not only in patients with clinical disorders but

  9. Learning to learn – intrinsic plasticity as a metaplasticity mechanism for memory formation

    PubMed Central

    Sehgal, Megha; Song, Chenghui; Ehlers, Vanessa L.; Moyer, James R.

    2013-01-01

    “Use it or lose it” is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity – a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability – this can prevent or provide treatment for cognitive decline not only in patients with clinical

  10. Composition Effect on Intrinsic Plasticity or Brittleness in Metallic Glasses

    PubMed Central

    Zhao, Yuan-Yun; Inoue, Akihisa; Chang, Chuntao; Liu, Jian; Shen, Baolong; Wang, Xinmin; Li, Run-Wei

    2014-01-01

    The high plasticity of metallic glasses is highly desirable for a wide range of novel engineering applications. However, the physical origin of the ductile/brittle behaviour of metallic glasses with various compositions and thermal histories has not been fully clarified. Here we have found that metallic glasses with compositions at or near intermetallic compounds, in contrast to the ones at or near eutectics, are extremely ductile and also insensitive to annealing-induced embrittlement. We have also proposed a close correlation between the element distribution features and the plasticity of metallic glasses by tracing the evolutions of the element distribution rearrangement and the corresponding potential energy change within the sliding shear band. These novel results provide useful and universal guidelines to search for new ductile metallic glasses at or near the intermetallic compound compositions in a number of glass-forming alloy systems. PMID:25043428

  11. Long-lasting desynchronization in rat hippocampal slice induced by coordinated reset stimulation

    SciTech Connect

    Tass, P. A.; Barnikol, U. B.; Department of Stereotaxic and Functional Neurosurgery, University of Cologne, D-50931 Cologne

    2009-07-15

    In computational models it has been shown that appropriate stimulation protocols may reshape the connectivity pattern of neural or oscillator networks with synaptic plasticity in a way that the network learns or unlearns strong synchronization. The underlying mechanism is that a network is shifted from one attractor to another, so that long-lasting stimulation effects are caused which persist after the cessation of stimulation. Here we study long-lasting effects of multisite electrical stimulation in a rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that desynchronizing coordinated reset stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with amore » widespread decrease in the amplitude of the epileptiform activity. In contrast, periodic stimulation induces a long-lasting increase in both synchronization and amplitude.« less

  12. Long-lasting desynchronization in rat hippocampal slice induced by coordinated reset stimulation

    SciTech Connect

    Tass, P. A.; Barnikol, U. B.; Silchenko, A. N.; Hauptmann, C.; Speckmann, E.-J.

    2009-07-15

    In computational models it has been shown that appropriate stimulation protocols may reshape the connectivity pattern of neural or oscillator networks with synaptic plasticity in a way that the network learns or unlearns strong synchronization. The underlying mechanism is that a network is shifted from one attractor to another, so that long-lasting stimulation effects are caused which persist after the cessation of stimulation. Here we study long-lasting effects of multisite electrical stimulation in a rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that desynchronizing coordinated reset stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with a widespread decrease in the amplitude of the epileptiform activity. In contrast, periodic stimulation induces a long-lasting increase in both synchronization and amplitude.

  13. Intrinsic Plasticity for Natural Competition in Koniocortex-Like Neural Networks.

    PubMed

    Peláez, Francisco Javier Ropero; Aguiar-Furucho, Mariana Antonia; Andina, Diego

    2016-08-01

    In this paper, we use the neural property known as intrinsic plasticity to develop neural network models that resemble the koniocortex, the fourth layer of sensory cortices. These models evolved from a very basic two-layered neural network to a complex associative koniocortex network. In the initial network, intrinsic and synaptic plasticity govern the shifting of the activation function, and the modification of synaptic weights, respectively. In this first version, competition is forced, so that the most activated neuron is arbitrarily set to one and the others to zero, while in the second, competition occurs naturally due to inhibition between second layer neurons. In the third version of the network, whose architecture is similar to the koniocortex, competition also occurs naturally owing to the interplay between inhibitory interneurons and synaptic and intrinsic plasticity. A more complex associative neural network was developed based on this basic koniocortex-like neural network, capable of dealing with incomplete patterns and ideally suited to operating similarly to a learning vector quantization network. We also discuss the biological plausibility of the networks and their role in a more complex thalamocortical model.

  14. Computational modeling of spiking neural network with learning rules from STDP and intrinsic plasticity

    NASA Astrophysics Data System (ADS)

    Li, Xiumin; Wang, Wei; Xue, Fangzheng; Song, Yongduan

    2018-02-01

    Recently there has been continuously increasing interest in building up computational models of spiking neural networks (SNN), such as the Liquid State Machine (LSM). The biologically inspired self-organized neural networks with neural plasticity can enhance the capability of computational performance, with the characteristic features of dynamical memory and recurrent connection cycles which distinguish them from the more widely used feedforward neural networks. Despite a variety of computational models for brain-like learning and information processing have been proposed, the modeling of self-organized neural networks with multi-neural plasticity is still an important open challenge. The main difficulties lie in the interplay among different forms of neural plasticity rules and understanding how structures and dynamics of neural networks shape the computational performance. In this paper, we propose a novel approach to develop the models of LSM with a biologically inspired self-organizing network based on two neural plasticity learning rules. The connectivity among excitatory neurons is adapted by spike-timing-dependent plasticity (STDP) learning; meanwhile, the degrees of neuronal excitability are regulated to maintain a moderate average activity level by another learning rule: intrinsic plasticity (IP). Our study shows that LSM with STDP+IP performs better than LSM with a random SNN or SNN obtained by STDP alone. The noticeable improvement with the proposed method is due to the better reflected competition among different neurons in the developed SNN model, as well as the more effectively encoded and processed relevant dynamic information with its learning and self-organizing mechanism. This result gives insights to the optimization of computational models of spiking neural networks with neural plasticity.

  15. A Unifying Framework of Synaptic and Intrinsic Plasticity in Neural Populations.

    PubMed

    Leugering, Johannes; Pipa, Gordon

    2018-01-17

    A neuronal population is a computational unit that receives a multivariate, time-varying input signal and creates a related multivariate output. These neural signals are modeled as stochastic processes that transmit information in real time, subject to stochastic noise. In a stationary environment, where the input signals can be characterized by constant statistical properties, the systematic relationship between its input and output processes determines the computation carried out by a population. When these statistical characteristics unexpectedly change, the population needs to adapt to its new environment if it is to maintain stable operation. Based on the general concept of homeostatic plasticity, we propose a simple compositional model of adaptive networks that achieve invariance with regard to undesired changes in the statistical properties of their input signals and maintain outputs with well-defined joint statistics. To achieve such invariance, the network model combines two functionally distinct types of plasticity. An abstract stochastic process neuron model implements a generalized form of intrinsic plasticity that adapts marginal statistics, relying only on mechanisms locally confined within each neuron and operating continuously in time, while a simple form of Hebbian synaptic plasticity operates on synaptic connections, thus shaping the interrelation between neurons as captured by a copula function. The combined effect of both mechanisms allows a neuron population to discover invariant representations of its inputs that remain stable under a wide range of transformations (e.g., shifting, scaling and (affine linear) mixing). The probabilistic model of homeostatic adaptation on a population level as presented here allows us to isolate and study the individual and the interaction dynamics of both mechanisms of plasticity and could guide the future search for computationally beneficial types of adaptation.

  16. Fear extinction induces mGluR5-mediated synaptic and intrinsic plasticity in infralimbic neurons

    PubMed Central

    Sepulveda-Orengo, Marian T.; Lopez, Ana V.; Soler-Cedeño, Omar; Porter, James T.

    2013-01-01

    Studies suggest that plasticity in the infralimbic prefrontal cortex (IL) in rodents and its homolog in humans is necessary for inhibition of fear during the recall of fear extinction. The recall of extinction is impaired by locally blocking metabotropic glutamate receptor type 5 (mGluR5) activation in IL during extinction training. This finding suggests that mGluR5 stimulation may lead to IL plasticity needed for fear extinction. To test this hypothesis, we recorded AMPA and NMDA currents, AMPA receptor rectification, and intrinsic excitability in IL pyramidal neurons in slices from trained rats using whole-cell patch-clamp. We observed that fear extinction increases the AMPA/NMDA ratio, consistent with insertion of AMPA receptors into IL synapses. In addition, extinction training increased inward rectification, suggesting that extinction induces the insertion of calcium-permeable (GluA2-lacking) AMPA receptors into IL synapses. Consistent with this, selectively blocking calcium-permeable AMPA receptors with Naspm reduced the AMPA EPSCs in IL neurons to a larger degree after extinction. Extinction-induced changes in AMPA/NMDA ratio, rectification, and intrinsic excitability were blocked with an mGluR5 antagonist. Together, these findings suggest that mGluR5 activation leads to consolidation of fear extinction by regulating the intrinsic excitability of IL neurons and modifying the composition of AMPA receptors in IL synapses. Consequently, impaired mGluR5 activity in IL synapses could be one factor that causes inappropriate modulation of fear expression leading to anxiety disorders. PMID:23616528

  17. Colorful Demos with a Long-Lasting Soap Bubble.

    ERIC Educational Resources Information Center

    Behroozi, F.; Olson, D. W.

    1994-01-01

    Describes several demonstrations that feature interaction of light with soap bubbles. Includes directions about how to produce a long-lasting stationary soap bubble with an easily changeable size and describes the interaction of white light with the bubble. (DDR)

  18. Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression

    PubMed Central

    Ramiro-Cortés, Yazmín; Israely, Inbal

    2013-01-01

    Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation. PMID:23951097

  19. Plasticity of the intrinsic period of the human circadian timing system.

    PubMed

    Scheer, Frank A J L; Wright, Kenneth P; Kronauer, Richard E; Czeisler, Charles A

    2007-08-08

    Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol), which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light ( approximately 450 lux; approximately 1.2 W/m(2)) for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration.

  20. Familiarity Detection is an Intrinsic Property of Cortical Microcircuits with Bidirectional Synaptic Plasticity

    PubMed Central

    2017-01-01

    Abstract Humans instantly recognize a previously seen face as “familiar.” To deepen our understanding of familiarity-novelty detection, we simulated biologically plausible neural network models of generic cortical microcircuits consisting of spiking neurons with random recurrent synaptic connections. NMDA receptor (NMDAR)-dependent synaptic plasticity was implemented to allow for unsupervised learning and bidirectional modifications. Network spiking activity evoked by sensory inputs consisting of face images altered synaptic efficacy, which resulted in the network responding more strongly to a previously seen face than a novel face. Network size determined how many faces could be accurately recognized as familiar. When the simulated model became sufficiently complex in structure, multiple familiarity traces could be retained in the same network by forming partially-overlapping subnetworks that differ slightly from each other, thereby resulting in a high storage capacity. Fisher’s discriminant analysis was applied to identify critical neurons whose spiking activity predicted familiar input patterns. Intriguingly, as sensory exposure was prolonged, the selected critical neurons tended to appear at deeper layers of the network model, suggesting recruitment of additional circuits in the network for incremental information storage. We conclude that generic cortical microcircuits with bidirectional synaptic plasticity have an intrinsic ability to detect familiar inputs. This ability does not require a specialized wiring diagram or supervision and can therefore be expected to emerge naturally in developing cortical circuits. PMID:28534043

  1. The plasticity of intrinsic functional connectivity patterns associated with rehabilitation intervention in chronic stroke patients.

    PubMed

    Zheng, Xiaohui; Sun, Limin; Yin, Dazhi; Jia, Jie; Zhao, Zhiyong; Jiang, Yuwei; Wang, Xiangmin; Wu, Jie; Gong, Jiayu; Fan, Mingxia

    2016-04-01

    It has been demonstrated that rehabilitative interventions can promote motor function recovery in stroke patients. However, little is known regarding the neural mechanisms that underlie the rehabilitation treatments. The aim of this study was to investigate the plasticity of intrinsic functional connectivity patterns that are associated with rehabilitation intervention in chronic stroke patients. Twelve chronic stroke patients with subcortical lesions in the left motor pathway participated in a 4-week rehabilitation intervention and underwent resting-state functional magnetic resonance imaging (fMRI) scanning before and after the intervention. Both functional connectivity analyses of the ipsilesional (left) primary motor cortex (M1) and measurements of the lateralization index of the connectivity patterns were performed in both the stroke patients and healthy controls (HC). Compared with the HC, the decreased connectivity of the ipsilesional M1 with the contralesional sensorimotor cortex (SMC), bilateral supplementary motor areas, and inferior parietal lobule due to stroke were remarkably restored after the intervention. More specifically, the lateralization index of the bilateral SMC tends to be the normal level. Moreover, comparing post- with pre-intervention, we observed significantly increased connectivity of ipsilesional M1 with the contralesional M1 and medial superior frontal gyrus (mSFG). Additionally, the index of pre-intervention connectivity with the contralesional mSFG was positively correlated with motor improvement. The impact of rehabilitation intervention on intrinsic functional connectivity patterns throughout the brain was measurable on resting-state fMRI, and systematic assessment of resting-state functional connectivity can provide prognostic insight for later motor improvement.

  2. Tissue engineering: creation of long-lasting blood vessels.

    PubMed

    Koike, Naoto; Fukumura, Dai; Gralla, Oliver; Au, Patrick; Schechner, Jeffrey S; Jain, Rakesh K

    2004-03-11

    The construction of stable blood vessels is a fundamental challenge for tissue engineering in regenerative medicine. Although certain genes can be introduced into vascular cells to enhance their survival and proliferation, these manipulations may be oncogenic. We show here that a network of long-lasting blood vessels can be formed in mice by co-implantation of vascular endothelial cells and mesenchymal precursor cells, by-passing the need for risky genetic manipulations. These networks are stable and functional for one year in vivo.

  3. Is Choice-Induced Preference Change Long Lasting?

    PubMed Central

    Yu, Xiaoyu; Koster, Raphael; Dolan, Raymond J.

    2013-01-01

    The idea that decisions alter preferences has had a considerable influence on the field of psychology and underpins cognitive dissonance theory. Yet it is unknown whether choice-induced changes in preferences are long lasting or are transient manifestations seen in the immediate aftermath of decisions. In the research reported here, we investigated whether these changes in preferences are fleeting or stable. Participants rated vacation destinations immediately after making hypothetical choices between destinations and 2.5 to 3 years later. We found that choices altered preferences both immediately and after the delay. These changes could not be accounted for by participants’ preexisting preferences, and they occurred only when participants made the choices themselves. Our findings provide evidence that making a decision can lead to enduring change in preferences. PMID:22933456

  4. Is choice-induced preference change long lasting?

    PubMed

    Sharot, Tali; Fleming, Stephen M; Yu, Xiaoyu; Koster, Raphael; Dolan, Raymond J

    2012-10-01

    The idea that decisions alter preferences has had a considerable influence on the field of psychology and underpins cognitive dissonance theory. Yet it is unknown whether choice-induced changes in preferences are long lasting or are transient manifestations seen in the immediate aftermath of decisions. In the research reported here, we investigated whether these changes in preferences are fleeting or stable. Participants rated vacation destinations before making hypothetical choices between destinations, immediately afterward, and 2.5 to 3 years later. We found that choices altered preferences both immediately after being made and after the delay. These changes could not be accounted for by participants' preexisting preferences, and they occurred only when participants made the choices themselves. Our findings provide evidence that making a decision can lead to enduring change in preferences.

  5. Characterizing Interplanetary Structures of Long-Lasting Ionospheric Storm Events

    NASA Astrophysics Data System (ADS)

    Tandoi, C.; Dong, Y.; Ngwira, C. M.; Damas, M. C.

    2015-12-01

    Geomagnetic storms can result in periods of heightened TEC (Total Electron Content) in Earth's ionosphere. These periods of change in TEC (dTEC) can have adverse impacts on a technological society, such as scintillation of radio signals used by communication and navigation satellites. However, it is unknown which exact properties of a given storm cause dTEC. We are comparing different solar wind properties that result in a significant long-lasting dTEC to see if there are any patterns that remain constant in these storms. These properties, among others, include the interplanetary magnetic field By and Bz components, the proton density, and the flow speed. As a preliminary investigation, we have studied 15 solar storms. Preliminary results will be presented. In the future, we hope to increase our sample size and analyze over 80 different solar storms, which result in significant dTEC.

  6. Long-lasting subjective effects of LSD in normal subjects.

    PubMed

    Schmid, Yasmin; Liechti, Matthias E

    2018-02-01

    Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality. We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI). On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found. In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had

  7. Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

    PubMed Central

    Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

    2015-01-01

    The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations. PMID:26125597

  8. Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

    PubMed

    Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

    2015-06-01

    The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.

  9. The fabrication and characterization of flexible single-crystalline silicon and germanium p-intrinsic-n photodetectors on plastic substrates

    NASA Astrophysics Data System (ADS)

    Dang, Mengjiao; Yuan, Hao-Chih; Ma, Zhenqiang; Ma, Jianguo; Qin, Guoxuan

    2017-06-01

    The flexible photodetector is the essential device for many of the optoelectronic applications and its performance can be influenced by a number of factors, including semiconductor materials, illumination conditions, device structures, etc. Therefore, in order to better design and use the flexible photodetectors, it is necessary to understand how these factors affect their performance. In this study, we fabricated flexible lateral p-intrinsic-n photodetectors formed with single-crystalline silicon and germanium nanomembranes on polyethylene terephthalate substrates. The performance of the flexible photodetectors with various dimensions is presented under different illumination conditions. The influences of different semiconductor materials, illumination conditions (wavelength and power of the incident light), and dimensions of the intrinsic region (length and width) on the photocurrent and efficiency are investigated, and the underlying mechanisms are studied based on experimental, simulation, and theoretical analysis. The results provide guidelines for the design and fabrication of flexible single-crystalline semiconductor photodetectors on the plastic substrates.

  10. Long lasting effects of chronic heavy cannabis abuse.

    PubMed

    Nestoros, Joannis N; Vakonaki, Elena; Tzatzarakis, Manolis N; Alegakis, Athanasios; Skondras, Markos D; Tsatsakis, Aristidis M

    2017-06-01

    The purpose of this study was to evaluate the extent of short-term memory impairment and schizophrenia-like symptoms in heavy and systematic cannabis users and the association between the severity of abuse and the longevity of its persistent symptoms after refraining from such use. A complete psychiatric examination and a psychometric evaluation were performed in 48 solely cannabis users. Additionally, head hair samples were analyzed and the detected cannabinoids levels were correlated with the psychometric findings. A total of 33.3% (n = 16) of the total examined cannabis users were currently imprisoned. The years of abuse ranged from 1 to 35 years and the median daily dose was 5.84.4 gr and 4.84.0 gr for prisoners (n = 16) and non prisoners (n = 32), respectively. A total of 39.6% of the users experienced hallucinations (mostly auditory), 54.2% experienced delusions (mostly ideas of reference and persecution), 85.4% had organic brain dysfunction in a test addressing visual-motor functioning and visual perception skills, and all users (100%) were found to have organic brain dysfunction in a test of visual memory immediate recall. The cannabinoid metabolite levels in the hair samples were consistent with the reported history of substance abuse and total grams of consumption for the participants below 35 years old (p < .001). Statistically elevated cannabinoids levels were observed in users with auditory hallucinations compared to users without any hallucinations (p = .019). The existence of hallucinations, delusions, and organic brain dysfunction in heavy cannabis users seems to be associated with cannabinoid levels in hair. The continuation of persistent symptoms 3 months after the discontinuation of cannabis abuse, was a remarkable finding. We provide evidence that chronic and heavy cannabis abuse results in long-lasting brain dysfunction in all users and in long-lasting schizophrenia-like psychotic symptoms in more than half of all users

  11. Immunogenicity of long-lasting recombinant factor VIII products.

    PubMed

    Ing, Mathieu; Gupta, Nimesh; Teyssandier, Maud; Maillère, Bernard; Pallardy, Marc; Delignat, Sandrine; Lacroix-Desmazes, Sébastien

    2016-03-01

    Replacement therapy for patients with hemophilia A using plasma-derived or recombinant factor VIII (FVIII) is complicated by the short half-life of the FVIII products and by the occurrence of neutralizing antibodies in a substantial number of patients. In the recent years, enormous efforts have been invested to develop new generations of coagulation factors with extended half-lives. Presumably, the use of long-lasting FVIII products should reduce the frequency of administration to the patients and drastically improve their quality of life. The question of their immunogenicity remains however unanswered as yet. The present review proposes a summary of the different strategies developed to enhance the half-life of FVIII, including fusion of FVIII to the Fc fragment of the human IgG1 or to human serum albumin, or attachment of polyethylene glycol. Based on the available literature, we hypothesize on the potential benefits or risks associated with each of the latter strategies in terms of immunogenicity of the newly derived hemostatic drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Early visual learning induces long-lasting connectivity changes during rest in the human brain

    PubMed Central

    Urner, Maren; Schwarzkopf, Dietrich Samuel; Friston, Karl; Rees, Geraint

    2013-01-01

    Spontaneous fluctuations in resting state activity can change in response to experience-dependent plasticity and learning. Visual learning is fast and can be elicited in an MRI scanner. Here, we showed that a random dot motion coherence task can be learned within one training session. While the task activated primarily visual and parietal brain areas, learning related changes in neural activity were observed in the hippocampus. Crucially, even this rapid learning affected resting state dynamics both immediately after the learning and 24 h later. Specifically, the hippocampus changed its coupling with the striatum, in a way that was best explained as a consolidation of early learning related changes. Our findings suggest that long-lasting changes in neuronal coupling are accompanied by changes in resting state activity. PMID:23558105

  13. Early visual learning induces long-lasting connectivity changes during rest in the human brain.

    PubMed

    Urner, Maren; Schwarzkopf, Dietrich Samuel; Friston, Karl; Rees, Geraint

    2013-08-15

    Spontaneous fluctuations in resting state activity can change in response to experience-dependent plasticity and learning. Visual learning is fast and can be elicited in an MRI scanner. Here, we showed that a random dot motion coherence task can be learned within one training session. While the task activated primarily visual and parietal brain areas, learning related changes in neural activity were observed in the hippocampus. Crucially, even this rapid learning affected resting state dynamics both immediately after the learning and 24h later. Specifically, the hippocampus changed its coupling with the striatum, in a way that was best explained as a consolidation of early learning related changes. Our findings suggest that long-lasting changes in neuronal coupling are accompanied by changes in resting state activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Long-lasting increase in axonal excitability after epidurally applied DC.

    PubMed

    Jankowska, Elzbieta; Kaczmarek, Dominik; Bolzoni, Francesco; Hammar, Ingela

    2017-08-01

    Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result

  15. Long-lasting virtual motorcycle-riding trainer effectiveness

    PubMed Central

    Vidotto, Giulio; Tagliabue, Mariaelena; Tira, Michael D.

    2015-01-01

    This work aimed to test the long-lasting effects of learning acquired with a virtual motorcycle-riding trainer as a tool to improve hazard perception. During the simulation, the rider can interact with other road actors and experience the most common potential accident situations in order to learn to modify his or her behavior to anticipate hazards and avoid crashes. We compared performance to the riding simulator of the two groups of participants: the experimental group, which was trained with the same simulator one year prior, and the control group that had not received any type of training with a riding or driving simulator. All of the participants had ridden a moped in the previous 12 months. The experimental group showed greater abilities to avoid accidents and recognize hazards in comparison to their performance observed a year before, whereas the performance of the control group was similar to that of the experimental group 1 year before in the first two sessions, and even better in the third. We interpreted this latter result as a consequence of their prior on-road experience. Also, the fact that the performance of the experimental group at the beginning of the follow-up is better than that recorded at the end of the training—1 year before—is in line with the idea of a transfer from the on-road experience to the simulator. The present data confirm our main expectation that the effectiveness of the riding training simulator on the ability to cope with potentially dangerous situations persists over time and provides additional evidence in favor of the idea that simulators may be considered useful tools for training the ability to detect and react to hazards, leading to an improvement of this higher-order cognitive skill that persists over time. Implications for the reciprocal influence of the training with the simulator and the on-the road experience are discussed as well. PMID:26579036

  16. Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity

    PubMed Central

    Leposavić, Gordana Momčilo; Pilipović, Ivan M.

    2018-01-01

    The thymus is sexually differentiated organ providing microenvironment for T-cell precursor differentiation/maturation in the major histocompatibility complex-restricted self-tolerant T cells. With increasing age, the thymus undergoes involution leading to the decline in efficacy of thymopoiesis. Noradrenaline from thymic nerve fibers and “(nor)adrenergic” cells is involved in the regulation of thymopoiesis. In rodents, noradrenaline concentration in thymus and adrenoceptor (AR) expression on thymic cells depend on sex and age. These differences are suggested to be implicated in the development of sexual diergism and the age-related decline in thymopoiesis. The programming of both thymic sexual differentiation and its involution occurs during the critical early perinatal period and may be reprogrammed during peripubertal development. The thymic (re)programming is critically dependent on circulating levels of gonadal steroids. Although the underlying molecular mechanisms have not yet been elucidated fully, it is assumed that the gonadal steroid action during the critical perinatal/peripubertal developmental periods leads to long-lasting changes in the efficacy of thymopoiesis partly through (re)programming of “(nor)adrenergic” cell networks and AR expression on thymic cells. PMID:29441042

  17. FIELD TOPOLOGY ANALYSIS OF A LONG-LASTING CORONAL SIGMOID

    SciTech Connect

    Savcheva, A. S.; Van Ballegooijen, A. A.; DeLuca, E. E., E-mail: savcheva@bu.edu

    2012-01-01

    We present the first field topology analysis based on nonlinear force-free field (NLFFF) models of a long-lasting coronal sigmoid observed in 2007 February with the X-Ray Telescope on Hinode. The NLFFF models are built with the flux rope insertion method and give the three-dimensional coronal magnetic field as constrained by observed coronal loop structures and photospheric magnetograms. Based on these models, we have computed horizontal maps of the current and the squashing factor Q for 25 different heights in the corona for all six days of the evolution of the region. We use the squashing factor to quantify the degreemore » of change of the field line linkage and to identify prominent quasi-separatrix layers (QSLs). We discuss the major properties of these QSL maps and devise a way to pick out important QSLs since our calculation cannot reach high values of Q. The complexity in the QSL maps reflects the high degree of fragmentation of the photospheric field. We find main QSLs and current concentrations that outline the flux rope cavity and that become characteristically S-shaped during the evolution of the sigmoid. We note that, although intermittent bald patches exist along the length of the sigmoid during its whole evolution, the flux rope remains stable for several days. However, shortly after the topology of the field exhibits hyperbolic flux tubes (HFT) on February 7 and February 12 the sigmoid loses equilibrium and produces two B-class flares and associated coronal mass ejections (CMEs). The location of the most elevated part of the HFT in our model coincides with the inferred locations of the two flares. Therefore, we suggest that the presence of an HFT in a coronal magnetic configuration may be an indication that the system is ready to erupt. We offer a scenario in which magnetic reconnection at the HFT drives the system toward the marginally stable state. Once this state is reached, loss of equilibrium occurs via the torus instability, producing a CME.« less

  18. Field Topology Analysis of a Long-lasting Coronal Sigmoid

    NASA Astrophysics Data System (ADS)

    Savcheva, A. S.; van Ballegooijen, A. A.; DeLuca, E. E.

    2012-01-01

    We present the first field topology analysis based on nonlinear force-free field (NLFFF) models of a long-lasting coronal sigmoid observed in 2007 February with the X-Ray Telescope on Hinode. The NLFFF models are built with the flux rope insertion method and give the three-dimensional coronal magnetic field as constrained by observed coronal loop structures and photospheric magnetograms. Based on these models, we have computed horizontal maps of the current and the squashing factor Q for 25 different heights in the corona for all six days of the evolution of the region. We use the squashing factor to quantify the degree of change of the field line linkage and to identify prominent quasi-separatrix layers (QSLs). We discuss the major properties of these QSL maps and devise a way to pick out important QSLs since our calculation cannot reach high values of Q. The complexity in the QSL maps reflects the high degree of fragmentation of the photospheric field. We find main QSLs and current concentrations that outline the flux rope cavity and that become characteristically S-shaped during the evolution of the sigmoid. We note that, although intermittent bald patches exist along the length of the sigmoid during its whole evolution, the flux rope remains stable for several days. However, shortly after the topology of the field exhibits hyperbolic flux tubes (HFT) on February 7 and February 12 the sigmoid loses equilibrium and produces two B-class flares and associated coronal mass ejections (CMEs). The location of the most elevated part of the HFT in our model coincides with the inferred locations of the two flares. Therefore, we suggest that the presence of an HFT in a coronal magnetic configuration may be an indication that the system is ready to erupt. We offer a scenario in which magnetic reconnection at the HFT drives the system toward the marginally stable state. Once this state is reached, loss of equilibrium occurs via the torus instability, producing a CME.

  19. Long-lasting antifouling coating from multi-armed polymer.

    PubMed

    Mizrahi, Boaz; Khoo, Xiaojuan; Chiang, Homer H; Sher, Katalina J; Feldman, Rose G; Lee, Jung-Jae; Irusta, Silvia; Kohane, Daniel S

    2013-08-13

    We describe a new antifouling surface coating, based on aggregation of a short amphiphilic four-armed PEG-dopamine polymer into particles and on surface binding by catechol chemistry. An unbroken and smooth polymeric coating layer with an average thickness of approximately 4 μm was formed on top of titanium oxide surfaces by a single step reaction. Coatings conferred excellent resistance to protein adhesion. Cell attachment was completely prevented for at least eight weeks, although the membranes themselves did not appear to be intrinsically cytotoxic. When linear PEG or four-armed PEG of higher molecular weight were used, the resulting coatings were inferior in thickness and in preventing protein adhesion. This coating method has potential applicability for biomedical devices susceptible to fouling after implantation.

  20. Long-lasting Antifouling Coating from Multi-Armed Polymer

    PubMed Central

    Mizrahi, Boaz; Khoo, Xiaojuan; Chaing, Homer H.; Sher, Katalina J.; Feldman, Rose G.; Lee, Jung-Jae; Irusta, Silvia; Kohane, Daniel S.

    2013-01-01

    We describe a new antifouling surface coating, based on aggregation of a short amphiphilic four-armed PEG-dopamine polymer into particles, and on surface binding by catechol chemistry. An unbroken and smooth polymeric coating layer with an average thickness of approximately 4 microns was formed on top of titanium oxide surfaces by a single step reaction. Coatings conferred excellent resistance to protein adhesion. Cell attachment was completely prevented for at least eight weeks, although the membranes themselves did not appear to be intrinsically cytotoxic. When linear PEG or four-armed PEG of higher molecular weight were used, the resulting coatings were inferior in thickness and in preventing protein adhesion. This coating method has potential applicability for biomedical devices susceptible to fouling after implantation. PMID:23855875

  1. Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD.

    PubMed

    Ma, Tengfei; Cheng, Yifeng; Roltsch Hellard, Emily; Wang, Xuehua; Lu, Jiayi; Gao, Xinsheng; Huang, Cathy C Y; Wei, Xiao-Yan; Ji, Jun-Yuan; Wang, Jun

    2018-02-12

    Addiction is proposed to arise from alterations in synaptic strength via mechanisms of long-term potentiation (LTP) and depression (LTD). However, the causality between these synaptic processes and addictive behaviors is difficult to demonstrate. Here we report that LTP and LTD induction altered operant alcohol self-administration, a motivated drug-seeking behavior. We first induced LTP by pairing presynaptic glutamatergic stimulation with optogenetic postsynaptic depolarization in the dorsomedial striatum, a brain region known to control goal-directed behavior. Blockade of this LTP by NMDA-receptor inhibition unmasked an endocannabinoid-dependent LTD. In vivo application of the LTP-inducing protocol caused a long-lasting increase in alcohol-seeking behavior, while the LTD protocol decreased this behavior. We further identified that optogenetic LTP and LTD induction at cortical inputs onto striatal dopamine D1 receptor-expressing neurons controlled these behavioral changes. Our results demonstrate a causal link between synaptic plasticity and alcohol-seeking behavior and suggest that modulation of this plasticity may inspire a therapeutic strategy for addiction.

  2. Evidence for rRNA 2'-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes.

    PubMed

    Erales, Jenny; Marchand, Virginie; Panthu, Baptiste; Gillot, Sandra; Belin, Stéphane; Ghayad, Sandra E; Garcia, Maxime; Laforêts, Florian; Marcel, Virginie; Baudin-Baillieu, Agnès; Bertin, Pierre; Couté, Yohann; Adrait, Annie; Meyer, Mélanie; Therizols, Gabriel; Yusupov, Marat; Namy, Olivier; Ohlmann, Théophile; Motorin, Yuri; Catez, Frédéric; Diaz, Jean-Jacques

    2017-12-05

    Ribosomal RNAs (rRNAs) are main effectors of messenger RNA (mRNA) decoding, peptide-bond formation, and ribosome dynamics during translation. Ribose 2'-O-methylation (2'-O-Me) is the most abundant rRNA chemical modification, and displays a complex pattern in rRNA. 2'-O-Me was shown to be essential for accurate and efficient protein synthesis in eukaryotic cells. However, whether rRNA 2'-O-Me is an adjustable feature of the human ribosome and a means of regulating ribosome function remains to be determined. Here we challenged rRNA 2'-O-Me globally by inhibiting the rRNA methyl-transferase fibrillarin in human cells. Using RiboMethSeq, a nonbiased quantitative mapping of 2'-O-Me, we identified a repertoire of 2'-O-Me sites subjected to variation and demonstrate that functional domains of ribosomes are targets of 2'-O-Me plasticity. Using the cricket paralysis virus internal ribosome entry site element, coupled to in vitro translation, we show that the intrinsic capability of ribosomes to translate mRNAs is modulated through a 2'-O-Me pattern and not by nonribosomal actors of the translational machinery. Our data establish rRNA 2'-O-Me plasticity as a mechanism providing functional specificity to human ribosomes.

  3. Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior.

    PubMed

    Kamii, Hironori; Kurosawa, Ryo; Taoka, Naofumi; Shinohara, Fumiya; Minami, Masabumi; Kaneda, Katsuyuki

    2015-05-01

    The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Effect of Spike-Timing-Dependent Plasticity on Intrinsic Coherence Resonance in Newman-Watts Stochastic Hodgkin-Huxley Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Xie, Huijuan; Gong, Yubing; Wang, Qi

    2016-07-01

    In this paper, we numerically study the effect of spike-timing-dependent plasticity (STDP) on coherence resonance (CR) induced by channel noise in adaptive Newman-Watts stochastic Hodgkin-Huxley neuron networks. It is found that STDP can either enhance or suppress the intrinsic CR when the adjusting rate of STDP decreases or increases. STDP can alter the effects of network randomness and network size on the intrinsic CR. Under STDP, for electrical coupling there are optimal network randomness and network size by which the intrinsic CR becomes strongest, however, for chemical coupling the intrinsic CR is always enhanced as network randomness or network size increases, which are different from the results for fixed coupling. These results show that the intrinsic CR of the neuronal networks can be either enhanced or suppressed by STDP, and there are optimal network randomness and network size by which the intrinsic CR becomes strongest. These findings could provide a new insight into the role of STDP for the information processing and transmission in neural systems.

  5. Serotonin 5-HT2 Receptors Induce a Long-Lasting Facilitation of Spinal Reflexes Independent of Ionotropic Receptor Activity

    PubMed Central

    Shay, Barbara L.; Sawchuk, Michael; Machacek, David W.; Hochman, Shawn

    2009-01-01

    Dorsal root-evoked stimulation of sensory afferents in the hemisected in vitro rat spinal cord produces reflex output, recorded on the ventral roots. Transient spinal 5-HT2C receptor activation induces a long-lasting facilitation of these reflexes (LLFR) by largely unknown mechanisms. Two Sprague-Dawley substrains were used to characterize network properties involved in this serotonin (5-HT) receptor-mediated reflex plasticity. Serotonin more easily produced LLFR in one substrain and a long-lasting depression of reflexes (LLDR) in the other. Interestingly, LLFR and LLDR were bidirectionally interconvertible using 5-HT2A/2C and 5-HT1A receptor agonists, respectively, regardless of substrain. LLFR was predominantly Aβ afferent fiber mediated, consistent with prominent 5-HT2C receptor expression in the Aβ fiber projection territories (deeper spinal laminae). Reflex facilitation involved an unmasking of polysynaptic pathways and an increased receptive field size. LLFR emerged even when reflexes were evoked three to five times/h, indicating an activity independent induction. Both the NMDA and AMPA/kainate receptor-mediated components of the reflex could be facilitated, and facilitation was dependent on 5-HT receptor activation alone, not on coincident reflex activation in the presence of 5-HT. Selective blockade of GABAA and/or glycine receptors also did not prevent reflex amplification and so are not required for LLFR. Indeed, a more robust response was seen after blockade of spinal inhibition, indicating that inhibitory processes serve to limit reflex amplification. Overall we demonstrate that the serotonergic system has the capacity to induce long-lasting bidirectional changes in reflex strength in a manner that is nonassociative and independent of evoked activity or activation of ionotropic excitatory and inhibitory receptors. PMID:16033939

  6. 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.

  7. Different cerebral plasticity of intrinsic and extrinsic hand muscles after peripheral neurotization in a patient with brachial plexus injury: A TMS and fMRI study.

    PubMed

    Li, Tie; Hua, Xu-Yun; Zheng, Mou-Xiong; Wang, Wei-Wei; Xu, Jian-Guang; Gu, Yu-Dong; Xu, Wen-Dong

    2015-09-14

    Contralateral C7 (CC7) neurotization has been an important approach for brachial plexus injury (BPI). Patients can achieve relatively good grasping function driven by the proximal extrinsic hand muscle (flexor digitorum, FD) after CC7 neurotization, whereas the thumb opposition function driven by the distal intrinsic muscle (abductor pollicis brevis, APB) is poor. The present study aimed to investigate the brain reorganization patterns of the recovery processes of intrinsic and extrinsic hand functions after repairing the median nerve by CC7 neurotization. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to evaluate the cerebral plasticity in one BPI patient after CC7 neurotization. After the CC7 neurotization, the patient showed improvements in the paralyzed hand. Combination of TMS and fMRI investigations demonstrated different cortical reshaping patterns of APB and FD. It was also found that the activated cortical areas of FD were located in bilateral motor cortices, but the area of APB was only located in ipsilateral motor cortex. The cerebral plasticity procedure appeared to be different in the gross and fine motor function recovery processes. It provided a new perspective into the cerebral plasticity induced by CC7 neurotization. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial.

    PubMed

    Sluydts, Vincent; Durnez, Lies; Heng, Somony; Gryseels, Charlotte; Canier, Lydie; Kim, Saorin; Van Roey, Karel; Kerkhof, Karen; Khim, Nimol; Mao, Sokny; Uk, Sambunny; Sovannaroth, Siv; Grietens, Koen Peeters; Sochantha, Tho; Menard, Didier; Coosemans, Marc

    2016-10-01

    Although effective topical repellents provide personal protection against malaria, whether mass use of topical repellents in addition to long-lasting insecticidal nets can contribute to a further decline of malaria is not known, particularly in areas where outdoor transmission occurs. We aimed to assess the epidemiological efficacy of a highly effective topical repellent in addition to long-lasting insecticidal nets in reducing malaria prevalence in this setting. A cluster randomised controlled trial was done in the 117 most endemic villages in Ratanakiri province, Cambodia, to assess the efficacy of topical repellents in addition to long-lasting insecticidal nets in controlling malaria in a low-endemic setting. We did a pre-trial assessment of village accessibility and excluded four villages because of their inaccessibility during the rainy season. Another 25 villages were grouped because of their proximity to each other, resulting in 98 study clusters (comprising either a single village or multiple neighbouring villages). Clusters were randomly assigned (1:1) to either a control (long-lasting insecticidal nets) or intervention (long-lasting insecticidal nets plus topical repellent) study group after a restricted randomisation. All clusters received one long-lasting insecticidal net per individual, whereas those in the intervention group also received safe and effective topical repellents (picaridin KBR3023, SC Johnson, Racine, WI, USA), along with instruction and promotion of its daily use. Cross-sectional surveys of 65 randomly selected individuals per cluster were done at the beginning and end of the malaria transmission season in 2012 and 2013. The primary outcome was Plasmodium species-specific prevalence in participants obtained by real-time PCR, assessed in the intention-to-treat population. Complete safety analysis data will be published seperately; any ad-hoc adverse events are reported here. This trial is registered with ClinicalTrials.gov, number NCT

  9. Does foreplay matter? Gammarus pulex females may benefit from long-lasting precopulatory mate guarding

    PubMed Central

    Galipaud, Matthias; Dechaume-Moncharmont, François-Xavier; Oughadou, Abderrahim; Bollache, Loïc

    2011-01-01

    Precopulatory mate guarding (PCMG) is generally assumed to be costly for both sexes. However, males may gain by displaying long-lasting mate guarding under strong male–male competition. Surprisingly, the potential for females to benefit from being held by males has been largely overlooked in previous studies. In Gammarus pulex, an amphipod crustacean, PCMG lasts several weeks, yet females are described as bearing only cost from such male mating strategy. We investigated potential female benefits by assessing the effect of mate guarding on her intermoult duration. Unpaired females had longer intermoult duration than paired females. Intermoult duration clearly decreased when paired females engaged in early and long-lasting mate guarding. In addition, short intermoults and long-lasting mate guarding had no effect on egg number. These results highlight a potential benefit associated with PCMG for G. pulex females, suggesting that the strength of an intersexual conflict over its duration may be overestimated. PMID:21068026

  10. Selective Maintenance of Motor Performance in Older Adults from Long-Lasting Sport Practice

    ERIC Educational Resources Information Center

    Dascal, Juliana Bayeux; Teixeira, Luis Augusto

    2016-01-01

    Purpose: Decline of motor performance in older individuals affects their quality of life. Understanding the contribution of sport-related training in advanced ages might help to attenuate motor performance decay as one gets older. The purpose of our study was to evaluate the extent to which long-lasting training in running or sport-specific skills…

  11. DNA vaccination by intradermal electroporation induces long-lasting immune responses in rhesus macaques

    PubMed Central

    Kulkarni, Viraj; Rosati, Margherita; Jalah, Rashmi; Ganneru, Brunda; Alicea, Candido; Yu, Lei; Guan, Yongjun; LaBranche, Celia; Montefiori, David C; King, Alan D; Valentin, Antonio; Pavlakis, George N; Felber, Barbara K

    2014-01-01

    Background A desirable HIV vaccine should induce protective long-lasting humoral and cellular immune responses. Methods Macaques were immunized by env DNA, selected from a panel of recently transmitted SIVmac251 Env using intradermal electroporation as vaccine delivery method and magnitude, breadth and longevity of humoral and cellular immune responses. Results The macaques developed high, long-lasting humoral immune responses with neutralizing capacity against homologous and heterologous Env. The avidity of the antibody responses was also preserved over 1-year follow-up. Analysis of cellular immune responses demonstrated induction of Env-specific memory T cells harboring granzyme B, albeit their overall levels were low. Similar to the humoral responses, the cellular immunity was persistent over the ∼1-year follow-up. Conclusion These data show that vaccination by this intradermal DNA delivery regimen is able to induce potent and durable immune responses in macaques. PMID:24810337

  12. Pink light emitting long-lasting phosphorescence in Sm 3+-doped CdSiO 3

    NASA Astrophysics Data System (ADS)

    Lei, Bingfu; Liu, Yingliang; Liu, Jie; Ye, Zeren; Shi, Chunshan

    2004-04-01

    Novel pink light emitting long-lasting afterglow CdSiO 3:Sm 3+ phosphors are prepared by the conventional high-temperature solid-state method and their luminescent properties are investigated. XRD and photoluminescence (PL) spectra are used to characterize the synthesized phosphors. The phosphors are well crystallized by calcinations at 1050°C for 5 h. These phosphors emit pink light and show long-lasting phosphorescence after they are excited with 254 nm ultraviolet light. The phosphorescence lasts for nearly 5 h in the light perception of the dark-adapted human eye (0.32 mcd/m 2). The phosphorescence mechanism is also investigated. All the results indicate that these phosphors have promising potential practical applications.

  13. Long-Lasting Permethrin-Impregnated Clothing Protects Against Mosquito Bites in Outdoor Workers.

    PubMed

    Londono-Renteria, Berlin; Patel, Jaymin C; Vaughn, Meagan; Funkhauser, Sheana; Ponnusamy, Loganathan; Grippin, Crystal; Jameson, Sam B; Apperson, Charles; Mores, Christopher N; Wesson, Dawn M; Colpitts, Tonya M; Meshnick, Steven R

    2015-10-01

    Outdoor exposure to mosquitoes is a risk factor for many diseases, including malaria and dengue. We have previously shown that long-lasting permethrin-impregnated clothing protects against tick and chigger bites in a double-blind randomized controlled trial in North Carolina outdoor workers. Here, we evaluated whether this clothing is protective against mosquito bites by measuring changes in antibody titers to mosquito salivary gland extracts. On average, there was a 10-fold increase in titer during the spring and summer when mosquito exposure was likely to be the highest. During the first year of the study, the increase in titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of control subjects. This finding suggests that long-lasting permethrin-impregnated clothing provided protection against mosquito bites. © The American Society of Tropical Medicine and Hygiene.

  14. Long-Lasting Permethrin-Impregnated Clothing Protects against Mosquito Bites in Outdoor Workers

    PubMed Central

    Londono-Renteria, Berlin; Patel, Jaymin C.; Vaughn, Meagan; Funkhauser, Sheana; Ponnusamy, Loganathan; Grippin, Crystal; Jameson, Sam B.; Apperson, Charles; Mores, Christopher N.; Wesson, Dawn M.; Colpitts, Tonya M.; Meshnick, Steven R.

    2015-01-01

    Outdoor exposure to mosquitoes is a risk factor for many diseases, including malaria and dengue. We have previously shown that long-lasting permethrin-impregnated clothing protects against tick and chigger bites in a double-blind randomized controlled trial in North Carolina outdoor workers. Here, we evaluated whether this clothing is protective against mosquito bites by measuring changes in antibody titers to mosquito salivary gland extracts. On average, there was a 10-fold increase in titer during the spring and summer when mosquito exposure was likely to be the highest. During the first year of the study, the increase in titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of control subjects. This finding suggests that long-lasting permethrin-impregnated clothing provided protection against mosquito bites. PMID:26195460

  15. Long-lasting airplane headache in a patient with chronic rhinosinusitis.

    PubMed

    Pfund, Z; Trauninger, A; Szanyi, I; Illes, Z

    2010-04-01

    The authors report long-lasting airplane headache in a patient with non-allergic, chronic rhinosinusitis. Association of mucosal inflammation with compromised sinonasal ventilation and sinus barotrauma created a base for not only the pain but also for the prolongation of symptoms. Effective therapy with antihistamine and nasal decongestant supports the theory that sinonasal barotrauma plays a triggering role in the pathophysiology of airplane headache.

  16. Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting mechanical hypersensitivity.

    PubMed

    Martínez-Rojas, Vladimir A; García, Guadalupe; Noriega-Navarro, Roxana; Guzmán-Priego, Crystell G; Torres-López, Jorge E; Granados-Soto, Vinicio; Murbartián, Janet

    2018-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity. Formalin (1%)-induced chronic hypersensitivity was determined by the application of von Frey filaments to ipsilateral and contralateral paws and through pharmacological testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting. Formalin (1%) injection produced acute flinching behavior (1 h) as well as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment (10 min before) or posttreatment (6 days later) with A-967079 (1-100 µM) partially prevented and reversed, respectively, in a dose-dependent manner, long-lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin. Likewise, intrathecal pretreatment or posttreatment with A-967079 partially prevented and reversed, respectively, formalin-induced long-lasting hypersensitivity. A-967079 (100 µM) completely abolished the pro-nociceptive effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased TRPA1 protein expression in the DRG and spinal cord. Results indicate that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin-induced long-lasting secondary nociceptive hypersensitivity.

  17. Long-Lasting Neural and Behavioral Effects of Iron Deficiency in Infancy

    PubMed Central

    Lozoff, Betsy; Beard, John; Connor, James; Felt, Barbara; Georgieff, Michael; Schallert, Timothy

    2006-01-01

    Infants are at high risk for iron deficiency and iron-deficiency anemia. This review summarizes evidence of long-term effects of iron deficiency in infancy. Follow-up studies from preschool age to adolescence report poorer cognitive, motor, and social-emotional function, as well as persisting neurophysiologic differences. Research in animal models points to mechanisms for such long-lasting effects. Potential mechanisms relate to effects of iron deficiency during brain development on neurometabolism, myelination, and neurotransmitter function. PMID:16770951

  18. Long-lasting permethrin impregnated uniforms: A randomized-controlled trial for tick bite prevention.

    PubMed

    Vaughn, Meagan F; Funkhouser, Sheana Whelan; Lin, Feng-Chang; Fine, Jason; Juliano, Jonathan J; Apperson, Charles S; Meshnick, Steven R

    2014-05-01

    Because of frequent exposure to tick habitats, outdoor workers are at high risk for tick-borne diseases. Adherence to National Institute for Occupational Safety and Health-recommended tick bite prevention methods is poor. A factory-based method for permethrin impregnation of clothing that provides long-lasting insecticidal and repellent activity is commercially available, and studies are needed to assess the long-term effectiveness of this clothing under field conditions. To evaluate the protective effectiveness of long-lasting permethrin impregnated uniforms among a cohort of North Carolina outdoor workers. A double-blind RCT was conducted between March 2011 and September 2012. Subjects included outdoor workers from North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife who worked in eastern or central North Carolina. A total of 159 volunteer subjects were randomized, and 127 and 101 subjects completed the first and second years of follow-up, respectively. Uniforms of participants in the treatment group were factory-impregnated with long-lasting permethrin whereas control group uniforms received a sham treatment. Participants continued to engage in their usual tick bite prevention activities. Incidence of work-related tick bites reported on weekly tick bite logs. Study subjects reported 1,045 work-related tick bites over 5,251 person-weeks of follow-up. The mean number of reported tick bites in the year prior to enrollment was similar for both the treatment and control groups, but markedly different during the study period. In our analysis conducted in 2013, the effectiveness of long-lasting permethrin impregnated uniforms for the prevention of work-related tick bites was 0.82 (95% CI=0.66, 0.91) and 0.34 (95% CI=-0.67, 0.74) for the first and second years of follow-up. These results indicate that long-lasting permethrin impregnated uniforms are highly effective for at least 1 year in deterring tick bites in the context of typical tick bite

  19. Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances.

    PubMed

    Almeida, Roberto Farina de; Ganzella, Marcelo; Machado, Daniele Guilhermano; Loureiro, Samanta Oliveira; Leffa, Douglas; Quincozes-Santos, André; Pettenuzzo, Letícia Ferreira; Duarte, Marta Maria Medeiros Frescura; Duarte, Thiago; Souza, Diogo Onofre

    2017-06-02

    Major depressive disorder (MDD) is a neuropsychiatric disease that is associated with profound disturbances in affected individuals. Elucidating the pathophysiology of MDD has been frustratingly slow, especially concerning the neurochemical events and brain regions associated with disease progression. Thus, we evaluated the time-course (up to 8weeks) behavioral and biochemical effects in mice that underwent to a bilateral olfactory bulbectomy (OBX), which is used to modeling depressive-like behavior in rodents. Similar to the symptoms in patients with MDD, OBX induced long-lasting (e.g., impairment of habituation to novelty, hyperactivity and an anxiety-like phenotype) and transient (e.g., loss of self-care and motivational behavior) behavioral effects. Moreover, OBX temporarily impaired hippocampal synaptosomal mitochondria, in a manner that would be associated with hippocampal-related synaptotoxicity. Finally, long-lasting pro-oxidative (i.e., increased levels of reactive oxygen species and nitric oxide and decreased glutathione levels) and pro-inflammatory (i.e., increased levels of pro-inflammatory cytokines IL-1, IL-6, TNF-α and decreased anti-inflammatory cytokine IL-10 levels) effects were induced in the hippocampus by OBX. Additionally, these parameters were transiently affected in the posterior and frontal cortices. This study is the first to suggest that the transient and long-lasting behavioral effects from OBX strongly correlate with mitochondrial, oxidative and inflammatory parameters in the hippocampus; furthermore, these effects show a weak correlation with these parameters in the cortex. Our findings highlight the underlying mechanisms involved in the biochemical time course of events related to depressive behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The substrate for long-lasting memory: if not protein synthesis, then what?

    PubMed Central

    Routtenberg, Aryeh

    2011-01-01

    The prevailing textbook view that de novo protein synthesis is required for memory (e.g., Bear, 2006) is seriously flawed and the alternative hypothesis has been proposed in which post-translational modification (PTM) of proteins already synthesized and already present within the synapse is ‘the’ substrate for long-lasting memory (Routtenberg and Rekart, 2005). Protein synthesis serves a replenishment role. The first part of this review discusses how long-lasting memory can be achieved with ‘only’ PTM of existing synaptic proteins. The second part critically reviews a recent report published in Neuron 2007 that exemplifies the current view of protein synthesis and memory while also illustrating how these results can be understood within this new PTM framework. A necessary yet unexpected conclusion to emerge from consideration of the consequences of a PTM mechanism as the necessary, sufficient and exclusive substrate for long-lasting memory (Routtenberg and Rekart, 2005), is that the central Hebbian dogma that cells that ‘fire together, wire together’ is an unlikely mechanism for long-lasting memory. Thus, a unique feature of the PTM model is that longevity of information storage is achieved not by stability of the synaptic mechanism, but by impermanent pseudoredundant circuits. This is so because PTM is a reversible process and thus any permanent connection, any ‘lasting effect’ cannot be in the form of stable synapse formation. We have therefore proposed a solution in which network level processes regulate cellular mechanisms, even as such mechanisms regulate the network. Thus, synapses are ‘meta-stabilized’ by regulated feedback mediated by the circuit in which the synapse is embedded. For example, spontaneous activity is proposed to be a substrate feedback mechanism we term ‘cryptic rehearsal’ to sustain for some period of time after learning an approximation to the state initially created by input. Additionally, because the duplication

  1. miR-12 and miR-124 contribute to defined early phases of long-lasting and transient memory.

    PubMed

    Michely, Julia; Kraft, Susanne; Müller, Uli

    2017-08-11

    MicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in long-lasting synaptic plasticity and long-term memory (LTM). Since recent findings demonstrated a role of epigenetic regulation of gene expression in early memory phases we investigated whether epigenetic regulation by miRNAs also contributes to early memory phases. We used the olfactory associative learning paradigm in honeybees and addressed the contribution of miRNAs depending on the conditioning strength. We selected miR-12, miR-124, and miR-125 that have been implicated in processes of neuronal plasticity and analysed their contribution to non-associative and associative learning using miRNA inhibitors. Blocking miR-12, miR-124, or miR125 neither affects gustatory sensitivity nor habituation nor sensitization. Blocking the function of miR-12 and miR-124 during and shortly after 3-trial conditioning impairs different early memory phases. Although different, the function of miR-12 and miR-124 is also required for early phases of transient memory that is induced by 1-trial conditioning. Blocking miR-125 has no effect on early memory independent of the conditioning strength. These findings demonstrate that distinct miRNAs contribute to early phases of both, transient memories as well as long-lasting memories.

  2. Surface electromyographic assessment of patients with long lasting temporomandibular joint disorder pain.

    PubMed

    Tartaglia, Gianluca M; Lodetti, Gianluigi; Paiva, Guiovaldo; De Felicio, Claudia Maria; Sforza, Chiarella

    2011-08-01

    The normalized electromyographic characteristics of masticatory muscles in patients with temporomandibular joint disorders (TMD) and healthy controls were compared. Thirty TMD patients (15 men, 15 women, mean age 23 years) with long lasting pain (more than 6 months), and 20 control subjects matched for sex and age were examined. All patients had arthrogenous TMD according to the Research Diagnostic Criteria for TMD (RDC/TMD). Surface electromyography of masseter and temporal muscles was performed during maximum teeth clenching either on cotton rolls or in intercuspal position. Standardized EMG indices and the median power frequency were obtained, and compared between the two groups and sexes using ANOVAs. During clenching, the TMD patients had larger asymmetry in their temporalis muscles, larger temporalis activity relative to masseter, and reduced mean power frequencies than the control subjects (p<0.05, ANOVA). In both groups, the mean power frequencies of the temporalis muscles were larger than those of the masseter muscles (p<0.001). No sex related differences, and no sex × group interactions were found. In conclusion, young adult patients with long lasting TMD have an increased and more asymmetric standardized activity of their temporalis anterior muscle, and reduced mean power frequencies, relative to healthy controls. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. [Effects of chronic buspirone treatment on female mice exposed to the long-lasting psychoemotional influence].

    PubMed

    Avgustinovich, D F; Vishnevetskaia, G B

    2011-02-01

    The effects of chronic treatment (30 days) with the 5-HT1A receptor partial agonist buspirone (0.05, 1 and 10 mg/kg i.p.) on the behaviour of C57BL/6J female mice exposed to long-lasting psychoemotional influence were studied. The influence involved forced living of each female with an aggressive male separated with a perforated transparent partition in the same cage and daily female's presence during 10-min intermale confrontations behind a partition caused by introducing of another male to the aggressive male. Chronic buspirone injection (in all used doses) did not affect the behaviour of females estimated in the "partitions" and "open field" tests at the end of the drug treatment. The anxiolytic effect of buspirone only at the dose of 1 mg/kg on the female's plus-maze behaviour was revealed. In the Porsolt, test buspirone in the dose of 1 mg/kg caused a slight increase in the duration of immobility indicating a slight pro-depressive effect. Thus, chronic buspirone treatment of females exposed to the long-lasting psychoemotional impact has a different effect on their behaviour depending on the dose and test conditions.

  4. Long-lasting semantic interference effects in object naming are not necessarily conceptually mediated

    PubMed Central

    Riley, Emma; McMahon, Katie L.; de Zubicaray, Greig

    2015-01-01

    Long-lasting interference effects in picture naming are induced when objects are presented in categorically related contexts in both continuous and blocked cyclic paradigms. Less consistent context effects have been reported when the task is changed to semantic classification. Experiment 1 confirmed the recent finding of cumulative facilitation in the continuous paradigm with living/non-living superordinate categorization. To avoid a potential confound involving participants responding with the identical superordinate category in related contexts in the blocked cyclic paradigm, we devised a novel set of categorically related objects that also varied in terms of relative age – a core semantic type associated with the adjective word class across languages. Experiment 2 demonstrated the typical interference effect with these stimuli in basic level naming. In Experiment 3, using the identical blocked cyclic paradigm, we failed to observe semantic context effects when the same pictures were classified as younger–older. Overall, the results indicate the semantic context effects in the two paradigms do not share a common origin, with the effect in the continuous paradigm arising at the level of conceptual representations or in conceptual-to-lexical connections while the effect in the blocked cyclic paradigm most likely originates at a lexical level of representation. The implications of these findings for current accounts of long-lasting interference effects in spoken word production are discussed. PMID:25999892

  5. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors.

    PubMed

    Bales, K L; Plotsky, P M; Young, L J; Lim, M M; Grotte, N; Ferrer, E; Carter, C S

    2007-01-05

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations.

  6. Glutamine triggers long-lasting increase in striatal network activity in vitro.

    PubMed

    Fleischer, Wiebke; Theiss, Stephan; Schnitzler, Alfons; Sergeeva, Olga

    2017-04-01

    Accumulation of ammonium and glutamine in blood and brain is a key factor in hepatic encephalopathy (HE) - a neuropsychiatric syndrome characterized by various cognitive and motor deficits. MRI imaging identified abnormalities notably in the basal ganglia of HE patients, including its major input station, the striatum. While neurotoxic effects of ammonia have been extensively studied, glutamine is primarily perceived as "detoxified" form of ammonia. We applied ammonium and glutamine to striatal and cortical cells from newborn rats cultured on microelectrode arrays. Glutamine, but not ammonium significantly increased spontaneous spike rate with a long-lasting excitation outlasting washout. This effect was more prominent in striatal than in cortical cultures. Calcium imaging revealed that glutamine application caused a rise in intracellular calcium that depended both on system A amino acid transport and activation of ionotropic glutamate receptors. This pointed to downstream glutamate release that was triggered by intracellular glutamine. Using an enzymatic assay kit we confirmed glutamine-provoked glutamate release from striatal cells. Real-time PCR and immunocytochemistry demonstrated the presence of vesicular glutamate transporters (VGLUT1 and VGLUT2) necessary for synaptic glutamate release in striatal neurons. We conclude that extracellular glutamine is taken up by neurons, triggers synaptic release of glutamate which is then taken up by astrocytes and again converted to glutamine. This feedback-loop causes a sustained long-lasting excitation of network activity. Thus, apart from ammonia also its "detoxified" form glutamine might be responsible for the neuropsychiatric symptoms in HE. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Control of Culicoides sonorensis (Diptera: Ceratopogonidae) blood feeding on sheep with long-lasting repellent pesticides.

    PubMed

    Reeves, W K; Lloyd, J E; Stobart, R; Stith, C; Miller, M M; Bennett, K E; Johnson, G

    2010-09-01

    Culicoides sonorensis is the primary vector of bluetongue and epizootic hemorrhagic disease viruses in North America. Bluetongue disease is one of the most economically important arthropod-borne diseases of sheep in North America, because it causes significant morbidity and mortality and can lead to local quarantines and international trade restrictions. Long-lasting repellent pesticides could be applied to sheep as they are moved down from mountain pastures to protect them from biting midges until the 1st frost. We tested long-lasting pesticides on sheep as repellents against C. sonorensis. Both Python ear tags with 10% zeta-cypermethrin (9.8 g/tag) synergized with 20% piperonyl butoxide (PBO) and a 12-ml low-volume spray application of ready-to-use sheep insecticide (Y-TEX) with 2.5% permethrin and 2.5% PBO in an oil-based formulation were repellent to C. sonorensis for at least 3-5 wk after a single application.

  8. [Understanding the non-use of long-lasting impregnated nets (LLINs) in Niger].

    PubMed

    Faye, S L

    2012-01-01

    In Niger, malaria is the leading cause of mortality and morbidity among pregnant women and children under 5 years. To decrease these rates, the country initiated a prevention policy of free distribution of long-lasting impregnated nets (LLINs). However, improved physical access to this preventive tool has not led to its regular use in households. A nationally representative quantitative and qualitative survey sought to document the reasons for non-use. The results show that the possession of a LLIN is quite low and confirm the low utilization rate, with significant differences by region. Cultural beliefs are not the main barriers to the use of LLINs in Niger. Knowledge and social, technical, environmental and economic dimensions were all more decisive. These results suggest that while improving awareness and communication is important for changing behavior, it cannot alone remove certain socioeconomic barriers and improve LLIN use.

  9. Trials of Improved Practices (TIPs): A Strategy for Making Long-Lasting Nets Last Longer?

    PubMed Central

    Harvey, Steven A.; Paredes Olórtegui, Maribel; Leontsini, Elli; Ramal Asayag, César; Scott, Kerry; Winch, Peter J.

    2013-01-01

    Long-lasting insecticidal net (LLIN) use is a proven malaria prevention method. Mass distribution has greatly expanded LLIN access in sub-Saharan Africa, but a gap remains between LLIN ownership and use. Furthermore, LLINs wear out more quickly than anticipated. This paper suggests a participatory research strategy—trials of improved practices (TIPs)—that could identify locally appropriate approaches to prolonging net life and increasing effective use. We used TIPs to overcome barriers to optimal net use in the Peruvian Amazon. Working with 15 families in three villages, we tested home treatment of cotton nets, use of an alternative netting fabric, and alternative washing and care instructions. TIPs helped confirm feasibility of these interventions. Although our findings are time- and context-specific, TIPs could help improve consistency and effectiveness of current LLIN use and prolong net lifespan in sub-Saharan Africa and elsewhere. This would help maximize the value of shrinking donor resources for malaria. PMID:23530074

  10. Pregnancy leads to long-lasting changes in human brain structure.

    PubMed

    Hoekzema, Elseline; Barba-Müller, Erika; Pozzobon, Cristina; Picado, Marisol; Lucco, Florencio; García-García, David; Soliva, Juan Carlos; Tobeña, Adolf; Desco, Manuel; Crone, Eveline A; Ballesteros, Agustín; Carmona, Susanna; Vilarroya, Oscar

    2017-02-01

    Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective ('pre'-'post' pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not in-between sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women's babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestive of an adaptive process serving the transition into motherhood. Another follow-up session showed that the GM reductions endured for at least 2 years post-pregnancy. Our data provide the first evidence that pregnancy confers long-lasting changes in a woman's brain.

  11. An unusually long-lasting outbreak of community-acquired Legionnaires' disease, 2005-2008, Italy.

    PubMed

    Scaturro, M; Fontana, S; Crippa, S; Caporali, M G; Seyler, T; Veschetti, E; Villa, G; Rota, M C; Ricci, M L

    2015-08-01

    An unusually long-lasting community-acquired outbreak of Legionnaires' disease (LD) occurred in the inhabitants of a town in northern Italy from 2005 to 2008. Overall, 43 cases were diagnosed including five deaths. Hundreds of water samples were collected for Legionella isolation but only two clinical samples were obtained. Clinical strains were ST23 as were environmental isolates detected in most Legionella-positive patients' homes and those from a public fountain. Although no Legionella was found in the municipal water mains, a continuous chlorination was applied in 2008. This action resulted in a halving of cases, although incidence remained tenfold higher than the Italian average incidence until the end of 2013, when it dropped to the expected rate. Retrospective analyses of prevalent wind direction suggested that a hidden cooling tower could have been the main cause of this uncommon outbreak, highlighting the importance of implementation of cooling tower registers in supporting LD investigations.

  12. Long lasting cadmium intake is associated with reduction of insulin receptors in rat adipocytes.

    PubMed

    Ficková, M; Eybl, V; Kotyzová, D; Micková, V; Möstbök, S; Brtko, J

    2003-12-01

    The effects of chronic cadmium exposure on adipose tissue have not been extensively reported. In adult Wistar male rats we investigated in vivo effect of 6 weeks lasting cadmium intake in drinking tap water (CdCl2 9,7 mg/l). Insulin receptors in isolated adipocytes from epididymal fat and glucose transporter protein GLUT4 content in fat tissue plasma membranes were determined. Control and Cd treated rats had similar water intake with subsequent heavy augmentation of Cd content in liver of experimental animals. In comparison with controls, Cd intake did not influence body mass increment and fat cell size, but significantly increased serum glycemia and moderately elevated insulinemia. Cadmium intake significantly reduced (approximately 50%) both, total insulin receptors number and density of the receptors in fat cells. No differences in the content of GLUT4 in crude plasma membranes of adipose tissue were observed. Diminished insulin receptors in adipocytes could account for diabetogenic effect of long lasting cadmium intake.

  13. Electronic signatures for long-lasting storage purposes in electronic archives.

    PubMed

    Pharow, Peter; Blöbel, Bernd

    2003-01-01

    Communication and co-operation in healthcare and welfare requires certain Trusted Third Party (TTP) services describing both status and relation of communicating principals as well as their corresponding keys and attributes. Additional TTP services are needed to provide trustworthy information about dynamic issues of communication and co-operation such as time and location of processes, workflow relations, and system behaviour. Electronic signatures based on asymmetric cryptography are important means for securing the integrity of a message or file as well as for accountability purposes including non-repudication of both origin and receipt. These electronic signatures along with certified time stamps are especially important for electronic health records (EHR), electronic archives in general, and other typical purposes of a long-lasting storage. Apart from technical storage problems (e.g. lifetime of the storage devices), this paper needs to look for mechanisms of e.g. re-signing of messages, archive details, or whole archives.

  14. Human dignity as a component of a long-lasting and widespread conceptual construct.

    PubMed

    Baertschi, Bernard

    2014-06-01

    For some decades, the concept of human dignity has been widely discussed in bioethical literature. Some authors think that this concept is central to questions of respect for human beings, whereas others are very critical of it. It should be noted that, in these debates, dignity is one component of a long-lasting and widespread conceptual construct used to support a stance on the ethical question of the moral status of an action or being. This construct has been used from Modernity onward to condemn slavery and torture as violations of human dignity. In spelling it out, we can come to a better understanding of what "dignity" means and become aware that there exists a quite useful place for this notion in our ethical thought, albeit a modest one.

  15. An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.

    PubMed

    Della Valle, M; Chincarini, G; Panagia, N; Tagliaferri, G; Malesani, D; Testa, V; Fugazza, D; Campana, S; Covino, S; Mangano, V; Antonelli, L A; D'Avanzo, P; Hurley, K; Mirabel, I F; Pellizza, L J; Piranomonte, S; Stella, L

    2006-12-21

    Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from the distant Universe. Long-duration GRBs (those lasting more than approximately 2 s) are believed to originate from the deaths of massive stars, mainly on the basis of a handful of solid associations between GRBs and supernovae. GRB 060614, one of the closest GRBs discovered, consisted of a 5-s hard spike followed by softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here we report deep optical observations of GRB 060614 showing no emerging supernova with absolute visual magnitude brighter than M(V) = -13.7. Any supernova associated with GRB 060614 was therefore at least 100 times fainter, at optical wavelengths, than the other supernovae associated with GRBs. This demonstrates that some long-lasting GRBs can either be associated with a very faint supernova or produced by different phenomena.

  16. Laboratory evaluation of rubidium as a long-lasting marker for bloodfeeding sand flies (Diptera: Psychodidae).

    PubMed

    Mascari, T M; Stout, R W; Foil, L D

    2012-01-01

    The objective of this study was to evaluate the use of the trace element rubidium (Rb) as a long-lasting systemic biomarker for bloodfeeding females of the sand fly Phlebotomus papatasi Scopoli. Baits containing Rb chloride were found to be palatable to hamsters in this study. We were able to detect Rb using a portable X-ray fluorescence analyzer in all sand flies that fed on Rb-treated hamsters for at least 14 d postbloodmeal. We also detected Rb in sand flies that took a bloodmeal from hamsters up to 10 d after the hamsters were withdrawn from a Rb-treated diet. Results of this study constitute proof of concept for the incorporation of Rb chloride into rodent baits for marking bloodfeeding sand flies, and suggest that Rb marking could be used as a technique for evaluating rodent-targeted sand fly control methods and in ecological studies on sand flies.

  17. Safety and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia.

    PubMed

    Bláha, Milan; Cermanová, Melanie; Bláha, Vladimír; Blazek, Martin; Malý, Jaroslav; Siroký, Oldrich; Solichová, Dagmar; Filip, Stanislav; Rehácek, Vít

    2007-02-01

    The aim of this work is to arbitrate the incidence of side effects and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia. 1200 procedures were performed and the last 463 of them were evaluated. An immunoadsorption method of LDL-apheresis was used (continuous blood cell separator Cobe Spectra; secondary device: automated adsorption-desorption ADA, Medicap; absorption columns: Lipopak). As a whole, 6.26% adverse events were found and subsequently resolved by standard symptomatic therapy. Vaso-vagal reactions (symptoms of neurovegetative lability) were the most common adverse effects, presented as malaise, weakness, slight and short-term drop in blood pressure or other general signs. They were all well controlled by symptomatic therapy. We conclude that LDL-apheresis in the hands of experienced personnel is a safe procedure. An acceptable procedure duration limit, balancing the possibility to achieve a targeted cholesterol level while still maintaining an acceptable patient tolerance, was confirmed to be 4 hours.

  18. Proton Auroral Emissions without Electron Auroral Emissions in Long-lasting Complex Substorms

    NASA Astrophysics Data System (ADS)

    Bryant, C. R.; Murphree, J. S.; Mende, S.

    2008-12-01

    The SI-12 and WIC FUV instruments aboard the IMAGE satellite provide a unique ability to compare LBH and proton auroral emissions. The auroral power allows for the examination of the relationship of proton and electron emissions. In the past, measurements in the LBH band have been used to identify substorms. There are, however, cases where there is significant proton auroral emission while there is little to no electron emission in the LBH band. During intense, long-lasting complex substorms it is possible that while the WIC images show a decreasing intensity and entry into a more recovered state. At the same time, images from the SI-12 camera show increased intensities and possibly further substorms seen only in the proton emissions. An example of this can be seen in the events of November 15, 2001 from 1700-2200 UT. An investigation of this event will be presented and possible explanations of these events will be put forth.

  19. Niacinamide leave-on formulation provides long-lasting protection against bacteria in vivo.

    PubMed

    Mathapathi, Mruthyunjaya Swamy; Mallemalla, Prathyusha; Vora, Shilpa; Iyer, Vidula; Tiwari, Jyoti Kumar; Chakrabortty, Amit; Majumdar, Amitabha

    2017-09-01

    Antimicrobial peptides (AMPs) form a part of the skin's innate immune system. Their primary activity is to provide antimicrobial benefits and hence protect from infections. AMPs that are present on human skin include psoriasin (S100A7), RNase 7, lysozyme, LL-37 and defensins. Niacinamide is a well-known cosmetic ingredient that has been used traditionally for multiple skin benefits. Recent data indicate that niacinamide treatment can boost AMPs in human gut epithelial cells and in neutrophils. Treatment with niacinamide in mice also provided protection from skin infections by enhancing AMPs. In this article, we find that treatment with niacinamide formulation provides long-lasting protection against bacteria, potentially through the activation of an AMP response. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Passive sensorimotor stimulation triggers long lasting alpha-band fluctuations in visual perception.

    PubMed

    Tomassini, Alice; D'Ausilio, Alessandro

    2018-02-01

    Movement planning and execution rely on the anticipation and online control of the incoming sensory input. Evidence suggests that sensorimotor processes may synchronize visual rhythmic activity in preparation of action performance. Indeed, we recently reported periodic fluctuations of visual contrast sensitivity that are time-locked to the onset of an intended movement of the arm. However, the origin of the observed visual modulations has so far remained unclear because of the endogenous (and thus temporally undetermined) activation of the sensorimotor system that is associated with voluntary movement initiation. In this study, we activated the sensorimotor circuitry involved in the hand control in an exogenous and controlled way by means of peripheral stimulation of the median nerve and characterized the spectrotemporal dynamics of the ensuing visual perception. The stimulation of the median nerve triggers robust and long-lasting (∼1 s) alpha-band oscillations in visual perception, whose strength is temporally modulated in a way that is consistent with the changes in alpha power described at the neurophysiological level after sensorimotor stimulation. These findings provide evidence in support of a causal role of the sensorimotor system in modulating oscillatory activity in visual areas with consequences for visual perception. NEW & NOTEWORTHY This study shows that the peripheral activation of the somatomotor hand system triggers long-lasting alpha periodicity in visual perception. This demonstrates that not only the endogenous sensorimotor processes involved in movement preparation but also the passive stimulation of the sensorimotor system can synchronize visual activity. The present work suggests that oscillation-based mechanisms may subserve core (task independent) sensorimotor integration functions.

  1. Neonatal Oxytocin Manipulations Have Long-Lasting, Sexually Dimorphic Effects on Vasopressin Receptors

    PubMed Central

    Bales, Karen L.; Plotsky, Paul M.; Young, Larry J.; Lim, Miranda M.; Grotte, Nathaniel; Ferrer, E.; Carter, C. Sue

    2007-01-01

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations. PMID:17055176

  2. Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation

    PubMed Central

    Toprani, Sheela; Durand, Dominique M

    2013-01-01

    Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease. Deep brain electrical stimulation (DBS) of grey matter has been used for MTLE with limited success. However, stimulation of a white matter tract connecting the hippocampi, the ventral hippocampal commissure (VHC), with low frequencies that simulate interictal discharges has shown promising results, with seizure reduction greater than 98% in bilateral hippocampi during stimulation and greater than 50% seizure reduction in bilateral hippocampi after treatment. A major hurdle to the implementation and optimization of this treatment is that the mechanisms of seizure reduction by low frequency electrical stimulation (LFS) are not known. The goal of this study is to understand how commissural fibre tract stimulation reduces bilateral hippocampal epileptic activity in an in vitro slice preparation containing bilateral hippocampi connected by the VHC. It is our hypothesis that electrical stimuli induce hyperpolarization lasting hundreds of milliseconds following each pulse which reduces spontaneous epileptic activity during each inter-stimulus interval (ISI). Stimulus-induced long-lasting-hyperpolarization (LLH) can be mediated by GABAB inhibitory post-synaptic potentials (IPSPs) or slow after-hyperpolarization (sAHP). To test the role of LLH in effective bilateral seizure reduction by fibre tract stimulation, we measured stimulus-induced hyperpolarization during LFS of the VHC using electrophysiology techniques. Antagonism of the GABAB IPSP and/or sAHP diminished stimulus-induced hyperpolarization concurrently with LFS efficacy (greater than 50% reduction). Blocking both the GABAB IPSP and sAHP simultaneously eliminated the effect of electrical stimulation on seizure reduction entirely. These data show that LFS of the VHC is an effective protocol for bilateral hippocampal seizure reduction and that its efficacy relies on the induction of long-lasting hyperpolarization mediated

  3. Acetylcholine encodes long-lasting presynaptic plasticity at glutamatergic synapses in the dorsal striatum after repeated amphetamine exposure.

    PubMed

    Wang, Wengang; Darvas, Martin; Storey, Granville P; Bamford, Ian J; Gibbs, Jeffrey T; Palmiter, Richard D; Bamford, Nigel S

    2013-06-19

    Locomotion and cue-dependent behaviors are modified through corticostriatal signaling whereby short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders, including Parkinson's disease and drug dependence. We found that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted >50 d in treated mice. An amphetamine challenge reversed CPD via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons. This PPP was correlated with locomotor responses after a drug challenge, suggesting that it may underlie the sensitization process. Experiments in brain slices and in vivo indicated that dopamine regulation of acetylcholine release from tonically active interneurons contributes to CPD, PPP, locomotor sensitization, and cognitive ability. Therefore, a chronic decrease in corticostriatal activity during withdrawal is regulated around a new physiological range by tonically active interneurons and returns to normal upon reexposure to amphetamine, suggesting that this paradoxical return of striatal activity to a more stable, normalized state may represent an additional source of drug motivation during abstinence.

  4. Acetylcholine Encodes Long-Lasting Presynaptic Plasticity at Glutamatergic Synapses in the Dorsal Striatum after Repeated Amphetamine Exposure

    PubMed Central

    Wang, Wengang; Darvas, Martin; Storey, Granville P.; Bamford, Ian J.; Gibbs, Jeffrey T.; Palmiter, Richard D.

    2013-01-01

    Locomotion and cue-dependent behaviors are modified through corticostriatal signaling whereby short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders, including Parkinson's disease and drug dependence. We found that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted >50 d in treated mice. An amphetamine challenge reversed CPD via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons. This PPP was correlated with locomotor responses after a drug challenge, suggesting that it may underlie the sensitization process. Experiments in brain slices and in vivo indicated that dopamine regulation of acetylcholine release from tonically active interneurons contributes to CPD, PPP, locomotor sensitization, and cognitive ability. Therefore, a chronic decrease in corticostriatal activity during withdrawal is regulated around a new physiological range by tonically active interneurons and returns to normal upon reexposure to amphetamine, suggesting that this paradoxical return of striatal activity to a more stable, normalized state may represent an additional source of drug motivation during abstinence. PMID:23785153

  5. Sleep Deprivation During Early-Adult Development Results in Long-Lasting Learning Deficits in Adult Drosophila

    PubMed Central

    Seugnet, Laurent; Suzuki, Yasuko; Donlea, Jeff M.; Gottschalk, Laura; Shaw, Paul J.

    2011-01-01

    long-lasting learning deficits in adult drosophila. SLEEP 2011;34(2):137-146. PMID:21286249

  6. [Effects of preparation parameters on the long lasting luminescence of ZnGa2O4].

    PubMed

    Huang, Shang-yong; Zhang, Xi-qing; Huang, Hai-qin; Yao, Zhi-gang

    2008-12-01

    Using high temperature solid state reaction method, ZnO and Ga2O3 with high purity as raw materials, different ZnGa2O4 samples were prepared at different molar ratios of raw materials and different temperatures. After excitation of the ZnGa2O4 samples by 254 nm UV lamps, obvious long lasting luminescence was detected for the first time, which showed two new long lasting luminescence peaks at 505 nm and 690 nm, respectively. And the relative intensity of the two peaks was effected by the preparation conditions such as molar ratio of the two raw materials and the sintering temperature. Less ZnO or higher temperature will strengthen the relative intensity of the 505 nm peak, while more ZnO or lower temperature will strengthen the relative intensity of the 690 nm peak. The origin of the two peaks was discussed based on some corresponding documents, and the conclusion is that the 505 nm peak comes from the 2E(A)-->4A2 transition of Ga3+ in a relatively distorted octahedral after some Zn2+ are substituted by Ga3+; and the 690 nm peak comes from the V0*--O2- transition after the singly charged ion oxygen vacancies appeare in the octahedral structure. The reasons why the preparing conditions can affect the relative peak intensity of the two peaks were also discussed. Less ZnO will cause Zn2O vacancies in the structure and more Ga3+ will occupy the Zn2+ positions, then will form distorted octahedral, and then the transition from energy level 2E(A) to (4)A2 of Ga3+ will cause the 505 nm peak to be dominant. On the other hand. too much ZnO will form oxygen vacancies, which will cause the 690 nm peak to be dominant. Higher temperature will cause more evaporation of ZnO and then relative less ZnO, and lower temperature will cause less evaporation of ZnO and then more oxygen vacancies. These conclusions are corresponding with the origin of the two peaks discussed before.

  7. Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

    SciTech Connect

    Lundstedt, Dan; Gustafsson, Magnus; Steineck, Gunnar; Malmstroem, Per; Alsadius, David; Sundberg, Agnetha; Wilderaeng, Ulrica; Holmberg, Erik; Johansson, Karl-Axel; Karlsson, Per

    2012-05-01

    Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting

  8. Use and acceptance of long lasting insecticidal net screens for dengue prevention in Acapulco, Guerrero, Mexico.

    PubMed

    Jones, Catrin H; Benítez-Valladares, David; Guillermo-May, Guillermo; Dzul-Manzanilla, Felipe; Che-Mendoza, Azael; Barrera-Pérez, Mario; Selem-Salas, Celia; Chablé-Santos, Juan; Sommerfeld, Johannes; Kroeger, Axel; O'Dempsey, Timothy; Medina-Barreiro, Anuar; Manrique-Saide, Pablo

    2014-08-14

    Dengue, recognized by the WHO as the most important mosquito-borne viral disease in the world, is a growing problem. Currently, the only effective way of preventing dengue is vector control. Standard methods have shown limited effect, and there have been calls to develop new integrated vector management approaches. One novel tool, protecting houses with long lasting insecticidal screens on doors and windows, is being trialled in a cluster randomised controlled trial by a joint UADY/WHO TDR/IDRC study in various districts of Acapulco, Mexico, with exceptionally high levels of crime and insecurity.This study investigated the community's perspectives of long lasting insecticidal screens on doors and windows in homes and in schools, in order to ascertain their acceptability, to identify challenges to further implementation and opportunities for future improvements. This was a sequential mixed-methods study. The quantitative arm contained a satisfaction survey administered to 288 houses that had received the intervention examining their perspectives of both the intervention and dengue prevention in general. The qualitative arm consisted of Focus Group Discussions (FGDs) with those who had accepted the intervention and key informant interviews with: schoolteachers to discuss the use of the screens in schools, program staff, and community members who had refused the intervention. Overall satisfaction and acceptance of the screens was very high, with only some operational and technical complaints relating to screen fragility and the installation process. However, the wider social context of urban violence and insecurity was a major barrier to screen acceptance. Lack of information dissemination and community collaboration were identified as project weaknesses. The screens are widely accepted by the population, but the project implementation could be improved by reassuring the community of its legitimacy in the context of insecurity. More community engagement and better

  9. Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

    SciTech Connect

    Lundstedt, Dan, E-mail: dan.lundstedt@vgregion.se; Department of Oncology, Sahlgrenska University Hospital, Gothenburg; Gustafsson, Magnus

    2012-05-01

    Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastasesmore » had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting

  10. Environmental enrichment of young adult rats (Rattus norvegicus) in different sensory modalities has long-lasting effects on their ability to learn via specific sensory channels.

    PubMed

    Dolivo, Vassilissa; Taborsky, Michael

    2017-05-01

    Sensory modalities individuals use to obtain information from the environment differ among conspecifics. The relative contributions of genetic divergence and environmental plasticity to this variance remain yet unclear. Numerous studies have shown that specific sensory enrichments or impoverishments at the postnatal stage can shape neural development, with potential lifelong effects. For species capable of adjusting to novel environments, specific sensory stimulation at a later life stage could also induce specific long-lasting behavioral effects. To test this possibility, we enriched young adult Norway rats with either visual, auditory, or olfactory cues. Four to 8 months after the enrichment period we tested each rat for their learning ability in 3 two-choice discrimination tasks, involving either visual, auditory, or olfactory stimulus discrimination, in a full factorial design. No sensory modality was more relevant than others for the proposed task per se, but rats performed better when tested in the modality for which they had been enriched. This shows that specific environmental conditions encountered during early adulthood have specific long-lasting effects on the learning abilities of rats. Furthermore, we disentangled the relative contributions of genetic and environmental causes of the response. The reaction norms of learning abilities in relation to the stimulus modality did not differ between families, so interindividual divergence was mainly driven by environmental rather than genetic factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Enhanced Reality Showing Long-Lasting Analgesia after Total Knee Arthroplasty: Prospective, Randomized Clinical Trial.

    PubMed

    Koo, Kyo-In; Park, Dae Kwon; Youm, Yoon Seok; Cho, Sung Do; Hwang, Chang Ho

    2018-02-05

    To overcome the limitation of short-term efficacy of virtual reality (VR), an enhanced reality (ER) analgesia, (combination of the VR, real-time motion capture, mirror therapy [MT]) involving a high degree of patients' presence or embodiment was explored. Patients, who underwent unilateral total knee arthroplasty (TKA), received ER analgesia. The duration was 5 times a week, for 2 weeks for one group and 5 times a week, for 1 week in the other. Visual Analogue Scale (VAS) at rest and during movement, active knee range of motion (ROM) for flexion and extension were measured repeatedly. After screening 157 patients, 60 were included. Pre-interventional evaluation was performed at 6.7 days and ER was initiated at 12.4 days after surgery. Evaluation was performed at 5, 12, 33 days after the initiation of ER. Analgesia in the 2 week therapy group was effective until the third evaluation (p = 0.000), whereas in the other group, it was effective only until the second evaluation (p = 0.010). Improvement in ROM in the 2 week group was also maintained until the third evaluation (p = 0.037, p = 0.009). It could lay the foundations for the development of safe and long-lasting analgesic tools.

  12. Evaluation of New Tools for Malaria Vector Control in Cameroon: Focus on Long Lasting Insecticidal Nets

    PubMed Central

    Etang, Josiane; Nwane, Philippe; Piameu, Michael; Manga, Blaise; Souop, Daniel; Awono-Ambene, Parfait

    2013-01-01

    Background From 2006 to 2011, biological activity of insecticides for Indoor Residual Spraying (IRS), conventional treatment of nets (CTNs) or long lasting insecticidal nets (LLINs) was evaluated before their approval in Cameroon. The objective of the study was to select the best tools for universal malaria vector control coverage. Methodology Bioassays were performed using WHO cones and the Kisumu susceptible strain of Anopheles gambiae s.s.. Among tested products, residual activity and wash resistance of Alpha-cypermethrin LLINs (Interceptor) and CTNs (Fendona) were assessed during 5 months in the Ntougou neighborhood. Principal Findings All the 14 tested products were found effective (95–100% knockdown and mortality rates), although a significant decrease of efficacy was seen with lambda-cyhalothrinWP IRS, alpha-cypermethrin CTNs and LLINs (p< 0.05). However, the efficacy of Interceptor nets did not decrease during the 5 months evaluation, even after 25 washes (0.07

  13. Long-Lasting Cranial Nerve III Palsy as a Presenting Feature of Chronic Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Spataro, Rossella; La Bella, Vincenzo

    2015-01-01

    We describe a patient with chronic inflammatory demyelinating polyneuropathy (CIDP) in which an adduction deficit and ptosis in the left eye presented several years before the polyneuropathy. A 52-year-old man presented with a 14-year history of unremitting diplopia, adduction deficit, and ptosis in the left eye. At the age of 45 a mild bilateral foot drop and impaired sensation in the four limbs appeared, with these symptoms showing a progressive course. The diagnostic workup included EMG/ENG which demonstrated reduced conduction velocity with bilateral and symmetrical sensory and motor involvement. Cerebrospinal fluid studies revealed a cytoalbuminologic dissociation. A prolonged treatment with corticosteroids allowed a significant improvement of the limb weakness. Diplopia and ptosis remained unchanged. This unusual form of CIDP presented as a long-lasting isolated cranial nerve palsy. A diagnostic workup for CIDP should therefore be performed in those patients in which an isolated and unremitting cranial nerve palsy cannot be explained by common causes. PMID:25960744

  14. Early GRB Afterglows from Reverse Shocks in Ultra-relativistic, Long-lasting Winds

    NASA Astrophysics Data System (ADS)

    Lyutikov, Maxim; Camilo Jaramillo, Juan

    2017-02-01

    We develop a model of early Gamma-Ray Burst (GRB) afterglows with dominant X-ray contribution from the reverse shock (RS) propagating in highly relativistic (Lorentz factor γw ˜ 106) magnetized wind of a long-lasting central engine. The model reproduces, in a fairly natural way, the overall trends and yet allows for variations in the temporal and spectral evolution of early optical and X-ray afterglows. The high energy and the optical synchrotron emission from the RS particles occurs in the fast cooling regime; the resulting synchrotron power Ls is a large fraction of the wind luminosity, {L}s≈ {L}w/\\sqrt{1+{σ }w} (Lw and σw are wind power and magnetization). Thus, plateaus—parts of afterglow light curves that show slowly decreasing spectral power—are a natural consequence of the RS emission. Contribution from the forward shock (FS) is negligible in the X-rays, but in the optical both FS and RS contribute similarly: FS optical emission is in the slow cooling regime, producing smooth components, while RS optical emission is in the fast cooling regime, and thus can both produce optical plateaus and account for fast optical variability correlated with the X-rays, e.g., due to changes in the wind properties. We discuss how the RS emission in the X-rays and combined FS and RS emission in the optical can explain many puzzling properties of early GRB afterglows.

  15. Electronic signatures for long-lasting storage purposes in electronic archives.

    PubMed

    Pharow, Peter; Blobel, Bernd

    2005-03-01

    Communication and co-operation in healthcare and welfare require a certain set of trusted third party (TTP) services describing both status and relation of communicating principals as well as their corresponding keys and attributes. Additional TTP services are needed to provide trustworthy information about dynamic issues of communication and co-operation such as time and location of processes, workflow relations, and system behaviour. Legal and ethical requirements demand securely stored patient information and well-defined access rights. Among others, electronic signatures based on asymmetric cryptography are important means for securing the integrity of a message or file as well as for accountability purposes including non-repudiation of both origin and receipt. Electronic signatures along with certified time stamps or time signatures are especially important for electronic archives in general, electronic health records (EHR) in particular, and especially for typical purposes of long-lasting storage. Apart from technical storage problems (e.g. lifetime of the storage devices, interoperability of retrieval and presentation software), this paper identifies mechanisms of e.g. re-signing and re-stamping of data items, files, messages, sets of archived items or documents, archive structures, and even whole archives.

  16. Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone

    SciTech Connect

    Pang, P.K.T.; Wang, R.; Shan, J.; Karpinski, E.; Benishin, C.G. )

    1990-01-01

    The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.

  17. Origin and development of a scientific collaboration and a long-lasting friendship.

    PubMed

    Luzzati, A L

    2005-07-01

    The aim of this contribution is twofold: to honour Ivan Lefkovits with a short recollection of our scientific collaboration in the years 1972-1985 and a summary of our joint contribution to studies of the mechanisms and functions of the immune system and to acknowledge our long-lasting friendship. Ivan's limiting dilution microculture method was adapted to rabbit peripheral blood lymphocytes (PBL). The antibody produced in the responding cultures was shown to be electrophoretically homogeneous and, in rabbits heterozygous at the b locus, to express either one or the other allele. Thus, the antibody released in single microcultures was indeed the product of single B-cell clones and allelic exclusion, once achieved, was maintained throughout clonal proliferation. In the response to streptococcal polysaccharides, analysis of the clonotypes triggered in vitro provided information on mechanisms of clonal dominance. A two-stage culture system was established, where rabbit PBL were precultured at low cell density with antigen before being partitioned in limiting dilution cultures. This method provided a new tool for studies of various cellular aspects of the immune response. Moreover, it allowed the application of the limiting dilution analysis to PBL from unprimed animals. Later, the method was extended with success to human PBL, leading to studies of regulatory aspects of immunity in this species.

  18. Dst Profile Investigation of Long-Lasting Storms with Gamma Distribution and Diffusion-Like Distribution

    NASA Astrophysics Data System (ADS)

    Dong, Y.; Chou, J.; Damas, M. C.

    2016-12-01

    In this study, we focus on the Disturbance Storm Time (Dst) profile of long-lasting storms, which usually dips in a geomagnetic storm. Dst profiles are investigated with an inductive approach using the Gamma distribution function proportional to 1/(x^(k-1)) multiplied by exp(-theta*x). Energy dissipation is also modeled as a diffusion-like process where a 1-D diffusion profile would be equivalent to a Gamma distribution of k = 0.5. In an earlier study, profiles of fifteen storms were evaluated and analysis showed that a diffusion-like profile would serve as a better model compared to the Gamma distribution, suggesting the existence of a diffusion-like process in the energy dissipation in the Ring Current. Based on this result, the study was expanded to include 99 more Dst profiles (1998-2015). New methods are used to further the analysis in this study, including the addition of interplanetary structures (e.g., Corotating Interacting Region (CIRs), Sheath Field (SH), etc.) to categorize and explain patterns seen in Dst profiles. Our results so far show that sheath fields (SH) have the least deviation with each of their corresponding Gamma distribution functions as well as having a higher percentage of accurate fits.

  19. Can Long-lasting Insecticide-treated Bednets with Holes Protect Children from Malaria?

    PubMed

    Nonaka, Daisuke; Maazou, Abani; Yamagata, Shigeo; Oumarou, Issofou; Uchida, Takako; Jg Yacouba, Honoré; Toma, Nami; Takeuchi, Rie; Kobayashi, Jun; Mizoue, Tetsuya

    2014-09-01

    Although long-lasting insecticide-treated bednets (LLINs) have been widely used for malaria control, little is known about how the condition of LLINs affects the risk of malaria infection. The objective of this cross-sectional study was to examine the association between the use of LLINs with holes and caregiver-reported malaria diagnosed in children under five years of age (U5). Data were collected in Boboye health district, Niger, in 2010. Surveyors conducted interviews and bednet inspections in 1,034 households. If a household had a U5 child, the surveyor asked the caregiver whether the child had experienced a fever episode in the past two weeks that entailed standard treatment for uncomplicated malaria at a healthcare facility. The authors analyzed the association between the use of LLINs with holes and caregiver-reported malaria episodes in U5 children using logistic regression, adjusted for possible confounders. Of the 1,165 children included in the analysis, approximately half (53.3%) used an intact LLIN while far fewer (10.6%) used a LLIN with holes. Compared to children using an intact LLIN, children using a LLIN with holes were significantly more likely to have a caregiver-reported malaria episode (8.7% vs. 17.1%; odds ratio: 2.23; 95% confidence interval: 1.24-4.01). In this study site, LLINs with holes were less protective than intact LLINs.

  20. Can Long-lasting Insecticide-treated Bednets with Holes Protect Children from Malaria?

    PubMed Central

    Nonaka, Daisuke; Maazou, Abani; Yamagata, Shigeo; Oumarou, Issofou; Uchida, Takako; JG Yacouba, Honoré; Toma, Nami; Takeuchi, Rie; Kobayashi, Jun; Mizoue, Tetsuya

    2014-01-01

    Although long-lasting insecticide-treated bednets (LLINs) have been widely used for malaria control, little is known about how the condition of LLINs affects the risk of malaria infection. The objective of this cross-sectional study was to examine the association between the use of LLINs with holes and caregiver-reported malaria diagnosed in children under five years of age (U5). Data were collected in Boboye health district, Niger, in 2010. Surveyors conducted interviews and bednet inspections in 1,034 households. If a household had a U5 child, the surveyor asked the caregiver whether the child had experienced a fever episode in the past two weeks that entailed standard treatment for uncomplicated malaria at a healthcare facility. The authors analyzed the association between the use of LLINs with holes and caregiver-reported malaria episodes in U5 children using logistic regression, adjusted for possible confounders. Of the 1,165 children included in the analysis, approximately half (53.3%) used an intact LLIN while far fewer (10.6%) used a LLIN with holes. Compared to children using an intact LLIN, children using a LLIN with holes were significantly more likely to have a caregiver-reported malaria episode (8.7% vs. 17.1%; odds ratio: 2.23; 95% confidence interval: 1.24–4.01). In this study site, LLINs with holes were less protective than intact LLINs. PMID:25324687

  1. Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster.

    PubMed

    Trannoy, Séverine; Penn, Jill; Lucey, Kenia; Popovic, David; Kravitz, Edward A

    2016-04-26

    In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters.

  2. Doping and musculoskeletal system: short-term and long-lasting effects of doping agents.

    PubMed

    Nikolopoulos, Dimitrios D; Spiliopoulou, Chara; Theocharis, Stamatios E

    2011-10-01

    Doping is a problem that has plagued the world of competition and sports for ages. Even before the dawn of Olympic history in ancient Greece, competitors have looked for artificial means to improve athletic performance. Since ancient times, athletes have attempted to gain an unfair competitive advantage through the use of doping substances. A Prohibited List of doping substances and methods banned in sports is published yearly by the World Anti-Doping Agency. Among the substances included are steroidal and peptide hormones and their modulators, stimulants, glucocorticosteroids, β₂-agonists, diuretics and masking agents, narcotics, and cannabinoids. Blood doping, tampering, infusions, and gene doping are examples of prohibited methods indicated on the List. Apart from the unethical aspect of doping, as it abrogates fair-play's principle, it is extremely important to consider the hazards it presents to the health and well-being of athletes. The referred negative effects for the athlete's health have to do, on the one hand, by the high doses of the performance-enhancing agents and on the other hand, by the relentless, superhuman strict training that the elite or amateur athletes put their muscles, bones, and joints. The purpose of this article is to highlight the early and the long-lasting consequences of the doping abuse on bone and muscle metabolism. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

  3. Long-lasting regulation of hippocampal Bdnf gene transcription after contextual fear conditioning

    PubMed Central

    Mizuno, K.; Dempster, E.; Mill, J.; Giese, K.P.

    2014-01-01

    Long-term memory formation requires de novo protein synthesis and gene transcription. During contextual long-term memory formation brain-derived neurotrophic factor (BDNF) gene expression changes in conjunction with alterations of DNA methylation in the Bdnf gene. However, little is known about the molecular mechanisms underlying the maintenance and persistence of contextual long-term memory. Here, we examined the transcription of specific Bdnf exons in the hippocampus for long periods after contextual fear conditioning. We found changes in transcription lasting for at least 24 hours after contextual fear conditioning, with some sex-specific effects. In addition, hypomethylation at a CpG site in CpG island 2 located at the end of Bdnf exon III sequence was detected at 0.5 h and maintained for up to 24 h after contextual fear conditioning. The identification of these long-lasting changes in transcription and DNA methylation at the Bdnf gene suggests that BDNF might have a role for storage of contextual long-term memory in the hippocampus. PMID:22574690

  4. Parental imprisonment: long-lasting effects on boys' internalizing problems through the life course.

    PubMed

    Murray, Joseph; Farrington, David P

    2008-01-01

    Qualitative studies suggest that children react to parental imprisonment by developing internalizing as well as externalizing behaviors. However, no previous study has examined the effects of parental imprisonment on children's internalizing problems using standardized instruments, appropriate comparison groups, and long-term follow-up. Using prospective longitudinal data from the Cambridge Study in Delinquent Development, we compared boys separated because of parental imprisonment during their first 10 years of life with four control groups: boys who did not experience separation, boys separated because of hospitalization or death, boys separated for other reasons (usually parental disharmony), and boys whose parents were only imprisoned before the boys' births. Individual, parenting, and family risk factors for internalizing problems were measured when boys were ages 8-11 years. Separation because of parental imprisonment predicted boys' internalizing problems from age 14 to 48, even after controlling for childhood risk factors including parental criminality. Separation because of parental imprisonment also predicted the co-occurrence of internalizing and antisocial problems. These results suggest that parental imprisonment might cause long-lasting internalizing and antisocial problems for children.

  5. Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects

    PubMed Central

    Liu, Chen; Fu, Xuekun; Pan, Haobo; Wan, Peng; Wang, Lei; Tan, Lili; Wang, Kehong; Zhao, Ying; Yang, Ke; Chu, Paul K.

    2016-01-01

    A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications. PMID:27271057

  6. Regulatory T cells form stable and long-lasting cell cluster with myeloid dendritic cells (DC).

    PubMed

    Herman, Sonja; Krenbek, Dagmar; Klimas, Michael; Bonelli, Michael; Steiner, Carl W; Pietschmann, Peter; Smolen, Josef S; Scheinecker, Clemens

    2012-07-01

    Regulatory T cells (Treg) with the capacity to suppress T-cell proliferation exert various effects on T cell function. In addition, Treg have been shown to modulate the phenotype and function of antigen-presenting cells (APC) including dendritic cells (DC), B cells and monocytes/macrophages. However, the specific mechanism(s) of how Treg affect APC have not been entirely identified so far. In this study, we analyzed the interaction of human Treg and effector T cells (Teff) with peripheral blood myeloid and monocyte-derived dendritic cells in vitro. A strong tendency for cell cluster formation between Treg and DC was observed, which was dependent on the adhesion molecules ICAM-1, LFA-3 and ICAM-3. In addition, Treg were found to express higher levels of LFA-1, LFA-2, LFA-3 and ICAM-3 both before and after activation with anti-CD3 antibodies. Using in vitro live cell imaging, we were further able to show that Treg-DC cell clusters, in contrast to Teff-DC clusters, were stable and long lasting. Co-cultures of DC with Treg diminished the up-regulation of activation induced costimulatory molecule expression on DC, and further reduced the production of tumor necrosis factor alpha and stimulated the production of IL-4. In summary, our data indicate that Treg-DC cluster formation might enable Treg to modulate phenotypic and functional characteristics of DC and help to constrain Teff activation.

  7. Lynx reproduction--long-lasting life cycle of corpora lutea in a feline species.

    PubMed

    Jewgenow, Katarina; Painer, Johanna; Amelkina, Olga; Dehnhard, Martin; Goeritz, Frank

    2014-04-01

    A review of lynxes' reproductive biology and comparison between the reproductive cycles of the domestic cat and lynxes is presented. Three of the four lynx species (the bobcat excluded) express quite similar reproductive pattern (age at sexual maturity, estrus and pregnancy length, litter size). Similarly to the domestic cat, the bobcat is polyestric and can have more than one litter per year. Domestic cats and many other felid species are known to express anovulatory, pregnant and pseudo-pregnant reproductive cycles in dependence on ovulation induction and fertilization. The formation of corpora lutea (CLs) occurs after ovulation. In pregnant animals, luteal function ends with parturition, whereas during pseudo-pregnancy a shorter life span and lower hormone secretion are observed. The life cycle of corpora lutea in Eurasian lynxes is different from the pattern described in domestic cats. Lynx CLs produce progestagens in distinctive amounts permanently for at least two years, regardless of their origin (pregnancy or pseudo-pregnancy). It is suggested that long-lasting CLs induce a negative feedback to inactivate folliculogenesis, turning a normally polyestric cycle observed in most felids into a monoestric cycle in lynxes. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Long-lasting T cell responses to biological warfare vaccines in human vaccinees.

    PubMed

    Allen, Jennifer S; Skowera, Ania; Rubin, G James; Wessely, Simon; Peakman, Mark

    2006-07-01

    Medical countermeasures against biological warfare include the use of vaccines for anthrax and plague, which require repeated dosing and adjuvant to achieve adequate protection from threats such as inhalational anthrax and pneumonic plague. Despite the widespread use of these measures in preparation for recent military deployments, little is known about the cell-mediated immune response that is induced by these vaccines, in comparison with conventional vaccines, such as pertussis or tetanus-diphtheria vaccines. To examine this question, we used cytokine enzyme-linked immunospot assays to measure interferon-gamma, interleukin (IL)-2, IL-4, and IL-13-producing cells in military service personnel vaccinated during the Gulf War of 1990-1991. Our data indicate that 12-15 years after vaccination against anthrax and plague, antigen-specific T cell recall responses are present in the circulation and are comparable in magnitude to those for tetanus-diphtheria toxoids. Recall responses to anthrax were an approximately equal mixture of type 1 T helper cell (interferon-gamma and IL-2) and type 2 T helper cell (predominantly IL-13) responses, whereas plague cellular immunity was more polarized toward type 1 T helper cell responses. Responder cell frequency and type were similar to that against conventional tetanus-diphtheria (mixed type 1 and type 2 T helper cells) vaccine. When veterans were divided according to whether or not they reported multisymptom illness, there was no difference in the frequency or type of cellular response, although the number of cases in each group was small, and these data should be interpreted as preliminary. This study shows that, despite any putative limitations of vaccines for anthrax and plague in terms of achieving protective host immunity, long-lasting cell-mediated responses are generated with these agents.

  9. Fast Uptake and Long-Lasting Binding of Methamphetamine in the Human Brain

    PubMed Central

    Fowler, Joanna S.; Volkow, Nora D.; Logan, Jean; Alexoff, David; Telang, Frank; Wang, Gene-Jack; Wong, Christopher; Ma, Yeming; Kriplani, Aarti; Pradhan, Kith; Schlyer, David; Jayne, Millard; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog, Karen

    2008-01-01

    Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine’s uptake in brain was fast (peak uptake at 9 minutes) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 minutes) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine’s brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine’s fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans. PMID:18708148

  10. Anabolic steroids have long-lasting effects on male social behaviors.

    PubMed

    Salas-Ramirez, Kaliris Y; Montalto, Pamela R; Sisk, Cheryl L

    2010-04-02

    Anabolic androgenic steroids (AAS) use by adolescents is steadily increasing. Adolescence involves remodeling of steroid-sensitive neural circuits that mediate social behaviors, and previous studies using animal models document effects of AAS on male social behaviors. The present experiments tested whether AAS have persistent and more pronounced behavioral consequences when drug exposure occurs during adolescence as compared to exposure in adulthood. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or adulthood (63-77 days of age). As adults, subjects were tested two or four weeks after the last injection for either sexual behavior with a receptive female or male-male agonistic behavior in a resident-intruder test. Compared with vehicle-treated males, AAS-treated males, regardless of age of treatment, displayed fewer long intromissions and a significant increase in latency to the first long intromission, indicative of reduced potential to reach sexual satiety. Increased aggression was observed in males exposed to AAS compared with males treated with vehicle, independently of age of AAS treatment. However, unlike hamsters exposed to AAS in adulthood, hamsters exposed to AAS during adolescence did not display any submissive or risk-assessment behaviors up to 4 weeks after discontinuation of AAS treatment. Thus, AAS have long-lasting effects on male sexual and agonistic behaviors, with AAS exposure during adolescence resulting in a more pronounced reduction in submissive behavior compared to AAS exposure in adulthood. Published by Elsevier B.V.

  11. NONLINEAR FORCE-FREE MODELING OF A LONG-LASTING CORONAL SIGMOID

    SciTech Connect

    Savcheva, Antonia; Van Ballegooijen, Adriaan, E-mail: asavcheva@cfa.harvard.ed

    2009-10-01

    A study of the magnetic configuration and evolution of a long-lasting quiescent coronal sigmoid is presented. The sigmoid was observed by Hinode/XRT and Transition Region and Coronal Explorer (TRACE) between 2007 February 6 and 12 when it finally erupted. We construct nonlinear force-free field models for several observations during this period, using the flux-rope insertion method. The high spatial and temporal resolution of the X-Ray Telescope (XRT) allows us to finely select best-fit models that match the observations. The modeling shows that a highly sheared field, consisting of a weakly twisted flux rope embedded in a potential field, very wellmore » describes the structure of the X-ray sigmoid. The flux rope reaches a stable equilibrium, but its axial flux is close to the stability limit of about 5 x 10{sup 20} Mx. The relative magnetic helicity increases with time from February 8 until just prior to the eruption on February 12. We study the spatial distribution of the torsion parameter alpha in the vicinity of the flux rope, and find that it has a hollow-core distribution, i.e., electric currents are concentrated in a current layer at the boundary between the flux rope and its surroundings. The current layer is located near the bald patch separatrix surface (BPSS) of the magnetic configuration, and the X-ray emission appears to come from this current layer/BPSS, consistent with the Titov and Demoulin model. We find that the twist angle PHI of the magnetic field increases with time to about 2pi just prior to the eruption, but never reaches the value necessary for the kink instability.« less

  12. Long-lasting effect of NMDA receptor antagonist memantine on ethanol-cue association and relapse.

    PubMed

    Vengeliene, Valentina; Olevska, Anastasia; Spanagel, Rainer

    2015-12-01

    It is well known that the glutamatergic system plays a crucial role in alcohol addiction and especially in relapse-like behaviour. However, results of clinical studies on compounds that influence the activity of the glutamatergic system have been disappointing so far. The aim of our study was to establish treatment conditions under which the N-methyl-d-aspartate receptor (NMDAR) antagonist memantine may produce more reliable treatment effect with respect to alcohol relapse-like behaviour. For this purpose, male Wistar rats were trained to associate several discrete stimuli with ethanol delivery. Thereafter, half of the animals received a brief memory reactivation session followed by two administrations of 20 mg/kg of memantine, while the other half received the same treatment without memory reactivation. Afterwards, a cue-induced ethanol-seeking behaviour test was performed followed by repeated extinction sessions and a reacquisition test. Our data show that administration of memantine reduced responding on the ethanol-associated lever in a cue-induced ethanol-seeking test. This reduction did not depend on whether or not a memory reactivation session was introduced prior to memantine administration. Following extinction, however, reacquisition of ethanol self-administration was only impaired in the group where memantine was given after a short memory reactivation session, showing that this schedule of drug administration produced a long-lasting disruption of the association between the conditioned stimuli and the delivery of ethanol. In conclusion, we show that memantine disrupted the drug-cue association, which consequently interfered with relapse-like behaviour supporting the possibility that memantine is a treatment option for alcoholism. Our data supports the possibility that memantine is a treatment option for alcoholism. However, the effectiveness of this drug seems to lie in its ability to disrupt conditioned behaviours and should be given in conjunction

  13. ANABOLIC STEROIDS HAVE LONG-LASTING EFFECTS ON MALE SOCIAL BEHAVIORS

    PubMed Central

    Salas-Ramirez, Kaliris Y.; Montalto, Pamela R.; Sisk, Cheryl L.

    2010-01-01

    Anabolic androgenic steroids (AAS) use by adolescents is steadily increasing. Adolescence involves remodeling of steroid-sensitive neural circuits that mediate social behaviors, and previous studies using animal models document effects of AAS on male social behaviors. The present experiments tested whether AAS have persistent and more pronounced behavioral consequences when drug exposure occurs during adolescence as compared to exposure in adulthood. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or adulthood (63-77 days of age). As adults, subjects were tested two or four weeks after the last injection for either sexual behavior with a receptive female or male-male agonistic behavior in a resident-intruder test. Compared with vehicle-treated males, AAS-treated males, regardless of age of treatment, displayed fewer long intromissions and a significant increase in latency to the first long intromission, indicative of reduced potential to reach sexual satiety. Increased aggression was observed in males exposed to AAS compared with males treated with vehicle, independently of age of AAS treatment. However, unlike hamsters exposed to AAS in adulthood, hamsters exposed to AAS during adolescence did not display any submissive or risk-assessment behaviors up to 4 weeks after discontinuation of AAS treatment. Thus, AAS have long-lasting effects on male sexual and agonistic behaviors, with AAS exposure during adolescence resulting in a more pronounced reduction in submissive behavior compared to AAS exposure in adulthood. PMID:20036695

  14. Radiotherapy combined with the immunocytokine L19-IL2 provides long-lasting antitumor effects.

    PubMed

    Zegers, Catharina M L; Rekers, Nicolle H; Quaden, Dana H F; Lieuwes, Natasja G; Yaromina, Ala; Germeraad, Wilfred T V; Wieten, Lotte; Biessen, Erik A L; Boon, Louis; Neri, Dario; Troost, Esther G C; Dubois, Ludwig J; Lambin, Philippe

    2015-03-01

    Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which is dependent on ED-B expression. Mice were injected with syngeneic C51 colon carcinoma, Lewis lung carcinoma (LLC), or 4T1 mammary carcinoma cells. Tumor growth delay, underlying immunologic parameters, and treatment toxicity were evaluated after single-dose local tumor irradiation and systemic administration of L19-IL2 or equimolar controls. ED-B expression was high, intermediate, and low for C51, LLC, and 4T1, respectively. The combination therapy showed (i) a long-lasting synergistic effect for the C51 model with 75% of tumors being cured, (ii) an additive effect for the LLC model, and (iii) no effect for the 4T1 model. The combination treatment resulted in a significantly increased cytotoxic (CD8(+)) T-cell population for both C51 and LLC. Depletion of CD8(+) T cells abolished the benefit of the combination therapy. These data provide the first evidence for an increased therapeutic potential by combining radiotherapy with L19-IL2 in ED-B-positive tumors. This new opportunity in cancer treatment will be investigated in a phase I clinical study for patients with an oligometastatic solid tumor (NCT02086721). An animation summarizing our results is available at https://www.youtube.com/watch?v=xHbwQuCTkRc. ©2014 American Association for Cancer Research.

  15. Intrathecal pramoxine causes long-lasting spinal sensory and motor block in rats.

    PubMed

    Chou, An-Kuo; Chiu, Chong-Chi; Han, Ming-Ming; Chen, Yu-Wen; Wang, Jhi-Joung; Hung, Ching-Hsia

    2018-02-13

    The objective of this experiment was to investigate spinal anaesthetic effects of pramoxine and its comparison with bupivacaine, a long-lasting local anaesthetic. After intrathecal injection, three neurobehavioural assessments, which consisted of nociceptive, proprioceptive and motor block, were constructed in rats. The effects of bupivacaine and pramoxine (four doses of each drug) in a dose-related manner were conducted to obtain the ED 50 (50% effective dose). Pramoxine potency and duration at provoking spinal nociceptive, proprioceptive and motor block were compared with those of bupivacaine. We manifested that pramoxine provoked dose-relatedly spinal blockades of nociception, proprioception and motor function. Based on the ED 50 , the rank potency at producing spinal nociceptive, proprioceptive and motor block was bupivacaine (0.90 (0.82-1.02), 1.00 (0.92-1.08) and 1.16 (1.02-1.34) μmol/kg) greater (P < 0.01 for the differences) than pramoxine (15.47 (14.04-17.05), 16.46 (15.06-17.99), and 17.77 (16.48-19.15) μmol/kg). The spinal block duration created by bupivacaine was not predominantly different (P > 0.05 for the differences) from that created by pramoxine at the equipotent doses (ED 75 , ED 50 and ED 25 ). Our preclinical experiment indicated that pramoxine elicited a dose-related spinal block, was less potent than bupivacaine and had a similar duration of spinal block compared with bupivacaine. © 2018 Royal Pharmaceutical Society.

  16. Inter-tester reliability of selected clinical tests for long-lasting temporomandibular disorders.

    PubMed

    Julsvoll, Elisabeth Heggem; Vøllestad, Nina Køpke; Opseth, Gro; Robinson, Hilde Stendal

    2017-09-01

    Clinical tests used to examine patients with temporomandibular disorders vary in methodological quality, and some are not tested for reliability. The purpose of this cross-sectional study was to evaluate inter-tester reliability of clinical tests and a cluster of tests used to examine patients with long-lasting temporomandibular disorders. Forty patients with pain in the temporomandibular area treated by health-professionals were included. They were between 18-70 years, had 65 symptomatic (33 right/32 left) and 15 asymptomatic joints. Two manual therapists examined all participants with selected tests. Percentage agreement and the kappa coefficient ( k ) with 95% confidence interval (CI) were used to evaluate the tests with categorical outcomes. For tests with continuous outcomes, the relative inter-tester reliability was assessed by the intraclass-correlation-coefficient (ICC 3,1 , 95% CI) and the absolute reliability was calculated by the smallest detectable change (SDC). The best reliability among single tests was found for the dental stick test, the joint-sound test ( k  = 0.80-1.0) and range of mouth-opening (ICC 3,1 (95% CI) = 0.97 (0.95-0.98) and SDC = 4 mm). The reliability of cluster of tests was excellent with both four and five positive tests out of seven. The reliability was good to excellent for the clinical tests and the cluster of tests when performed by experienced therapists. The tests are feasible for use in the clinical setting. They require no advanced equipment and are easy to perform.

  17. Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.

    PubMed

    Fowler, Joanna S; Volkow, Nora D; Logan, Jean; Alexoff, David; Telang, Frank; Wang, Gene-Jack; Wong, Christopher; Ma, Yeming; Kriplani, Aarti; Pradhan, Kith; Schlyer, David; Jayne, Millard; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog, Karen

    2008-12-01

    Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.

  18. Long lasting egocentric disorientation induced by normal sensori-motor spatial interaction.

    PubMed

    Dupierrix, Eve; Gresty, Michael; Ohlmann, Théophile; Chokron, Sylvie

    2009-01-01

    Perception of the cardinal directions of the body, right-left, up-down, ahead-behind, which appears so absolute and fundamental to the organisation of behaviour can in fact, be modified. Perhaps unsurprisingly, it has been shown that prolonged distorted perception of the orientation of body axes can be a consequence of disordered sensori-motor signals, including long-term prismatic adaptation and lesions of the central nervous system. We report the novel and surprising finding that a long-lasting distortion of perception of personal space can also be induced by an ecological pointing task without the artifice of distorting normal sensori-motor relationships. Twelve right-handed healthy adults performed the task of pointing with their arms, without vision, to indicate their subjective 'straight ahead', a task often used to assess the Egocentric Reference. This was performed before, immediately, and one day after a second task intended to 'modulate' perception of spatial direction. The 'modulating' task lasted 5 minutes and consisted of asking participants to point with the right finger to targets that appeared only in one (right or left) half of a computer screen. Estimates of the 'straight-ahead' during pre-test were accurate (inferior to 0.3 degrees deviation). Significantly, up to one day after performing the modulating task, the subjective 'straight-ahead' was deviated (by approximately 3.2 degrees) to the same side to which subjects had pointed to targets. These results reveal that the perception of directional axes for behaviour is readily influenced by interactions with the environment that involve no artificial distortion of normal sensori-motor-spatial relationships and does not necessarily conform to the cardinal directions as defined by the anatomy of orthostatic posture. We thus suggest that perceived space is a dynamic construction directly dependent upon our past experience about the direction and/or the localisation of our sensori-motor spatial

  19. Durability associated efficacy of long-lasting insecticidal nets after five years of household use.

    PubMed

    Kweka, Eliningaya J; Himeidan, Yousif E; Mahande, Aneth M; Mwang'onde, Beda J; Msangi, Shandala; Mahande, Michael J; Mazigo, Humphrey D; Nyindo, Mramba

    2011-08-05

    Long-lasting insecticidal nets (LLINs) have been strongly advocated for use to prevent malaria in sub-Saharan Africa and have significantly reduced human-vector contact. PermaNet® 2.0 is among the five LLINs brands which have been given full approval by the WHO Pesticide Evaluation Scheme (WHOPES). The LLINs are expected to protect the malaria endemic communities, but a number of factors within the community can affect their durability and efficacy. This study evaluated the durability, efficacy and retention of PermaNet® 2.0 after five years of use in a Tanzanian community. Two to three day- old non blood-fed female mosquitoes from an insectary susceptible colony (An. gambiae s.s, this colony was established at TPRI from Kisumu, Kenya in 1992) and wild mosquito populations (An. arabiensis and Culex quinquefasciatus) were used in cone bioassay tests to assess the efficacy of mosquito nets. The knockdown effect was recorded after three minutes of exposure, and mortality was recorded after 24 hours post-exposure. Mortality of An. gambiae s.s from insectary colony was 100% while An. arabiensis and Cx.quinquefasciatus wild populations had reduced mortality. Insecticide content of the new (the bed net of the same brand but never used before) and used PermaNet® 2.0 was determined using High Performance Liquid Chromatography (HPLC). The results of this study suggest that, in order to achieve maximum protection against malaria, public health education focusing on bed net use and maintenance should be incorporated into the mass distribution of nets in communities.

  20. Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice.

    PubMed

    Rodríguez-Arias, Marta; Maldonado, Concepción; Vidal-Infer, Antonio; Guerri, Consuelo; Aguilar, María A; Miñarro, José

    2011-11-01

    Heavy binge drinking is increasingly frequent among adolescents, while ethanol (EtOH) is often used in combination with 3,4-methylenedioxymethamphetamine (MDMA). The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on motor activity, anxiety, and social behavior were evaluated in adult mice. The concentration of brain monoamines in the striatum, cortex, and hippocampus was measured following the behavioral test. Adolescent OF1 mice were exposed to ethanol (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PND 29 to 42). A total of eight injections of MDMA (10 or 20 mg/kg) were administered twice daily at 4-h intervals over two consecutive days, and this schedule was repeated 6 days later (PND 33, 34, 41, and 42). Behavioral tests and analysis of brain monoamines took place on PND 64 to 67. Exposure to MDMA during adolescence increased the anxiogenic response in the elevated plus maze, with adult mice spending less time in the open arms of the maze and exhibiting lower concentrations of DA in the striatum. A pattern of ethanol administration modeling binge drinking during adolescence enhanced these effects and undermined the hyperthermic response induced by MDMA. Passive avoidance was affected only when EtOH was administered alone. Juvenile administration of MDMA and alcohol was found to cause a decrease in monoamine levels in adulthood, as well as changes in social interaction behaviors, locomotor activity, increase measures of anxiety in the elevated plus maze (EPM), and decrease step-through latencies in passive avoidance test.

  1. Long lasting effects of the conversion from natural forest to poplar plantation on soil microbial communities.

    PubMed

    Vitali, Francesco; Mastromei, Giorgio; Senatore, Giuliana; Caroppo, Cesarea; Casalone, Enrico

    2016-01-01

    In this study, we evaluate the long-lasting effects on soil microbial communities of a change within a single land-use category, specifically the conversion from natural forest to forest plantation. To minimize the effects of impacts other than land-use (i.e., climatic and anthropogenic), we chose three sites within a Natural Park, with homogeneous orographic and soil texture characteristics. We compared microbial diversity in a total of 156 soil samples from two natural mixed forests and a similar forest converted to poplar plantation about thirty years ago. The diversity and structure of bacterial and fungal communities were investigated by terminal restriction fragments length polymorphism (T-RFLP) analysis of the 16S-rRNA gene and the ITS-rDNA regions, respectively. Bacterial and fungal communities from the forest plantation, compared to those from natural forest soils, showed different community structure and lower α-diversity values, consistently with the significantly higher pH values and lower organic matter content of those soils. β-diversity values, the number of measured and estimated dominant OTUs, and their distribution among the three sites showed that microbial communities from the two natural forests were much more similar to each other than they were to communities from the poplar plantation, suggesting an effect of the forest conversion on the composition and diversity of soil microbial communities. α-diversity in cultivated forest soils had narrower temporal fluctuations than in natural forest soils, suggesting higher temporal stability of microbial communities. Overall, we demonstrated that the conversion from natural forest to forest plantation altered soil microbial communities, changing their structure, lowering their diversity, and causing a spatial and temporal homogenization. Copyright © 2015 Elsevier GmbH. All rights reserved.

  2. Decreasing proportion of Anopheles darlingi biting outdoors between long-lasting insecticidal net distributions in peri-Iquitos, Amazonian Peru.

    PubMed

    Prussing, Catharine; Moreno, Marta; Saavedra, Marlon P; Bickersmith, Sara A; Gamboa, Dionicia; Alava, Freddy; Schlichting, Carl D; Emerson, Kevin J; Vinetz, Joseph M; Conn, Jan E

    2018-02-20

    In Loreto Department, Peru, a successful 2005-2010 malaria control programme (known as PAMAFRO) included massive distribution of long-lasting insecticidal nets (LLINs). Additional local distribution of LLINs occurred in individual villages, but not between 2012 and 2015. A 2011-2012 study of the primary regional malaria vector Anopheles darlingi detected a trend of increased exophagy compared with pre-PAMAFRO behaviour. For the present study, An. darlingi were collected in three villages in Loreto in 2013-2015 to test two hypotheses: (1) that between LLIN distributions, An. darlingi reverted to pre-intervention biting behaviour; and, (2) that there are separate sub-populations of An. darlingi in Loreto with distinct biting behaviour. In 2013-2015 An. darlingi were collected by human landing catch during the rainy and dry seasons in the villages of Lupuna and Cahuide. The abundance of An. darlingi varied substantially across years, villages and time periods, and there was a twofold decrease in the ratio of exophagic:endophagic An. darlingi over the study period. Unexpectedly, there was evidence of a rainy season population decline in An. darlingi. Plasmodium-infected An. darlingi were detected indoors and outdoors throughout the night, and the monthly An. darlingi human biting rate was correlated with the number of malaria cases. Using nextRAD genotyping-by-sequencing, 162 exophagic and endophagic An. darlingi collected at different times during the night were genotyped at 1021 loci. Based on model-based and non-model-based analyses, all genotyped An. darlingi belonged to a homogeneous population, with no evidence for genetic differentiation by biting location or time. This study identified a decreasing proportion of exophagic An. darlingi in two villages in the years between LLIN distributions. As there was no evidence for genetic differentiation between endophagic and exophagic An. darlingi, this shift in biting behaviour may be the result of behavioural

  3. Insulin degludec overdose may lead to long-lasting hypoglycaemia through its markedly prolonged half-life.

    PubMed

    Uchida, J; Oikawa, Y; Katsuki, T; Takeda, H; Shimada, A; Kawai, T

    2018-02-01

    Overdose of insulin often causes long-lasting severe hypoglycaemia. Insulin degludec has the longest duration of action among the available insulin products; thus, an overdose of insulin degludec can lead to long-lasting hypoglycaemia. In the present paper, we report the case of a woman with long-lasting hypoglycaemia attributable to insulin degludec overdose and markedly prolonged insulin degludec half-life. A 64-year-old woman with Type 2 diabetes receiving insulin therapy was taken to an emergency department because of disturbed consciousness 21 h after self-injection of 300 units of insulin degludec (4.34 units/kg). Her plasma glucose level was 2.3 mmol/l. She received repeated intravenous boluses of dextrose for 43 h with continuous intravenous dextrose infusion, but no improvement in long-lasting hypoglycaemia or consciousness was observed. Considering the possibility of adrenal insufficiency, intravenous dexamethasone was administered, and her plasma glucose levels subsequently remained above 5.5 mmol/l without intravenous dextrose boluses. She gradually regained consciousness. A total of 34 h after the overdose, her plasma immunoreactive insulin levels were markedly increased and then gradually declined over ~400 h. The insulin degludec half-life was 40.76 h. Although the reported half-life of insulin degludec in the body is ~25 h when administered in standard doses (0.4-0.8 units/kg), no study has investigated its half-life after overdose. In the present case, the half-life of insulin degludec was ~1.6 times longer than that observed with standard doses, probably leading to long-lasting hypoglycaemia. Physicians should be aware of the possibility of unexpected long-lasting severe hypoglycaemia resulting from insulin degludec overdose. © 2017 Diabetes UK.

  4. Role of manganese in red long-lasting phosphorescence of manganese-doped diopside for in vivo imaging

    SciTech Connect

    Lecointre, A.; Bessière, A.; Priolkar, K.R.; Gourier, D.; Wallez, G.; Viana, B.

    2013-05-15

    Highlights: ► Long-lasting phosphorescence of CaMgSi{sub 2}O{sub 6}:Mn is studied for bioimaging application. ► CaMgSi{sub 2}O{sub 6}:Mn yields orange and red luminescence of Mn{sup II}{sub Ca} and Mn{sup II}{sub Mg}, respectively. ► Red Mn{sup II}{sub Mg} emission dominates long-lasting phosphorescence spectra. ► Mn mainly substitutes Mg. ► Mn{sup II}{sub Mg} plays the role of hole trap in the persistent luminescence mechanism. - Abstract: Materials with red long-lasting phosphorescence, such as Mn{sup II}-doped diopsides, can be used for small animal in vivo imaging. CaMgSi{sub 2}O{sub 6}:Mn powders with various amounts of Mn were prepared by sol–gel to investigate their long-lasting phosphorescence mechanism. X-ray diffraction, X-ray absorption fine and near-edge structure and electron paramagnetic resonance showed that manganese is quantitatively introduced in the structure as Mn{sup II}. Most of the Mn doping ions substitute Mg and possess a highly elongated octahedral environment. While photoluminescence and X-ray excited optical luminescence spectra show both orange (585 nm) and red (685 nm) {sup 4}T{sub 1} ({sup 4}G) → {sup 6}A{sub 1} ({sup 6}S) emission of Mn{sup II}{sub Ca} and Mn{sup II}{sub Mg}, respectively, Mn{sup II}{sub Mg} red emission dominates long-lasting phosphorescence and thermally stimulated luminescence spectra. These results point to Mn{sup II}{sub Mg} as the preferential hole trap and recombination center in the long-lasting phosphorescence mechanism. An intense persistent red emission suitable for in vivo imaging probes is obtained for the highest nominal Mn content (7.5%)

  5. Long-lasting attentional influence of negative and taboo words in an auditory variant of the emotional Stroop task.

    PubMed

    Bertels, Julie; Kolinsky, Régine; Pietrons, Elise; Morais, José

    2011-02-01

    Using an auditory adaptation of the emotional and taboo Stroop tasks, the authors compared the effects of negative and taboo spoken words in mixed and blocked designs. Both types of words elicited carryover effects with mixed presentations and interference with blocked presentations, suggesting similar long-lasting attentional effects. Both were also relatively resilient to the long-lasting influence of the preceding emotional word. Hence, contrary to what has been assumed (Schmidt & Saari, 2007), negative and taboo words do not seem to differ in terms of the temporal dynamics of the interdimensional shifting, at least in the auditory modality. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  6. System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania.

    PubMed

    Beer, Netta; Ali, Abdullah S; de Savigny, Don; Al-Mafazy, Abdul-Wahiyd H; Ramsan, Mahdi; Abass, Ali K; Omari, Rahila S; Björkman, Anders; Källander, Karin

    2010-06-18

    Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain high effective coverage, there is need

  7. System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania

    PubMed Central

    2010-01-01

    Background Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. Methods Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. Results The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). Conclusions Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain

  8. Planning long lasting insecticide treated net campaigns: should households’ existing nets be taken into account?

    PubMed Central

    2013-01-01

    Background Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. Methods A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net ‘decay’ parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered

  9. Planning long lasting insecticide treated net campaigns: should households' existing nets be taken into account?

    PubMed

    Yukich, Joshua; Bennett, Adam; Keating, Joseph; Yukich, Rudy K; Lynch, Matt; Eisele, Thomas P; Kolaczinski, Kate

    2013-06-14

    Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net 'decay' parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered. Where pre-campaign coverage

  10. Double Neutron Star Mergers and Short Gamma-ray Bursts: Long-lasting High-energy Signatures and Remnant Dichotomy

    NASA Astrophysics Data System (ADS)

    Murase, Kohta; Toomey, Michael W.; Fang, Ke; Oikonomou, Foteini; Kimura, Shigeo S.; Hotokezaka, Kenta; Kashiyama, Kazumi; Ioka, Kunihito; Mészáros, Peter

    2018-02-01

    The recent detection of gravitational waves and electromagnetic counterparts from the double neutron star merger event GW+EM170817 supports the standard paradigm of short gamma-ray bursts (SGRBs) and kilonovae/macronovae. It is important to reveal the nature of the compact remnant left after the merger, either a black hole or neutron star, and their physical link to the origin of the long-lasting emission observed in SGRBs. The diversity of the merger remnants may also lead to different kinds of transients that can be detected in future. Here we study the high-energy emission from the long-lasting central engine left after the coalescence, under certain assumptions. In particular, we consider the X-ray emission from a remnant disk and the nonthermal nebular emission from disk-driven outflows or pulsar winds. We demonstrate that late-time X-ray and high-frequency radio emission can provide useful constraints on properties of the hidden compact remnants and their connections to long-lasting SGRB emission, and we discuss the detectability of nearby merger events through late-time observations at ∼30–100 days after the coalescence. We also investigate the GeV–TeV gamma-ray emission that occurs in the presence of long-lasting central engines and show the importance of external inverse Compton radiation due to upscattering of X-ray photons by relativistic electrons in the jet. We also search for high-energy gamma rays from GW170817 in the Fermi-LAT data and report upper limits on such long-lasting emission. Finally, we consider the implications of GW+EM170817 and discuss the constraints placed by X-ray and high-frequency radio observations.

  11. Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus

    PubMed Central

    Clarkson, Cheryl; Antunes, Flora M.

    2016-01-01

    Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. SIGNIFICANCE STATEMENT Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of

  12. Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus.

    PubMed

    Clarkson, Cheryl; Antunes, Flora M; Rubio, Maria E

    2016-09-28

    Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at

  13. Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats.

    PubMed

    Burgos, H; Cofré, C; Hernández, A; Sáez-Briones, P; Agurto, R; Castillo, A; Morales, B; Zeise, M L

    2015-09-15

    Methylphenidate (MPH) is widely used as a "nootropic" agent and in the treatment of disorders of attention, and has been shown to modulate synaptic plasticity in vitro. Here we present in vivo evidence that this MPH-induced metaplasticity can last long after the end of treatment. MPH (0, 0.2, 1 and 5mg/kg) was administered daily to male rats from postnatal day 42 for 15 days. The animals were tested daily in a radial maze. Long-term potentiation (LTP), a marker of neural plasticity, was induced in vivo in the prefrontal cortex after 2-3h, 15-18 days or 5 months without treatment. The behavioral performance of the 1mg/kg group improved, while that of animals that had received 5mg/kg deteriorated. In the 1 and 5mg/kg groups LTP induced 2-3h after the last MPH treatment was twice as large as in the controls. Further, 15-18 days after the last MPH administration, in groups receiving 1 and 5mg/kg, LTP was about fourfold higher than in controls. However, 5 months later, LTP in the 1mg/kg group was similar to controls and in the 5mg/kg group LTP could not be induced at all. No significant changes of LTP were seen in the low-dose group of animals (0.2mg/kg). Thus, firstly, doses of MPH that improve learning coincide approximately with those that augment LTP. Secondly, MPH-induced increases in LTP can last for several weeks, but these may disappear over longer periods or deteriorate at high doses. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Early activation of microglia triggers long-lasting impairment of adult neurogenesis in the olfactory bulb.

    PubMed

    Lazarini, Françoise; Gabellec, Marie-Madeleine; Torquet, Nicolas; Lledo, Pierre-Marie

    2012-03-14

    Microglia, the innate immune cells of the brain, engulf and eliminate cellular debris during brain injury and disease. Recent observations have extended their roles to the healthy brain, but the functional impact of activated microglia on neural plasticity has so far been elusive. To explore this issue, we investigated the role of microglia in the function of the adult olfactory bulb network in which both sensory afferents and local microcircuits are continuously molded by the arrival of adult-born neurons. We show here that the adult olfactory bulb hosts a large population of resident microglial cells. Deafferentation of the olfactory bulb resulted in a transient activation of microglia and a concomitant reduction of adult olfactory bulb neurogenesis. One day after sensory deafferentation, microglial cells proliferate in the olfactory bulb, and their numbers peaked at day 3, and reversed at day 7 after lesion. Similar lesions performed on immunodeficient mice demonstrate that the both innate and adaptive lymphocyte responses are dispensable for the lesion-induced microglial proliferation and activation. In contrast, when mice were treated with an antiinflammatory drug to prevent microglial activation, olfactory deafferentation did not reduce adult neurogenesis, showing that activated microglial cells per se, and not the lack of sensory experience, relates to the survival of adult-born neurons. We conclude that the status of the resident microglia in the olfactory bulb is an important factor directly regulating the survival of immature adult-born neurons.

  15. Long lasting paleolandscapes stability of the French Massif Central during the Mesozoic

    NASA Astrophysics Data System (ADS)

    Ricordel-Prognon, C.; Thiry, M.; Theveniaut, H.; Lagroix, F.

    2009-04-01

    , and more importantly no Jurassic cover was preserved (if such a cover was even deposited?) on the massif. Consequently, the Massif Central probably never did support an important (more than 500 m) sedimentary cover during the Mesozoic. These paleosurface ages provide important constraints to crustal dynamics modeling. Identification and dating of the successive continental unconformities are evidence for long lasting continental evolution and landscape stability of large areas of the Massif Central during the Mesozoic. The alternative hypothesis was that the Massif Central was subsidizing during Mesozoic time and covered with a 2,000 m thick sedimentary series, which was fairly quickly eroded during early Tertiary (Barbarand et al., 2001). In the future, making substantial progress in paleoweathering profiles dating, especially in the scope of improving time resolution, will allow attempting efficient correlation between the continental records and the diverse processes involved in their development (eustatism, climate, global and regional tectonics). Moreover, progress in dating paleoweathering features and continental azoic deposits, will allow to develop a "continental stratigraphy" of climatic and geomorphological events and to establish a mass balances between weathering/erosion weathering/erosion on land and deposition in basins. References Barbarand J., Lucazeau F., Pagel M., Séranne M., 2001, Burial and exhumation history of the south-eastern Massif Central (France) constrained by apatite fission track thermochronology. Tectonophysics, 335, 3-4, p. 275-290. Besse, J., Courtillot, V., 2003. Apparent true polar wander and the geometry of the geomagnetic field over the last 200 Myr: Correction: Journal of Geophysical Research, 108, p. 2300. Cogné, J.P., 2003. PaleoMac: a MacintoshTM application for treating paleomagnetic data and making plate reconstructions. Geochemistry Geophysics Geosystems, 4 (1), 1007. Edel J.B., Duringer P., 1997, The apparent polar

  16. Metabolism of 5'alpha,8'-cycloabscisic acid, a highly potent and long-lasting abscisic acid analogue, in radish seedlings.

    PubMed

    Todoroki, Yasushi; Sawada, Masao; Matsumoto, Miyuki; Tsukada, Shigeko; Ueno, Kotomi; Isaka, Masatoshi; Owaki, Mariko; Hirai, Nobuhiro

    2004-01-15

    We synthesized 5'alpha,8'-cycloabscisic acid (CycloABA), a highly potent and long-lasting abscisic acid (ABA) analogue, by a different method from that reported before. CycloABA fed to radish seedlings had more metabolic tolerance than ABA. The major metabolite of CycloABA was the glucose conjugate, which was the minor metabolite of ABA. The 8'-hydroxylated metabolite and its cyclized isomer, which were major metabolites of ABA, were not found as metabolites of CycloABA. The present results suggest that the highly potent and long-lasting activity of CycloABA is caused by resistance to ABA 8'-hydroxylase, and that CycloABA is partially metabolized to the glucose conjugate by ABA glucosyltransferase.

  17. ZnGa2O4:Cr3+: a new red long-lasting phosphor with high brightness.

    PubMed

    Bessière, Aurélie; Jacquart, Sylvaine; Priolkar, Kaustubh; Lecointre, Aurélie; Viana, Bruno; Gourier, Didier

    2011-05-23

    ZnGa2O4:Cr3+ is shown to be a new bright red UV excited long-lasting phosphor potentially suitable for in vivo imaging due to its 650 nm-750 nm emission range. Photoluminescence and X-ray excited radioluminescence show the 2E → 4A2 emission lines of both ideal Cr3+ and Cr3+ distorted by a neighboring antisite defect while long-lasting phosphorescence (LLP) and thermally stimulated luminescence (TSL) almost exclusively occur via distorted Cr3+. The most intense LLP is obtained with a nominal Zn deficiency and is related to a TSL peak at 335K. A mechanism for LLP and TSL is proposed, whereby the antisite defect responsible for the distortion at Cr3+ acts as a deep trap.

  18. Long-lasting luminescence in ZnGa2O4: Cr3+ through persistent energy transfer

    NASA Astrophysics Data System (ADS)

    Li, Lei; Wang, Yinhai; Huang, Haiju; Li, Hong; Zhao, Hui

    2016-01-01

    Cr3+-doped zinc gallate (ZnGa2O4) near-infrared (NIR) phosphors were synthesized via a high temperature solid state method. The luminescence properties of the phosphors were studied systematically. A significant spectra overlap between the emission of ZnGa2O4 and the absorption of Cr3+ was observed and 300 nm excitation exhibited the most excellent long-lasting luminescence properties among the three main excitation bands. Luminescence intensity was changed with the ratio of Ga3+/Cr3+ and the blue host emission of ZnGa2O4 was suppressed when doping Cr3+ into ZnGa2O4. The fluorescence decay curves of blue emission of ZnGa2O4 with different Cr3+ doping concentrations indicated that the lifetime of ZnGa2O4 at 505 nm become shorter with the increase of the Cr3+ concentration. Herein, a possible mechanism of long-lasting luminescence in ZnGa2O4: Cr3+ was proposed that the NIR long-lasting luminescence in ZnGa2O4: Cr3+ comes from the persistent energy transfer from ZnGa2O4 to Cr3+.

  19. Disease activity in patients with long-lasting rheumatoid arthritis is associated with changes in peripheral blood lymphocyte subpopulations.

    PubMed

    Smoleńska, Żaneta; Pawłowska, Justyna; Daca, Agnieszka; Soroczyńska-Cybula, Monika; Witkowski, Jacek; Bryl, Ewa M

    2012-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease and it is known that lymphocytes play a major role in its pathogenesis. However, there have been no comprehensive studies on the changes in peripheral blood lymphocyte (PBL) subpopulations expressing different clusters of differentiation (CD) in patients with long-lasting RA. The aim of our study was to measure the main subpopulations of PBL, expression of costimulatory marker CD28, and activation status of CD4+ T cells depending on clinical disease activity in long-lasting RA. The study comprised 60 patients with RA and 19 healthy volunteers. Disease activity, the proportion and number of the main PBL subpopulations (T, B, natural killer [NK], and NK T cells [NKT]), the expression of costimulatory marker CD28, and the activation status of CD4+ T cells were evaluated on the same day. A multicolor flow cytometry with marked monoclonal antibodies was used for the assessment of lymphocyte subpopulations. The percentage of CD3+CD4+, NKT, CD4+CD28-, CD8+CD28-, CD4+CD69+, CD4+CD25+, and CD4+HLA-DR+ was significantly higher in RA compared with the control group. A higher proportion of CD4+CD28- was associated with more active disease, while an inverse correlation was observed for B cells. The proportion of CD4+CD28- was not associated with disease activity. The number of CD4+CD69+ cells in RA patients increased with increasing DAS28, while the number of CD4+HLA-DR+ T cells showed no such association. Our results have shown for the first time an association between the phenotype patterns of PBL T, B, and NKT and RA activity in patients with long-lasting disease, which reinforces the hypothesis that PBL play an important role in modifying or maintaining the disease activity.

  20. Cost-Effectiveness of Long-Lasting Insecticide-Treated Hammocks in Preventing Malaria in South-Central Vietnam

    PubMed Central

    Morel, Chantal M.; Thang, Ngo Duc; Erhart, Annette; Xa, Nguyen Xuan; Peeters Grietens, Koen; Xuan Hung, Le; Thuan, Le Khan; Van Ky, Pham; Hung, Nguyen Manh; Coosemans, Marc; D'Alessandro, Umberto; Mills, Anne

    2013-01-01

    Background Despite much success in reducing the burden of malaria in Vietnam, pockets of malaria persist and eliminating them remains an important development goal. In central Vietnam, insecticide-treated hammocks have recently been introduced to help counter the disease in the highly forested, mountainous areas, where other measures have so far been unsuccessful. This study assesses the cost-effectiveness of using long-lasting insecticide-treated hammocks in this area. Methods and Findings This cost-effectiveness study was run alongside a randomized control trial testing the efficacy of the long-lasting insecticide-treated hammocks. Data were collected through an exit survey, a household survey, expenditure records and key informant interviews. The study estimates that under normal (non-trial) conditions the total net societal cost per malaria episode averted in using long-lasting insecticide-treated hammocks in this area was 126 USD. Cost per hammock, including insecticidal netting, sewing, transport, and distribution was found to be approximately 11.76 USD per hammock. Average savings per episode averted were estimated to be $14.60 USD for the health system and 14.37 USD for households (including both direct and indirect cost savings). The study estimates that the annual financial outlay required of government to implement this type of programme to be 3.40 USD per person covered per year. Conclusion The study finds that the use of a hammock intervention could represent good value for money to help prevent malaria in more remote areas, where traditional control measures such as insecticide-treated bednets and indoor residual spraying are insufficient or inappropriate to control malaria. However, the life span of the hammock–the number of years over which it effectively deters mosquitoes–has a significant impact on the cost-effectiveness of the intervention and study results should be interpreted in light of the evidence on effectiveness gathered in the years

  1. Tennessee and Florida: Continuity and Change in Long-Lasting State Performance Funding Systems for Higher Education. CCRC Brief. Number 43

    ERIC Educational Resources Information Center

    Dougherty, Kevin J.; Natow, Rebecca S.

    2010-01-01

    This study analyzes changes over time in long-lasting state performance funding systems for higher education. It addresses two research questions: First, in what ways have long-lasting systems changed over time in funding levels, indicators used to allocate funds, and measures used for those indicators? Second, what political actors, actions, and…

  2. Palatable Hyper-Caloric Foods Impact on Neuronal Plasticity.

    PubMed

    Morin, Jean-Pascal; Rodríguez-Durán, Luis F; Guzmán-Ramos, Kioko; Perez-Cruz, Claudia; Ferreira, Guillaume; Diaz-Cintra, Sofia; Pacheco-López, Gustavo

    2017-01-01

    Neural plasticity is an intrinsic and essential characteristic of the nervous system that allows animals "self-tuning" to adapt to their environment over their lifetime. Activity-dependent synaptic plasticity in the central nervous system is a form of neural plasticity that underlies learning and memory formation, as well as long-lasting, environmentally-induced maladaptive behaviors, such as drug addiction and overeating of palatable hyper-caloric (PHc) food. In western societies, the abundance of PHc foods has caused a dramatic increase in the incidence of overweight/obesity and related disorders. To this regard, it has been suggested that increased adiposity may be caused at least in part by behavioral changes in the affected individuals that are induced by the chronic consumption of PHc foods; some authors have even drawn attention to the similarity that exists between over-indulgent eating and drug addiction. Long-term misuse of certain dietary components has also been linked to chronic neuroimmune maladaptation that may predispose individuals to neurodegenerative conditions such as Alzheimer's disease. In this review article, we discuss recent evidence that shows how consumption of PHc food can cause maladaptive neural plasticity that converts short-term ingestive drives into compulsive behaviors. We also discuss the neural mechanisms of how chronic consumption of PHc foods may alter brain function and lead to cognitive impairments, focusing on prenatal, childhood and adolescence as vulnerable neurodevelopmental stages to dietary environmental insults. Finally, we outline a societal agenda for harnessing permissive obesogenic environments.

  3. Low-frequency stimulation cancels the high-frequency-induced long-lasting effects in the rat medial vestibular nuclei.

    PubMed

    Grassi, S; Pettorossi, V E; Zampolini, M

    1996-05-15

    In rat brainstem slices, we investigated the effects of low-frequency stimulation (LFS) of the primary vestibular afferents on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN). LFS induced long-term effects, the sign of which depended on whether the vestibular neurons were previously conditioned by HFS. In unconditioned slices, LFS evoked modifications of the responses that were similar to those observed after HFS but had a smaller extension. In fact, LFS caused long-lasting potentiation of the N1 wave in the MVN ventral portion (Vp) and long-lasting depression of the N2 wave in the MVN dorsal portion (Dp), whereas it provoked small and variable effects on the N1 wave. By contrast, when the synaptic transmission was already conditioned, LFS influenced the synaptic responses oppositely, reducing or annulling the HFS long-term effects. This phenomenon was specifically induced by LFS, because HFS was not able to cause it. The involvement of NMDA receptors in mediating the LFS long-term effects was supported by the fact that AP-5 prevented their induction. In addition, the annulment of HFS long-term effects by LFS was also demonstrated by the shift in the latency of the evoked unitary potentials after LFS. In conclusion, we suggest that the reduction of the previously induced conditioning could represent a cancellation mechanism, useful to quickly adapt the vestibular system to continuous different needs and to avoid saturation.

  4. Serotonin 5-HT2 receptor activation induces a long-lasting amplification of spinal reflex actions in the rat

    PubMed Central

    Machacek, D W; Garraway, S M; Shay, B L; Hochman, S

    2001-01-01

    C-fibre activation induces a long-term potentiation (LTP) in the spinal flexion reflex in mammals, presumably to provide enhanced reflexive protection of damaged tissue from further injury. Descending monoaminergic pathways are thought to depress sensory input but may also amplify spinal reflexes; the mechanisms of this modulation within the spinal cord remain to be elucidated. We used electrical stimulation of primary afferents and recordings of motor output, in the rat lumbar spinal cord maintained in vitro, to demonstrate that serotonin is capable of inducing a long-lasting increase in reflex strength at all ages examined (postnatal days 2–12). Pharmacological analyses indicated an essential requirement for activation of 5-HT2C receptors while 5-HT1A/1B, 5-HT7 and 5-HT2A receptor activation was not required. In addition, primary afferent-evoked synaptic potentials recorded in a subpopulation of laminae III-VI spinal neurons were similarly facilitated by 5-HT. Thus, serotonin receptor-evoked facilitatory actions are complex, and may involve alterations in neuronal properties at both motoneuronal and pre-motoneuronal levels. This study provides the first demonstration of a descending transmitter producing a long-lasting amplification in reflex strength, accomplished by activating a specific serotonin receptor subtype. It is suggested that brain modulatory systems regulate reflex pathways to function within an appropriate range of sensori-motor gain, facilitating reflexes in behavioural situations requiring increased sensory responsiveness. PMID:11711573

  5. A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.

    PubMed

    Silva, Carlos D; Neves, Ana F; Dias, Ana I; Freitas, Hugo J; Mendes, Sheena M; Pita, Inês; Viana, Sofia D; de Oliveira, Paulo A; Cunha, Rodrigo A; Fontes Ribeiro, Carlos A; Prediger, Rui D; Pereira, Frederico C

    2014-04-01

    Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis.

  6. Long-lasting and sex-specific consequences of elevated egg yolk testosterone for social behavior in Japanese quail.

    PubMed

    Schweitzer, Cécile; Goldstein, Michael H; Place, Ned J; Adkins-Regan, Elizabeth

    2013-01-01

    In birds, early exposure to steroid hormones deposited in egg yolks is hypothesized to result in long-lasting effects on brain and behavior. However, the long-term effects of maternal androgens on the development of social behavior, and whether these could interfere with the effects of the endogenous gonadal hormones that mediate sexual differentiation, remain poorly known. To answer these questions, we enhanced yolk testosterone by injecting testosterone (T) in oil into Japanese quail (Coturnix japonica) eggs prior to incubation. Vehicle-injected (V) eggs served as controls. From age 3 weeks to 8 weeks, sexual development was measured using morphological and physiological traits, and social behavior was measured, including male-typical sexual behavior. In females, treatment with testosterone boosted growth. Males from T-injected eggs developed an affiliative preference for familiar females and differed from V-injected males in the acoustic features of their crows, whereas sexual interest (looking behavior) and copulatory behavior were not affected. These long-lasting and sex-specific yolk testosterone effects on the development of dimorphic traits, but without disrupting sexual differentiation of reproductive behavior suggest potential organizational effects of maternal testosterone, but acting through separate processes than the endocrine mechanisms previously shown to control sexual differentiation. Separate processes could reflect the action of androgens at different times or on multiple targets that are differentially sensitive to steroids or develop at different rates. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

    SciTech Connect

    Alba, Martha P.; Suarez, Carlos F.; Varela, Yahson; Patarroyo, Manuel A.; Bermudez, Adriana; Patarroyo, Manuel E.

    2016-09-02

    Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPII{sub L} 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche{sup −} rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche{sup +} orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory. - Highlights: • Stereo-electronic and topochemical rules associated with FPLLI immunological memory. • Presence of very high long-lasting antibody titres against Plasmodium falciparum Spz. • Protective memory induction associated with a binding capacity to HLA-DRβ1*. • gauche{sup −} rotamer orientation in p8 polar residue is related to is related to immunological memory.

  8. Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract

    PubMed Central

    Dai, Jin; Zhang, Tianyuan; Wang, Luying; Shao, Lili; Zhu, Cuiming; Zhang, Yuyang; Failor, Courtney; Schenken, Robert; Baseman, Joel; He, Cheng

    2016-01-01

    Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarum can spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarum strain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivo imaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of the C. muridarum organisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridarum inoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract. PMID:27271744

  9. Intrinsic cellular and molecular properties of in vivo hippocampal synaptic plasticity are altered in the absence of key synaptic matrix molecules.

    PubMed

    Jansen, Stephan; Gottschling, Christine; Faissner, Andreas; Manahan-Vaughan, Denise

    2017-08-01

    Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca 2+ -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO). We observed that the profiles of synaptic potentiation and depression in the dentate gyrus (DG) were profoundly altered compared to plasticity profiles in wild-type littermates (WT). Specifically, synaptic depression was amplified in a frequency-dependent manner and although late-LTP (>24 hr) was expressed following strong afferent tetanization, the early component of LTP (<75 min post-tetanization) was absent. LTP (>4 hr) elicited by weaker tetanization was equivalent in WT and KO animals. Furthermore, this latter form of LTP was NMDAR-dependent in WT but not KO mice. Scrutiny of DG receptor expression revealed significantly lower levels of both the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor, of the metabotropic glutamate receptor, mGlu5 and of the L-type calcium channel, Ca v 1.3 in KO compared to WT animals. Homer 1a and of the P/Q-type calcium channel, Ca v 1.2 were unchanged in KO mice. Taken together, findings suggest that in mice that lack multiple ECM proteins, synaptic plasticity is intact, but is fundamentally different. © 2017 Wiley Periodicals, Inc.

  10. At Long Last

    ERIC Educational Resources Information Center

    Cooper, Kenneth J.

    2012-01-01

    Since 1980, Tufts has offered a minor called Africa in the New World, but for reasons lost to time, the private university north of Boston did not join other schools in the 1960s and 1970s in creating a major in what was usually called Black studies. A faculty-student committee's recommendation in 1972 to do so went unimplemented. African-American…

  11. Synaptic plasticity by antidromic firing during hippocampal network oscillations.

    PubMed

    Bukalo, Olena; Campanac, Emilie; Hoffman, Dax A; Fields, R Douglas

    2013-03-26

    Learning and other cognitive tasks require integrating new experiences into context. In contrast to sensory-evoked synaptic plasticity, comparatively little is known of how synaptic plasticity may be regulated by intrinsic activity in the brain, much of which can involve nonclassical modes of neuronal firing and integration. Coherent high-frequency oscillations of electrical activity in CA1 hippocampal neurons [sharp-wave ripple complexes (SPW-Rs)] functionally couple neurons into transient ensembles. These oscillations occur during slow-wave sleep or at rest. Neurons that participate in SPW-Rs are distinguished from adjacent nonparticipating neurons by firing action potentials that are initiated ectopically in the distal region of axons and propagate antidromically to the cell body. This activity is facilitated by GABA(A)-mediated depolarization of axons and electrotonic coupling. The possible effects of antidromic firing on synaptic strength are unknown. We find that facilitation of spontaneous SPW-Rs in hippocampal slices by increasing gap-junction coupling or by GABA(A)-mediated axon depolarization resulted in a reduction of synaptic strength, and electrical stimulation of axons evoked a widespread, long-lasting synaptic depression. Unlike other forms of synaptic plasticity, this synaptic depression is not dependent upon synaptic input or glutamate receptor activation, but rather requires L-type calcium channel activation and functional gap junctions. Synaptic stimulation delivered after antidromic firing, which was otherwise too weak to induce synaptic potentiation, triggered a long-lasting increase in synaptic strength. Rescaling synaptic weights in subsets of neurons firing antidromically during SPW-Rs might contribute to memory consolidation by sharpening specificity of subsequent synaptic input and promoting incorporation of novel information.

  12. Functional magnetic resonance connectivity studies in infants born preterm: suggestions of proximate and long-lasting changes in language organization.

    PubMed

    Kwon, Soo Hyun; Scheinost, Dustin; Vohr, Betty; Lacadie, Cheryl; Schneider, Karen; Dai, Feng; Sze, Gordon; Constable, R Todd; Ment, Laura R

    2016-03-01

    Sophisticated neuroimaging strategies demonstrate alterations in functional connectivity at school age, adolescence, and young adulthood in individuals born preterm. Recent data suggest these alterations are present in the postnatal period prior to term-equivalent age in neonates born preterm. Likewise, functional organization increases across development, but the influence of preterm birth on this fundamental infrastructure is immediate and unchanging. This article briefly reviews the current methods of measuring functional connectivity throughout development in those born preterm, and the association of functional connectivity with language disorders. Taken together, these data suggest that the effects of preterm birth on the functional organization of language in the developing brain are both proximate and long-lasting. © 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.

  13. Long Lasting Impairment of Taste and Smell as Side Effect of Lithium Carbonate in a Cluster Headache Patient.

    PubMed

    de Coo, Ilse F; Haan, Joost

    2016-07-01

    Preventive treatment with lithium carbonate is a therapeutic option for chronic cluster headache. Lithium can lead to a broad spectrum of severe side effects, many of which are generally unknown. One week after starting treatment with lithium, a 55-year-old man with chronic cluster headache noticed a strange and unpleasant taste of various foods and a diminished smell. After 4 weeks, he decided to stop the therapy because of these complaints, but 9 months later both taste and smell still had not returned to normal. We present the first description of long-lasting dysgeusia and hyposmia as a side effect of lithium therapy in cluster headache. Dysgeusia has only rarely been reported as a side effect of lithium in other conditions and hyposmia has not previously been reported. Physicians should be aware of this rare, but severe, side effect when prescribing lithium. © 2016 American Headache Society.

  14. Long-lasting deficits in hedonic and nucleus accumbens reactivity to sweet rewards by sugar overconsumption during adolescence.

    PubMed

    Naneix, Fabien; Darlot, Florence; Coutureau, Etienne; Cador, Martine

    2016-03-01

    Adolescence is a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system might constitute an important factor in vulnerability to pathological development. In spite of the dramatic increase in the consumption of sweet palatable foods during adolescence in our modern societies, the long-term consequences of such exposure on brain reward processing remain poorly understood. Here, we investigated in rats the long-lasting effects of sugar overconsumption during their adolescence on their adult reactivity to the hedonic properties of sweet rewards. Adolescent rats with continuous access to 5% sucrose solution (from postnatal day 30-46) showed escalating intake. At adulthood (post-natal day 70), using two-bottle free choice tests, sucrose-exposed rats showed lower intake than non-exposed rats suggesting decreased sensitivity to the rewarding properties of sucrose. In Experiment 1, we tested their hedonic-related orofacial reactions to intraoral infusion of tasty solutions. We showed that sucrose-exposed rats presented less hedonic reactions in response to sweet tastes leaving the reactivity to water or quinine unaltered. Hence, in Experiment 2, we observed that this hedonic deficit is associated with lower c-Fos expression levels in the nucleus accumbens, a brain region known to play a central role in hedonic processing. These findings demonstrate that a history of high sucrose intake during the critical period of adolescence induces long-lasting deficits in hedonic treatment that may contribute to reward-related disorders. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Bimodal Long-lasting Components in Short Gamma-Ray Bursts: Promising Electromagnetic Counterparts to Neutron Star Binary Mergers

    NASA Astrophysics Data System (ADS)

    Kisaka, Shota; Ioka, Kunihito; Sakamoto, Takanori

    2017-09-01

    Long-lasting emission of short gamma-ray bursts (GRBs) is crucial to reveal the physical origin of the central engine as well as to detect electromagnetic (EM) counterparts to gravitational waves (GWs) from neutron star binary mergers. We investigate 65 X-ray light curves of short GRBs, which is six times more than previous studies, by combining both Swift/BAT and XRT data. The light curves are found to consist of two distinct components at >5σ with bimodal distributions of luminosity and duration, I.e., extended (with a timescale of ≲103 s) and plateau emission (with a timescale of ≳103 s), which are likely the central engine activities, but not afterglows. The extended emission has an isotropic energy comparable to the prompt emission, while the plateau emission has ˜0.01-1 times this energy. Half (50%) of our sample has both components, while the other half is consistent with having both components. This leads us to conjecture that almost all short GRBs have both the extended and plateau emission. The long-lasting emission can be explained by the jets from black holes with fallback ejecta, and could power macronovae (or kilonovae) like GRB 130603B and GRB 160821B. Based on the observed properties, we quantify the detectability of EM counterparts to GWs, including the plateau emission scattered to the off-axis angle, with CALET/HXM, INTEGRAL/SPI-ACS, Fermi/GBM, MAXI/GSC, Swift/BAT, XRT, the future ISS-Lobster/WFI, Einstein Probe/WXT, and eROSITA.

  16. Perinatal Caffeine, Acting on Maternal Adenosine A1 Receptors, Causes Long-Lasting Behavioral Changes in Mouse Offspring

    PubMed Central

    Fredholm, Bertil B.

    2008-01-01

    Background There are lingering concerns about caffeine consumption during pregnancy or the early postnatal period, partly because there may be long-lasting behavioral changes after caffeine exposure early in life. Methodology/Principal Findings We show that pregnant wild type (WT) mice given modest doses of caffeine (0.3 g/l in drinking water) gave birth to offspring that as adults exhibited increased locomotor activity in an open field. The offspring also responded to cocaine challenge with greater locomotor activity than mice not perinatally exposed to caffeine. We performed the same behavioral experiments on mice heterozygous for adenosine A1 receptor gene (A1RHz). In these mice signaling via adenosine A1 receptors is reduced to about the same degree as after modest consumption of caffeine. A1RHz mice had a behavioral profile similar to WT mice perinatally exposed to caffeine. Furthermore, it appeared that the mother's genotype, not offspring's, was critical for behavioral changes in adult offspring. Thus, if the mother partially lacked A1 receptors the offspring displayed more hyperactivity and responded more strongly to cocaine stimulation as adults than did mice of a WT mother, regardless of their genotype. This indicates that long-term behavioral alterations in the offspring result from the maternal effect of caffeine, and not a direct effect on fetus. WT offspring from WT mother but having a A1R Hz grandmother preserved higher locomotor response to cocaine. Conclusions/Significance We suggest that perinatal caffeine, by acting on adenosine A1 receptors in the mother, causes long-lasting behavioral changes in the offspring that even manifest themselves in the second generation. PMID:19092996

  17. Pilot study assessing the effectiveness of long-lasting permethrin-impregnated clothing for the prevention of tick bites.

    PubMed

    Vaughn, Meagan F; Meshnick, Steven R

    2011-07-01

    Tick-borne diseases such as Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis are a significant concern for many thousands of workers who have frequent and unavoidable exposure to tick-infested habitats. Many North Carolina state employees with outdoor occupations report multiple tick bites each year, indicating that existing tick preventive strategies may be underutilized or ineffective. Treatment of clothing with permethrin, a nontoxic chemical with insecticidal, knockdown, and repellent properties, is highly effective against ticks. However, most permethrin products must be reapplied after several washings to maintain insecticidal activity. Recently, a factory-based method for long-lasting permethrin impregnation of clothing has been developed by Insect Shield, Inc., that allows clothing to retain insecticidal activity for over 70 washes. A nonrandomized open label pilot study was conducted to determine the effectiveness of Insect Shield-treated clothing for the prevention of tick bites among 16 outdoor workers from the North Carolina Division of Water Quality under actual field conditions. Participants completed questionnaires at the start of follow-up (March, 2008) and at the end of follow-up (September, 2008), and tick bites and outdoor work hours were reported on weekly tick bite logs for the entire follow-up period. Subjects wearing Insect Shield-treated clothing had a 93% reduction (p < 0.0001) in the total incidence of tick bites compared to subjects using standard tick bite prevention measures. This study provides preliminary evidence that long-lasting permethrin-impregnated clothing may be highly effective against tick bites.

  18. Long-lasting adverse effects after short-term low-dose treatment with metoclopramide for vomiting.

    PubMed

    Dahl, Eilif; Diskin, Arthur L

    2014-01-01

    Metoclopramide is commonly used to treat vomiting caused by seasickness and acute gastroenteritis on cruise ships and serious adverse effects have not been reported from use at sea. We report severe long-lasting adverse effects in a young female seafarer following short-term, low-dose use of metoclopramide. During rough seas a 25-year-old female musician on a cruise vessel presented with nausea and vomiting. She was given intramuscular metoclopramide 10 mg and diphenhydramine 25 mg. Vomiting stopped after the injections, but she felt tired, confused and dizzy. She then had been taking metoclopramide 5-10 mg a day, but stopped after a total per oral dose of 30 mg as she developed disturbing symptoms that she related to the medication, including dizziness, anxiety, fatigue, depression and involuntary movements (twitches, jerks, ticks, and tremors of the eyelids, tongue, neck, fingers, arms and legs). Neurological examination, blood tests, electrocardiography and magnetic resonance imaging of the brain were all normal. Although gradually reduced in strength and frequency, the adverse effects were very disturbing for about 10 months, but at 13 months she was almost fully recovered. For many years numerous vomiting sea travellers have been successfully treated with a single parenteral 10 mg dose of metoclopramide. There are no obvious reasons why our previously healthy patient experienced such serious and long-lasting side effects after low-dose, short-term metoclopramide administration. Until more is known, metoclopramide should be reserved for debilitating cases - and only be given after other remedies have been tried and found ineffective.

  19. IFN-α induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells.

    PubMed

    Coomans de Brachène, Alexandra; Dos Santos, Reinaldo S; Marroqui, Laura; Colli, Maikel L; Marselli, Lorella; Mirmira, Raghavendra G; Marchetti, Piero; Eizirik, Decio L

    2018-03-01

    IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes. We tested whether expression of these mediators of beta cell loss is reversible upon IFN-α withdrawal or IFN-α pathway inhibition. IFN-α-induced MHC class I overexpression, ER stress and inflammation were evaluated by flow cytometry, immunofluorescence and real-time PCR in human EndoC-βH1 cells or human islets exposed to IFN-α with or without the presence of Janus kinase (JAK) inhibitors. Protein expression was evaluated by western blot. IFN-α-induced expression of inflammatory and ER stress markers returned to baseline after 24-48 h following cytokine removal. In contrast, MHC class I overexpression at the cell surface persisted for at least 7 days. Treatment with JAK inhibitors, when added with IFN-α, prevented MHC class I overexpression, but when added 24 h after IFN-α exposure these inhibitors failed to accelerate MHC class I return to baseline. IFN-α mediates a long-lasting and preferential MHC class I overexpression in human beta cells, which is not affected by the subsequent addition of JAK inhibitors. These observations suggest that IFN-α-stimulated long-lasting MHC class I expression may amplify beta cell antigen presentation during the early phase of type 1 diabetes and that IFN-α inhibitors might need to be used at very early stages of the disease to be effective.

  20. The Novelty-Seeking Phenotype Modulates the Long-Lasting Effects of Intermittent Ethanol Administration during Adolescence

    PubMed Central

    Montagud-Romero, Sandra; Daza-Losada, Manuel; Vidal-Infer, Antonio; Maldonado, Concepción; Aguilar, María A.; Miñarro, Jose; Rodríguez-Arias, Marta

    2014-01-01

    The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels - measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype. PMID:24658541

  1. TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

    SciTech Connect

    Alba, Martha P.; Suarez, Carlos F.; Universidad del Rosario, Bogotá D. C.

    2016-09-02

    Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPII{sub L} 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche{sup −} rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. Thismore » data, in association with previously-described p3 and p7 apolar residues having gauche{sup +} orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory. - Highlights: • Stereo-electronic and topochemical rules associated with FPLLI immunological memory. • Presence of very high long-lasting antibody titres against Plasmodium falciparum Spz. • Protective memory induction associated with a binding capacity to HLA-DRβ1*. • gauche{sup −} rotamer orientation in p8 polar residue is related to is related to immunological memory.« less

  2. Reductions in frontocortical cytokine levels are associated with long-lasting alterations in reward valuation after methamphetamine.

    PubMed

    Stolyarova, Alexandra; Thompson, Andrew B; Barrientos, Ruth M; Izquierdo, Alicia

    2015-03-13

    Alterations in reward valuation are thought to have a central role at all stages of the addiction process. We previously reported work aversion in an effortful T-maze task following a binge exposure to methamphetamine, and no such changes in effort following escalating doses. Limitations of the T-maze task include its two available options, with an effort requirement, in the form of increasing barrier height, varying incrementally as a function of time, and reward magnitudes held constant. Reward preferences and choices, however, are likely affected by the number of options available and the manner in which alternatives are presented. In the present experiment, we investigated the long-lasting, off-drug effects of methamphetamine on reward choices in a novel effortful maze task with three possible courses of action, each associated with different effort requirements and reward magnitudes. Neuroinflammatory responses associated with drug exposure, proposed as one of the mechanisms contributing to suboptimal choices on effort-based tasks, were also examined. We investigated region-specific changes in pro- and anti-inflammatory markers in the mesocorticolimbic pathway after methamphetamine, and their relationship with animals' reward choices. We observed long-lasting, increased sensitivity to differences in reward magnitude in the methamphetamine group: animals were more likely to overcome greater effort costs to obtain larger rewards on our novel effortful maze task. These behavioral changes were strongly predicted by pronounced decreases in frontocortical cytokines, but not amygdalar or striatal markers. The present results provide the first evidence that neuroinflammatory processes are associated with alterations in reward valuation during protracted drug withdrawal.

  3. Long-lasting pathological consequences of overexpression-induced α-synuclein spreading in the rat brain.

    PubMed

    Rusconi, Raffaella; Ulusoy, Ayse; Aboutalebi, Helia; Di Monte, Donato A

    2018-01-30

    Increased expression of α-synuclein can initiate its long-distance brain transfer, representing a potential mechanism for pathology spreading in age-related synucleinopathies, such as Parkinson's disease. In this study, the effects of overexpression-induced α-synuclein transfer were assessed over a 1-year period after injection of viral vectors carrying human α-synuclein DNA into the rat vagus nerve. This treatment causes targeted overexpression within neurons in the dorsal medulla oblongata and subsequent diffusion of the exogenous protein toward more rostral brain regions. Protein advancement and accumulation in pontine, midbrain, and forebrain areas were contingent upon continuous overexpression, because death of transduced medullary neurons resulted in cessation of spreading. Lack of sustained spreading did not prevent the development of long-lasting pathological changes. Particularly remarkable were findings in the locus coeruleus, a pontine nucleus with direct connections to the dorsal medulla oblongata and greatly affected by overexpression-induced transfer in this model. Data revealed progressive degeneration of catecholaminergic neurons that proceeded long beyond the time of spreading cessation. Neuronal pathology in the locus coeruleus was accompanied by pronounced microglial activation and, at later times, astrocytosis. Interestingly, microglial activation was also featured in another region reached by α-synuclein transfer, the central amygdala, even in the absence of frank neurodegeneration. Thus, overexpression-induced spreading, even if temporary, causes long-lasting pathological consequences in brain regions distant from the site of overexpression but anatomically connected to it. Neurodegeneration may be a consequence of severe protein burden, whereas even a milder α-synuclein accumulation in tissues affected by protein transfer could induce sustained microglial activation. © 2018 The Authors. Aging Cell published by the Anatomical Society and

  4. The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging.

    PubMed

    Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria

    2016-09-15

    Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

    PubMed

    Montagud-Romero, Sandra; Daza-Losada, Manuel; Vidal-Infer, Antonio; Maldonado, Concepción; Aguilar, María A; Miñarro, Jose; Rodríguez-Arias, Marta

    2014-01-01

    The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype.

  6. Long-lasting effects of land use history on soil fungal communities in second-growth tropical rain forests.

    PubMed

    Bachelot, Benedicte; Uriarte, María; Zimmerman, Jess K; Thompson, Jill; Leff, Jonathan W; Asiaii, Ava; Koshner, Jenny; McGuire, Krista

    2016-09-01

    Our understanding of the long-lasting effects of human land use on soil fungal communities in tropical forests is limited. Yet, over 70% of all remaining tropical forests are growing in former agricultural or logged areas. We investigated the relationship among land use history, biotic and abiotic factors, and soil fungal community composition and diversity in a second-growth tropical forest in Puerto Rico. We coupled high-throughput DNA sequencing with tree community and environmental data to determine whether land use history had an effect on soil fungal community descriptors. We also investigated the biotic and abiotic factors that underlie such differences and asked whether the relative importance of biotic (tree diversity, basal tree area, and litterfall biomass) and abiotic (soil type, pH, iron, and total carbon, water flow, and canopy openness) factors in structuring soil fungal communities differed according to land use history. We demonstrated long-lasting effects of land use history on soil fungal communities. At our research site, most of the explained variation in soil fungal composition (R 2  = 18.6%), richness (R 2  = 11.4%), and evenness (R 2  = 10%) was associated with edaphic factors. Areas previously subject to both logging and farming had a soil fungal community with lower beta diversity and greater evenness of fungal operational taxonomic units (OTUs) than areas subject to light logging. Yet, fungal richness was similar between the two areas of historical land use. Together, these results suggest that fungal communities in disturbed areas are more homogeneous and diverse than in areas subject to light logging. Edaphic factors were the most strongly correlated with soil fungal composition, especially in areas subject to light logging, where soils are more heterogenous. High functional tree diversity in areas subject to both logging and farming led to stronger correlations between biotic factors and fungal composition than in areas subject

  7. Long-Lasting Cortical Reorganization as the Result of Motor Imagery of Throwing a Ball in a Virtual Tennis Court

    PubMed Central

    Cebolla, Ana M.; Petieau, Mathieu; Cevallos, Carlos; Leroy, Axelle; Dan, Bernard; Cheron, Guy

    2015-01-01

    In order to characterize the neural signature of a motor imagery (MI) task, the present study investigates for the first time the oscillation characteristics including both of the time-frequency measurements, event related spectral perturbation and intertrial coherence (ITC) underlying the variations in the temporal measurements (event related potentials, ERP) directly related to a MI task. We hypothesize that significant variations in both of the time-frequency measurements underlie the specific changes in the ERP directly related to MI. For the MI task, we chose a simple everyday task (throwing a tennis ball), that does not require any particular motor expertise, set within the controlled virtual reality scenario of a tennis court. When compared to the rest condition a consistent, long-lasting negative fronto-central ERP wave was accompanied by significant changes in both time frequency measurements suggesting long-lasting cortical activity reorganization. The ERP wave was characterized by two peaks at about 300 ms (N300) and 1000 ms (N1000). The N300 component was centrally localized on the scalp and was accompanied by significant phase consistency in the delta brain rhythms in the contralateral central scalp areas. The N1000 component spread wider centrally and was accompanied by a significant power decrease (or event related desynchronization) in low beta brain rhythms localized in fronto-precentral and parieto-occipital scalp areas and also by a significant power increase (or event related synchronization) in theta brain rhythms spreading fronto-centrally. During the transition from N300 to N1000, a contralateral alpha (mu) as well as post-central and parieto-theta rhythms occurred. The visual representation of movement formed in the minds of participants might underlie a top-down process from the fronto-central areas which is reflected by the amplitude changes observed in the fronto-central ERPs and by the significant phase synchrony in contralateral fronto

  8. In diabetic Charcot neuroarthropathy impaired microvascular function is related to long lasting metabolic control and low grade inflammatory process.

    PubMed

    Araszkiewicz, Aleksandra; Soska, Jacek; Borucka, Katarzyna; Olszewska, Marta; Niedzwiecki, Pawel; Wierusz-Wysocka, Bogna; Zozulinska-Ziolkiewicz, Dorota

    2015-09-01

    The aim of this study was to assess microvascular function associated with the occurrence of Charcot neuroarthropathy (CN) in patients with diabetes. We evaluated 70 diabetic patients (54 men) with Charcot neuroarthropathy (CN-DM), median age 59 (IQR: 51-62), mean disease duration 16±8years. The control group were 70 subjects with diabetes and without Charcot neuroarthropathy (DM), 54 men, median age 60 (54-62), mean diabetes duration 15±7years. We assessed metabolic control of diabetes, serum C-reactive protein concentration (CRP) and cardiovascular autonomic neuropathy (CAN). We used AGE-Reader to measure skin autofluorescence (AF) associated with accumulation of advanced glycation end products that reflects long lasting metabolic control. Microvascular function was examined by laser Doppler flowmetry (PERIFLUX 5000) with thermal hyperemia (TH) and postocclusive reactive hyperemia (PORH). CN-DM patients as compared to DM subjects had lower HbA1c level [7.6 (6.6-8.4) vs 8.4 (7.3-9.7)%, p<0.001], lower eGFR [75.9±24.1 vs 86.6±17.8ml/min/1.73m(2), p=0.003], higher CRP serum concentration [3.8 (2.3-10.1) vs 1.9 (0.8-4.4)mg/l, p<0.001] and higher skin autofluorescence [2.8 (2.5-3.1) vs 2.6 (2.3-2.9)AU, p=0.03]. The cardiovascular autonomic neuropathy (CAN) was more frequently diagnosed in CN-DM subjects [59 vs 27%, p<0.001]. The peak flow during thermal hyperemia (THmax) was lower in CN-DM subjects as compared to DM group [156 (93-240) vs 235 (155-300)PU, p=0.001]. We found negative correlation between THmax and CRP concentration (Rs=-0.34, p=0.003), TG concentration (Rs=-0.37, p=0.002) and skin AF (Rs=-0.32, p=0.04) and positive correlation between THmax and HDL cholesterol level (Rs=0.42, p<0.001) in CN-DM patients. There was also a positive correlation between PORHpeak and HDL cholesterol level (Rs=-0.23, p=0.04). Deterioration of microvascular function and autonomic system dysfunction are present in Charcot neuroarthropathy. Impaired microvascular reactivity

  9. Cost and cost effectiveness of long-lasting insecticide-treated bed nets - a model-based analysis

    PubMed Central

    2012-01-01

    Background The World Health Organization recommends that national malaria programmes universally distribute long-lasting insecticide-treated bed nets (LLINs). LLINs provide effective insecticide protection for at least three years while conventional nets must be retreated every 6-12 months. LLINs may also promise longer physical durability (lifespan), but at a higher unit price. No prospective data currently available is sufficient to calculate the comparative cost effectiveness of different net types. We thus constructed a model to explore the cost effectiveness of LLINs, asking how a longer lifespan affects the relative cost effectiveness of nets, and if, when and why LLINs might be preferred to conventional insecticide-treated nets. An innovation of our model is that we also considered the replenishment need i.e. loss of nets over time. Methods We modelled the choice of net over a 10-year period to facilitate the comparison of nets with different lifespan (and/or price) and replenishment need over time. Our base case represents a large-scale programme which achieves high coverage and usage throughout the population by distributing either LLINs or conventional nets through existing health services, and retreats a large proportion of conventional nets regularly at low cost. We identified the determinants of bed net programme cost effectiveness and parameter values for usage rate, delivery and retreatment cost from the literature. One-way sensitivity analysis was conducted to explicitly compare the differential effect of changing parameters such as price, lifespan, usage and replenishment need. Results If conventional and long-lasting bed nets have the same physical lifespan (3 years), LLINs are more cost effective unless they are priced at more than USD 1.5 above the price of conventional nets. Because a longer lifespan brings delivery cost savings, each one year increase in lifespan can be accompanied by a USD 1 or more increase in price without the cheaper net

  10. Developmental exposure to the SSRI citalopram causes long-lasting behavioural effects in the three-spined stickleback (Gasterosteus aculeatus).

    PubMed

    Kellner, M; Porseryd, T; Porsch-Hällström, I; Borg, B; Roufidou, C; Olsén, K H

    2018-01-01

    Selective Serotonin re-uptake inhibitors (SSRIs) are a class of psychotropic drugs used to treat depression in both adolescents and pregnant or breast-feeding mothers as well as in the general population. Recent research on rodents points to long-lasting behavioural effects of pre- and perinatal exposure to SSRIs which last into adulthood. In fish however, studies on effects of developmental exposure to SSRIs appears to be non-existent. In order to study effects of developmental SSRI exposure in fish, three-spine sticklebacks were exposed to 1.5 µg/l of the SSRI citalopram in the ambient water for 30 days, starting two days post-fertilisation. After approximately 100 days of remediation in clean water the fish were put through an extensive battery of behavioural tests. Feeding behaviour was tested as the number of bites against a piece of food and found to be increased in the exposed fish. Aggression levels were measured as the number of bites against a mirror image during 10 min and was also found to be significantly increased in the exposed fish. Novel tank behaviour and locomotor activity was tested in an aquarium that had a horizontal line drawn half-way between the bottom and the surface. Neither the latency to the first transition to the upper half, nor the number of transitions or the total time spent in the upper half was affected by treatment. Locomotor activity was significantly reduced in the exposed fish. The light/dark preference was tested in an aquarium where the bottom and walls were black on one side and white on the other. The number of transitions to the white side was significantly reduced in the exposed fish but there was no effect on the latency to the first transition or the total time spent in the white half. The results in the current study indicate that developmental SSRI exposure causes long-lasting behavioural effects in fish and contribute to the existing knowledge about SSRIs as environmental pollutants.

  11. Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens.

    PubMed

    Scherrer, Alexandra U; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Furrer, Hansjakob; Calmy, Alexandra; Cavassini, Matthias; Elzi, Luigia; Vernazza, Pietro L; Bernasconi, Enos; Ledergerber, Bruno; Günthard, Huldrych F

    2012-01-01

    The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments. We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3-6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression. Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3-6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3-6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1-42.8), p<0.001). The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.

  12. Performance of honey bee colonies under a long-lasting dietary exposure to sublethal concentrations of the neonicotinoid insecticide thiacloprid.

    PubMed

    Siede, Reinhold; Faust, Lena; Meixner, Marina D; Maus, Christian; Grünewald, Bernd; Büchler, Ralph

    2017-07-01

    Substantial honey bee colony losses have occurred periodically in the last decades. The drivers for these losses are not fully understood. The influence of pests and pathogens are beyond dispute, but in addition, chronic exposure to sublethal concentrations of pesticides has been suggested to affect the performance of honey bee colonies. This study aims to elucidate the potential effects of a chronic exposure to sublethal concentrations (one realistic worst-case concentration) of the neonicotinoid thiacloprid to honey bee colonies in a three year replicated colony feeding study. Thiacloprid did not significantly affect the colony strength. No differences between treatment and control were observed for the mortality of bees, the infestation with the parasitic mite Varroa destructor and the infection levels of viruses. No colony losses occurred during the overwintering seasons. Furthermore, thiacloprid did not influence the constitutive expression of the immunity-related hymenoptaecin gene. However, upregulation of hymenoptaecin expression as a response to bacterial challenge was less pronounced in exposed bees than in control bees. Under field conditions, bee colonies are not adversely affected by a long-lasting exposure to sublethal concentrations of thiacloprid. No indications were found that field-realistic and higher doses exerted a biologically significant effect on colony performance. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  13. Oral combined therapy with probiotics and alloantigen induces B cell-dependent long-lasting specific tolerance.

    PubMed

    Mercadante, Ana C T; Perobelli, Suelen M; Alves, Ana P G; Gonçalves-Silva, Triciana; Mello, Wallace; Gomes-Santos, Ana C; Miyoshi, Anderson; Azevedo, Vasco; Faria, Ana M C; Bonomo, Adriana

    2014-02-15

    Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the treatment of hematologic malignancies. Although aHSCT provides a good response against the malignant cells (graft-versus-leukemia [GVL]), it also leads to the development of graft-versus-host disease (GVHD), a severe disease with high mortality and morbidity rates. Therapy for GVHD is commonly based on nonspecific immunosupression of the transplanted recipient, resulting in the concomitant inhibition of the GVL effect. In this study, we propose an alternative approach to specifically suppress GVHD while sparing the GVL, based on oral treatment of transplant donors with recipient Ags, associated with the intake of probiotic Lactococcus lactis as tolerogenic adjuvant (combined therapy). We show that treatment of C57BL/6 donor mice with combined therapy before the transplant protects the recipients F1 (C57BL/6 × BAL/c) mice from clinical and pathological manifestations of disease, resulting in 100% survival rate. Importantly, the animals keep the immunological competence maintaining the GVL response as well as the response to third-party Ags. The protection is specific, long lasting and dependent on donor IL-10-sufficient B cells activity, which induces regulatory T cells in the host. These data suggest that combined therapy is a promising strategy for prevention of GVHD with preservation of GVL, opening new possibilities to treat human patients subjected to transplantation.

  14. Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

    PubMed

    Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

    2016-08-01

    With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

  15. TBP-like Protein (TLP) Disrupts the p53-MDM2 Interaction and Induces Long-lasting p53 Activation.

    PubMed

    Maeda, Ryo; Tamashiro, Hiroyuki; Takano, Kazunori; Takahashi, Hiro; Suzuki, Hidefumi; Saito, Shinta; Kojima, Waka; Adachi, Noritaka; Ura, Kiyoe; Endo, Takeshi; Tamura, Taka-Aki

    2017-02-24

    Stress-induced activation of p53 is an essential cellular response to prevent aberrant cell proliferation and cancer development. The ubiquitin ligase MDM2 promotes p53 degradation and limits the duration of p53 activation. It remains unclear, however, how p53 persistently escapes MDM2-mediated negative control for making appropriate cell fate decisions. Here we report that TBP-like protein (TLP), a member of the TBP family, is a new regulatory factor for the p53-MDM2 interplay and thus for p53 activation. We found that TLP acts to stabilize p53 protein to ensure long-lasting p53 activation, leading to potentiation of p53-induced apoptosis and senescence after genotoxic stress. Mechanistically, TLP interferes with MDM2 binding and ubiquitination of p53. Moreover, single cell imaging analysis shows that TLP depletion accelerates MDM2-mediated nuclear export of p53. We further show that a cervical cancer-derived TLP mutant has less p53 binding ability and lacks a proliferation-repressive function. Our findings uncover a role of TLP as a competitive MDM2 blocker, proposing a novel mechanism by which p53 escapes the p53-MDM2 negative feedback loop to modulate cell fate decisions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Long-lasting alterations of the immune system by ionizing radiation exposure: implications for disease development among atomic bomb survivors.

    PubMed

    Kusunoki, Yoichiro; Hayashi, Tomonori

    2008-01-01

    The immune systems of the atomic-bomb (A-bomb) survivors were damaged proportionately to irradiation levels at the time of the bombing over 60 years ago. Although the survivor's immune system repaired and regenerated as the hematopoietic system has recovered, significant residual injury persists, as manifested by abnormalities in lymphoid cell composition and function. This review summarizes the long-lasting alterations in immunological functions associated with atomic-bomb irradiation, and discusses the likelihood that damaging effects of radiation on the immune system may be involved partly in disease development so frequently observed in A-bomb survivors. Significant immunological alterations noted include: (i) attrition of T-cell functions, as reductions in mitogen-dependent proliferation and interleukin-2 (IL-2) production; (ii) decrease in helper T-cell populations; and (iii) increase in blood inflammatory cytokine levels. These findings suggest that A-bomb radiation exposure perturbed one or more of the primary processes responsible for T-cell homeostasis and the balance between cell renewal and survival and cell death among naive and memory T cells. Such perturbed T-cell homeostasis may result in acceleration of immunological aging. Persistent inflammation, linked in some way to the perturbation of T-cell homeostasis, is key in addressing whether such noted immunological changes observed in A-bomb survivors are in fact associated with disease development.

  17. Long-Lasting LTP Requires Neither Repeated Trains for Its Induction Nor Protein Synthesis for Its Development

    PubMed Central

    Villers, Agnès; Godaux, Emile; Ris, Laurence

    2012-01-01

    Current thinking about LTP triggered in the area CA1 of hippocampal slices is ruled by two “dogmas”: (1) A single train of high-frequency stimulation is sufficient to trigger short-lasting LTP (1 – 3 h), whereas multiple trains are required to induce long-lasting LTP (L-LTP, more than 4 h). (2) The development of the late phase of L-LTP requires the synthesis of new proteins. In this study, we found that a single high-frequency train could trigger an LTP lasting more than 8 h that was not affected by either anisomycin or cycloheximide (two inhibitors of protein synthesis). We ascertained that the induction of this L-LTP made use of the same mechanisms as those usually reported to be involved in LTP induction: it was dependent on NMDA receptors and on the activation of two “core” kinases, CaMKII and PI3K. These findings call into question the two “dogmas” about LTP. PMID:22792408

  18. Generation of a long-lasting, protective, and neutralizing antibody response to the ranavirus FV3 by the frog Xenopus.

    PubMed

    Maniero, Gregory D; Morales, Heidi; Gantress, Jennifer; Robert, Jacques

    2006-01-01

    Xenopus serves as an experimental model to evaluate the contribution of adaptive immunity in host susceptibility to emerging ranaviral diseases that may contribute to amphibian population declines. It has been previously shown that following a secondary infection with the ranavirus frog virus 3 (FV3), adult Xenopus more rapidly clear FV3 and generate specific anti-FV3 IgY antibodies. We have further evaluated the potency and persistence of the Xenopus antibody response against FV3. Frogs inoculated with FV3 (without adjuvant) up to 15 months after priming produce specific, thymus-dependent anti-FV3 IgY antibodies detectable from 10 days to 8 weeks post-infection. These antisera from boosted frogs are neutralizing in vitro and provide partial passive protection to susceptible larvae when they are injected a few minutes before FV3 inoculation. These results with Xenopus suggest that other anuran amphibians are likely to develop effective long-lasting protective humoral immunity after an initial viral exposure.

  19. Influence of long-lasting heat treatments on the structure and properties of the zirconium-steel bond

    NASA Astrophysics Data System (ADS)

    Prażmowski, Mariusz; Paul, Henryk; Najwer, Michał; Pocica, Anna

    2017-10-01

    The explosive welding technology is related to the dynamic impact of the clad onto base material. These results in significant microstructural changes of the bonded materials, the increase of internal stresses and the strain hardening of layers near the interface. In order to eliminate these unfavorable effects, it is advisable to carry out proper heat treatment. The paper presents the results of structural examinations and mechanical properties of bimetal zirconium - carbon steel, after long-lasting heat treatment. Bimetallic samples were annealed at 600oC for 1, 10, 100, 500, 1000 hours. Microscopic examination were used to the analysis of microstructural changes, whereas systematic microhardness measurements and static tensile test to evaluation of the mechanical properties. It was found that the temperature has a beneficial effect on the changes in the bond zone and for longer annealing times a systematic decrease of the strength properties of the tested bimetal was observed. However, essential for the clad mechanical properties changes were observed in carbon steel plate. After short annealing (times of 1h and 10h) only small microstructural changes due to processes of recovery and recrystallization were observed in layers near the interface. The increase of annealing time was conducive to grain growth and carbon diffusion in the interfacial layer from steel towards zirconium.

  20. One session of repeated parietal theta burst stimulation trains induces long-lasting improvement of visual neglect.

    PubMed

    Nyffeler, Thomas; Cazzoli, Dario; Hess, Christian W; Müri, René M

    2009-08-01

    Visual neglect is a frequent disability in stroke and adversely affects mobility, discharge destination, and length of hospital stay. It is assumed that its severity is enhanced by a released interhemispheric inhibition from the unaffected toward the affected hemisphere. Continuous theta burst transcranial magnetic stimulation (TBS) is a new inhibitory brain stimulation protocol which has the potential to induce behavioral effects outlasting stimulation. We aimed to test whether parietal TBS over the unaffected hemisphere can induce a long-lasting improvement of visual neglect by reducing the interhemispheric inhibition. Eleven patients with left-sided visual neglect attributable to right hemispheric stroke were tested in a visual perception task. To evaluate the specificity of the TBS effect, 3 conditions were tested: 2 TBS trains over the left contralesional posterior parietal cortex, 2 trains of sham stimulation over the contralesional posterior parietal cortex, and a control condition without any intervention. To evaluate the lifetime of repeated trains of TBS in 1 session, 4 trains were applied over the contralesional posterior parietal cortex. Two TBS trains significantly increased the number of perceived left visual targets for up to 8 hours as compared to baseline. No significant improvement was found with sham stimulation or in the control condition without any intervention. The application of 4 TBS trains significantly increased the number of perceived left targets up to 32 hours. The new approach of repeating TBS at the same day may be promising for therapy of neglect.

  1. Long-lasting monoaminergic and behavioral dysfunctions in a mice model of socio-environmental stress during adolescence.

    PubMed

    de Lima, A P N; Sandini, T M; Reis-Silva, T M; Massoco, C O

    2017-01-15

    Adolescence is one of the critical periods of development and has great importance to health for an individual as an adult. Stressors or traumatic events during this period are associated with several psychiatric disorders as related to anxiety or depression and cognitive impairments, but whether negative experiences continue to hinder individuals as they age is not as well understood. We determined how stress during adolescence affects behavior and neurochemistry in adulthood. Using an unpredictable paradigm (2 stressors per day for 10days) in Balb/c mice, behavioral, hormonal, and neurochemical changes were identified 20days after the cessation of treatment. Adolescent stress increased motor activity, emotional arousal and vigilance, together with a reduction in anxiety, and also affected recognition memory. Furthermore, decreased serotonergic activity on hippocampus, hypothalamus and cortex, decreased noradrenergic activity on hippocampus and hypothalamus, and increased the turnover of dopamine in cortex. These data suggest behavioral phenotypes associated with emotional arousal, but not depression, emerge after cessation of stress and remain in adulthood. Social-environmental stress can induce marked and long-lasting changes in HPA resulting from monoaminergic neurotransmission, mainly 5-HT activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Human exposure to early morning Anopheles funestus biting behavior and personal protection provided by long-lasting insecticidal nets.

    PubMed

    Moiroux, Nicolas; Damien, Georgia B; Egrot, Marc; Djenontin, Armel; Chandre, Fabrice; Corbel, Vincent; Killeen, Gerry F; Pennetier, Cédric

    2014-01-01

    A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply.

  3. A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats.

    PubMed

    Widjojoatmodjo, Myra N; Boes, Jolande; van Bers, Marleen; van Remmerden, Yvonne; Roholl, Paul J M; Luytjes, Willem

    2010-06-02

    Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (r)RSV and an rRSV lacking the G gene (DeltaG) were constructed based on a clinical RSV isolate (strain 98-25147-X). Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for DeltaG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days. Collectively, the data indicate that a single dose immunization with the highly attenuated DeltaG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since DeltaG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.

  4. Operational Assessment of Long-Lasting Insecticidal Nets by Using an Anopheles Salivary Biomarker of Human–Vector Contact

    PubMed Central

    Noukpo, Mahoutin H.; Damien, Georgia B.; Elanga-N'Dille, Emmanuel; Sagna, André B.; Drame, Papa M.; Chaffa, Evelyne; Boussari, Olayidé; Corbel, Vincent; Akogbéto, Martin; Remoue, Franck

    2016-01-01

    The widespread implementation of long-lasting insecticidal nets (LLINs) is a major intervention method for malaria control. Although the LLINs coverage increases, information available on the physical integrity (PI) of implemented LLINs is incomplete. This study aimed to validate human IgG antibody (Ab) response to Anopheles gSG6-P1 salivary peptide antigen, previously demonstrated as a pertinent biomarker of human exposure to Anopheles bites, for evaluating the PI of LLINs in field conditions. We analyzed data from 262 randomly selected children (< 5 years of age) in health districts of Benin. Anti-gSG6-P1 IgG responses were assessed and compared with the PI of LLINs that these same children slept under, and evaluated by the hole index (HI). Specific IgG levels were positively correlated to LLINs HI (r = 0.342; P < 0.0001). According to antipeptide IgG level (i.e., intensity of vector exposure), two categories of LLINs PI were defined: 1) group “HI: [0, 100]” corresponding to LLINs with “good” PI and 2) “HI > 100” corresponding to LLINs with “bad” PI. These results suggest that human Ab response to salivary peptide could be a complementary tool to help defining a standardized threshold of efficacy for LLINs under field use. PMID:27928087

  5. Real time large scale in vivo observations reveal intrinsic synchrony, plasticity and growth cone dynamics of midline crossing axons during neuronal wiring of the zebrafish spinal cord.

    PubMed

    Andersen, Søren S L

    2017-08-30

    How axons are wired in the vertebrate spinal cord has been studied mostly using fixed samples or looking at individually growing axons. Using light-sheet microscopy, early neural development is here followed in vivo in real time at high resolution along several hundred micrometers of the zebrafish spinal cord. The dynamics and time course of cellular development and axonal wiring of interneurons expressing GFP under control of the dmrt3 promotor are analyzed. Following neurulation, commissural axons are observed crossing the ventral floor plate midline perpendicularly at about 20 microns/h and in a manner dependent on the Robo3 but not the EphA4 receptors. Ipsilateral axons extend concurrently, at three to six times higher growth rates and independently of said receptors. At guidance points, commissural axons are seen to decrease their growth rate and cones increase in size. Commissural filopodia appear on the floor plate to interact with the nascent neural network, and thereby trigger immediate plastic and reversible sinusoidal-shaped bending movements of the neighboring commissural shafts. A 3D reconstruction of the 4 dpf spinal cord demonstrates variable dmrt3 cell body position and dimensions, confirmed by single cell FlowSight analysis, and also a minor second population of commissurals crossing later and more dorsally. The recordings show the strikingly stereotyped spatio-temporal control that governs axonal wiring of the zebrafish spinal cord. The live observations give renewed perspective on the mechanisms of axonal guidance in the spinal cord that provide for a discussion of the current distinction between diffusible long-range versus substrate-bound short-range guidance cues. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  6. Activation of Exchange Protein Activated by Cyclic-AMP Enhances Long-Lasting Synaptic Potentiation in the Hippocampus

    ERIC Educational Resources Information Center

    Gelinas, Jennifer N.; Banko, Jessica L.; Peters, Melinda M.; Klann, Eric; Weeber, Edwin J.; Nguyen, Peter V.

    2008-01-01

    cAMP is a critical second messenger implicated in synaptic plasticity and memory in the mammalian brain. Substantial evidence links increases in intracellular cAMP to activation of cAMP-dependent protein kinase (PKA) and subsequent phosphorylation of downstream effectors (transcription factors, receptors, protein kinases) necessary for long-term…

  7. Maternal effects are long-lasting and influence female offspring's reproductive strategy in the swordtail fish Xiphophorus multilineatus.

    PubMed

    Murphy, A D; Goedert, D; Morris, M R

    2014-08-01

    The adaptive benefits of maternal investment into individual offspring (inherited environmental effects) will be shaped by selection on mothers as well as their offspring, often across variable environments. We examined how a mother's nutritional environment interacted with her offspring's nutritional and social environment in Xiphophorus multilineatus, a live-bearing fish. Fry from mothers reared on two different nutritional diets (HQ=high quality and LQ=low quality) were all reared on a LQ diet in addition to being split between two social treatments: exposed to a large adult male during development and not exposed. Mothers raised on a HQ diet produce offspring that were not only initially larger (at 14 days of age), but grew faster, and were larger at sexual maturity. Male offspring from mothers raised on both diets responded to the exposure to courter males by growing faster; however, the response of their sisters varied with mother's diet; females from HQ diet mothers reduced growth if exposed to a courter male, whereas females from LQ diet mothers increased growth. Therefore, we detected variation in maternal investment depending on female size and diet, and the effects of this variation on offspring were long-lasting and sex specific. Our results support the maternal stress hypothesis, with selection on mothers to reduce investment in low-quality environments. In addition, the interaction we detected between the mother's nutritional environment and the female offspring's social environment suggests that female offspring adopted different reproductive strategies depending on maternal investment. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  8. The effect of long-lasting insecticidal water container covers on field populations of Aedes aegypti (L.) mosquitoes in Cambodia.

    PubMed

    Seng, Chang Moh; Setha, To; Nealon, Joshua; Chantha, Ngan; Socheat, Doung; Nathan, Michael B

    2008-12-01

    Dengue in Cambodia is mainly transmitted by Aedes aegypti (L.) mosquitoes that primarily breed in large, concrete jars (> or =200 liters) used for the storage of water for domestic use. Following a preliminary risk assessment, long-lasting insecticidal netting (LN) treated with deltamethrin was incorporated into the design of the covers for these jars. Their effect on immature and adult female populations of Ae. aegypti in six villages in a peri-urban area of Cambodia were compared with populations in six nearby control villages before and for 22 weeks after distribution of the jar covers. There were significantly fewer pupae per house in intervention villages than in control villages (6.6 and 31.9, respectively, p<0.01). Fewer pupae were recovered from intervention houses than from control houses at every post-intervention assessment. Two weeks after the intervention, the average number of indoor resting female Ae. aegypti per house in the intervention villages had declined approximately three-fold, whereas in the controls there was only a slight reduction (16%). The magnitude of the difference between the two areas diminished over time, which contact bioassays confirmed was likely due to a gradual reduction of insecticidal effect of the jar covers. In the study area, insecticide-treated covers for large concrete water storage jars were efficacious for controlling Ae. aegypti in the protected water jars and with a demonstrable effect on adult densities and survival. Further studies of this targeted container strategy in Cambodia, and elsewhere, are recommended. However, improvements in technology that would extend the duration of insecticidal effectiveness of LN materials may be needed for the development of cost-effective public health applications.

  9. Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity.

    PubMed

    Dunussi-Joannopoulos, K; Runyon, K; Erickson, J; Schaub, R G; Hawley, R G; Leonard, J P

    1999-12-15

    Interleukin-12 (IL-12) is a heterodimeric cytokine mediating a dynamic interplay between T cells and antigen-presenting cells (APCs). Preclinical studies have demonstrated that recombinant murine IL-12 (rmIL-12) promotes specific antitumor immunity mediated by T cells in several types of tumors. However, the in vivo antitumor properties of IL-12 in acute myeloid leukemia (AML) have not been previously reported. We show here in a murine AML model that systemic administration of rmIL-12 significantly delays tumor growth but is incapable of rescuing mice from lethal leukemia. In contrast, AML cells genetically modified to express IL-12 (IL12-AML) using murine stem cell virus (MSCV) p40 + p35 elicit very potent antileukemic activity. Vaccines with lethally irradiated IL12-AML cells protect naive mice against challenge with wild-type AML cells and, more importantly, can cure mice bearing a considerable leukemic burden. Immunized mice show no signs of systemic IL-12 toxicity and their spleen histology is comparable with naive mice spleen. In vivo depletion of IL-12, interferon-gamma (IFN-gamma), or CD8(+) T cells after injections with live IL12-AML cells abrogates completely the antileukemia immune responses. Studies on the in vitro effects of IFN-gamma on AML cells demonstrate enhanced expression of major histocompatibility complex (MHC) and accessory molecules and induction of the costimulatory molecules B7.1 and B7.2, but no significant direct antiproliferative effect. (51)Cr release assays show that rejection of live IL12-AML cells supports the development of long-lasting leukemia-specific cytotoxic T lymphocyte (CTL) activity. In conclusion, our results demonstrate that IL12-AML vaccination is a safe and potent immunotherapeutic approach that has a great potential to eliminate minimal residual disease in patients with AML.

  10. C-547, a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase: Pharmacokinetic and pharmacodynamic studies.

    PubMed

    Petrov, Konstantin; Zueva, Irina; Kovyazina, Irina; Sedov, Igor; Lushchekina, Sofya; Kharlamova, Alexandra; Lenina, Oksana; Koshkin, Sergei; Shtyrlin, Yurii; Nikolsky, Evgeny; Masson, Patrick

    2018-03-15

    C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was intravenously administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of distribution (3800 ml/kg) is 15 times larger than the distribution volume, indicating a good tissue distribution. C-547 is slowly eliminated (k el  = 0.17 h -1 ; T 1/2  = 4 h) from the bloodstream. Effect of C-547 on animal model of myasthenia gravis persists for more than 72 h, even though the drug is not analytically detectable in the blood. A PK/PD model was built to account for such a pharmacodynamical (PD) effect. Long-lasting effect results from micro-PD mechanisms: the slow-binding nature of inhibition, high affinity for AChE and long residence time on target at neuromuscular junction (NMJ). In addition, NMJ spatial constraints i.e. high concentration of AChE in a small volume, and slow diffusion rate of free C-547 out of NMJ, make possible effective rebinding of ligand. Thus, compared to other cholinesterase inhibitors used for palliative treatment of myasthenia gravis, C-547 is the most selective drug, displays a slow pharmacokinetics, and has the longest duration of action. This makes C-547 a promising drug leader for treatment of myasthenia gravis, and a template for development of other drugs against neurological diseases and for neuroprotection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain

    PubMed Central

    Bonnard, Elisabeth; Poras, Hervé; Nadal, Xavier; Maldonado, Rafael; Fournié-Zaluski, Marie-Claude; Roques, Bernard P

    2015-01-01

    The peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain generation as suggested by the modulation of opioid receptors expression and enkephalins (ENKs) release observed in these painful conditions. Accordingly, an innovative approach in the treatment of these nocifensive events is to increase and maintain high local concentrations of extracellular pain-evoked ENKs, by preventing their physiological enzymatic inactivation by two Zn metallopeptidases, the neutral endopeptidase (NEP, neprilysin, EC 3.4.24.11) and the neutral aminopeptidase (APN, EC 3.4.11.2). With this aim, new orally active dual ENKephalinase inhibitors (DENKIs) were designed as soluble prodrugs by introducing a N-terminal cleavable carbamate in the previously described aminophosphinic inhibitors. This induces long-lasting antinociceptive responses after oral administration, in various rodent models of inflammatory and neuropathic pain. These responses are mediated through stimulation of peripheral opioid receptors by DENKIs-protected ENKs as demonstrated by naloxone methiodide reversion. In all tested models, the most efficient prodrug 2a (PL265) was active, at least during 150–180 min, after single oral administration of 25–50 mg/kg in mice and of 100–200 mg/kg in rats. In models of neuropathic pain, both hyperalgesia and allodynia were markedly reduced. Interestingly, combination of inactive doses of 2a (PL265) and of the anti-epileptic drug gabapentin had synergistic effect on neuropathic pain. Pharmacokinetic studies of 2a (PL265) in rats show that the active drug is the only generated metabolite produced. These encouraging results have made 2a (PL265) a suitable candidate for clinical development. PMID:25692029

  12. Challenges for malaria elimination in Zanzibar: pyrethroid resistance in malaria vectors and poor performance of long-lasting insecticide nets

    PubMed Central

    2013-01-01

    Background Long-lasting insecticide treated nets (LLINs) and indoor residual house spraying (IRS) are the main interventions for the control of malaria vectors in Zanzibar. The aim of the present study was to assess the susceptibility status of malaria vectors against the insecticides used for LLINs and IRS and to determine the durability and efficacy of LLINs on the island. Methods Mosquitoes were sampled from Pemba and Unguja islands in 2010–2011 for use in WHO susceptibility tests. One hundred and fifty LLINs were collected from households on Unguja, their physical state was recorded and then tested for efficacy as well as total insecticide content. Results Species identification revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a small number of An. gambiae s.s. and An. merus being present. Susceptibility tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible to all pyrethroids tested. A physical examination of 150 LLINs showed that two thirds were damaged after only three years in use. All used nets had a significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2 compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly against both susceptible An. gambiae s.s. colony mosquitoes and wild-type mosquitoes from Pemba after just six washes (p < 0.001). Conclusion The sustainability of the gains achieved in malaria control in Zanzibar is seriously threatened by the resistance of malaria vectors to pyrethroids and the short-lived efficacy of LLINs. This study has revealed that even in relatively well-resourced and logistically manageable places like Zanzibar, malaria elimination is going to be difficult to achieve with the current control measures. PMID:23537463

  13. Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory

    PubMed Central

    da Costa, Adeliane Castro; Nogueira, Sarah Veloso; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Bacille Calmette–Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG) published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words TB, rBCG vaccine, and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of Mycobacterium tuberculosis (Mtb) immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and overexpression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC:hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory. PMID:24778634

  14. Long-lasting paracrine effects of human cord blood cells on damaged neocortex in an animal model of cerebral palsy.

    PubMed

    Bae, Sang-Hun; Kong, Tae-Ho; Lee, Hyun-Seob; Kim, Kyung-Sul; Hong, Kwan Soo; Chopp, Michael; Kang, Myung-Seo; Moon, Jisook

    2012-01-01

    Neonatal asphyxia is an important contributor to cerebral palsy (CP), for which there is no effective treatment to date. The administration of human cord blood cells (hUCBCs) is emerging as a therapeutic strategy for the treatment of neurological disorders. However, there are few studies on the application of hUCBCs to the treatment of neonatal ischemia as a model of CP. Experiments and behavioral tests (mainly motor tests) performed on neonatal hypoxia/ischemia have been limited to short-term effects of hUCBCs, but mechanisms of action have not been investigated. We performed a study on the use of hUCBCs in a rat model of neonatal hypoxia/ischemia and investigated the underlying mechanism for therapeutic benefits of hUCBC treatment. hUCBCs were intravenously transplanted into a rat model of neonatal hypoxia ischemia. hUCBCs increased microglia temporarily in the periventricular striatum in the early phase of disease, protected mature neurons in the neocortex from injury, paved the way for the near-normalization of brain damage in the subventricular zone (SVZ), and, in consequence, significantly improved performance in a battery of behavioral tests compared to the vehicle-treated group. Although the transplanted cells were rarely observed in the brain 3 weeks after transplantation, the effects of the improved behavioral functions persisted. Our preclinical findings suggest that the long-lasting positive influence of hUCBCs is derived from paracrine effects of hUCBCs that stimulate recovery in the injured brain and protect against further brain damage.

  15. Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats.

    PubMed

    Wang, Zhiqiang; Fan, Jin; Wang, Jian; Li, Yuxia; Duan, Dan; Du, Guo; Wang, Qingsong

    2016-03-15

    Synaptic dysfunction underlies cognitive deficits induced by chronic cerebral hypoperfusion (CCH). There are silent synapses in neural circuits, but the effect of CCH on silent synapses is unknown. The present study was designed to explore learning and memory deficits and dynamic changes in silent synapses by direct visualization in a rat model of CCH. Adult male Sprague-Dawley rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) to reproduce CCH. Learning and memory effects were examined at 1, 4, 12, and 24 weeks after BCCAO. In addition, immunofluorescent confocal microscopy was used to detect AMPA and N-methyl-d-aspartate receptors colocalized with synaptophysin, and Golgi-Cox staining was used to observe dendritic spine density. We found that BCCAO rats exhibited recognition memory deficits from 4 weeks; spatial learning and memory, as well as working memory impairment began at 1 week and persistent to 24 weeks after surgery. Following BCCAO, the percentage of silent synapses increased by 29.81-55.08% compared with the controls at different time points (P<0.001). Compared with control groups, dendritic spine density in the CA1 region of BCCAO groups significantly decreased (P<0.001). Thus, the present study suggests that CCH can induce long-lasting cognitive deficits and long-term increase in the number of silent synapses. Furthermore, the decrease in dendritic spine density was correlated with the decrease in the number of functional synapses. The results suggest a potential mechanism by which CCH can induce learning and memory deficits. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. CRF2 Receptor Deficiency Eliminates the Long-Lasting Vulnerability of Motivational States Induced by Opiate Withdrawal

    PubMed Central

    Morisot, Nadège; Rouibi, Khalil; Contarino, Angelo

    2015-01-01

    Vulnerability to stressful life events is a hallmark of drug dependence that may persist long after cessation of drug intake and dramatically fuel key clinical features, such as deregulated up-shifted motivational states and craving. However, to date, no effective therapy is available for reducing vulnerability to stressful events in former drug users and drug-dependent patients, mostly because of poor knowledge of the mechanisms underlying it. In this study, we report that genetic inactivation of the stress-responsive corticotropin-releasing factor receptor-2 (CRF2−/−) completely eliminates the reemergence of increased nonrewarded nose-pokes, reflecting up-shifted motivational states, triggered by ethological environmental stressors long after cessation of morphine administration in mice. Accordingly, CRF2 receptor deficiency completely abolishes the increase in biomarkers of synthesis of major brain motivational substrates, such as ventral tegmental area (VTA) dopamine (DA) and amygdala γ-aminobutyric acid (GABA) systems, associated with the stress-induced reemergence of up-shifted motivational states long after opiate withdrawal. Nevertheless, neither CRF2 receptor deficiency nor long-term opiate withdrawal affects amygdala CRF or hypothalamus CRF expression, indicating preserved brain stress-coping systems. Moreover, CRF2 receptor deficiency does not influence the locomotor or the anxiety-like effect of long-term opiate withdrawal. Thus, the present results reveal an essential and specific role for the CRF2 receptor in the stress-induced reemergence of up-shifted motivational states and related alterations in brain motivational systems long after opiate withdrawal. These findings suggest new strategies for the treatment of the severe and long-lasting vulnerability that inexorably follows drug withdrawal and hinder drug abstinence. PMID:25672976

  17. Maintenance of demographic and hematological profiles in a long-lasting dengue fever outbreak: implications for management.

    PubMed

    Dos Santos Carmo, Andréia Moreira; Suzuki, Rodrigo Buzinaro; Riquena, Michele Marcondes; Eterovic, André; Sperança, Márcia Aparecida

    2016-09-05

    Dengue fever (DF) outbreaks present regionally specific epidemiological and clinical characteristics. In certain medium-sized cities (100 000-250 000 inhabitants) of São Paulo State, Brazil, and after reaching an incidence of 150 cases/100 000 inhabitants ("epidemiological threshold"), clinical diagnosis indicated dengue virus (DENV) infection. During this period, other seasonally infectious diseases with symptoms and physical signs mimicking DF can simultaneously occur, with the consequential overcrowding of health care facilities as the principal drawbacks. Confirmation of clinical diagnosis of DF with serological tests may help in avoiding faulty diagnosis in patients, who might later undergo dengue hemorrhagic fever (DHF) and the dengue-shock syndrome (DSS). Furthermore, demographic and hematological profiles of patients are useful in detecting specific early characteristics associated to DF, DHF and DSS. From March to June, 2007, 456 patients from Marilia in northwest São Paulo State who had only been diagnosed for DF by clinical criteria, underwent serologic testing for non-structural 1 (NS1) DENV antigens. Individual results were used in comparative analysis according to demographic (gender, age) and hematological (leukocyte and platelet counts, percentage of atypical lymphocytes) profiles. Temporal patterns were evaluated by subdividing data according to time of initial attendance, using recorded variables as predictors of DENV infection in logistic regression models and ROC curves. Serologic DENV detection was positive in 70.6 % of the patients. Lower leukocyte and platelet counts were the most important factors in predicting DENV infection (respective medians DENV + = 3 715 cells/ml and DENV- = 6 760 cells/ml, and DENV + = 134 896 cells/ml and DENV- = 223 872 cells/ml). Furthermore, all demographic and hematological profiles presented a conservative temporal pattern throughout this long-lasting outbreak. As consistency throughout

  18. Long lasting preventive effects of piperlongumine and a Piper longum extract against stress triggered pathologies in mice.

    PubMed

    Yadav, Vaishali; Chatterjee, Shyam Sunder; Majeed, Muhammed; Kumar, Vikas

    2015-01-01

    To compare doxycycline (DOX) such as oral efficacies of piperlongumine (PL) and a Piper longum fruits extract (PLE) as stress resistance inducers. Efficacies of oral pretreatments with 5 mg/kg PL or PLE or of 50 mg/kg DOX for 10 consecutive days against stress resistance were compared. Mice in treated groups were subjected to a stress induced hyperthermia on the 1(st), 5(th), 7(th), and 10(th)day. Treated mice were then subjected to tail suspension test on the 11(th)day. Alteration in body weights, core temperatures, and gastric ulcers triggered by occasional exposures to foot shocks were determined. DOX like long-lasting protective effects of PL and PLE against gradual alterations in body weights, basal temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed 1 day after the last foot-shock exposures and gastric ulcers and other pathologies quantified 1 day after the test were also suppressed in PL or PLE or DOX pretreated groups. PL and crude PLE are DOX like long-acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of P. longum and other plants of the Piperaceae family, and reveal that PL is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant-derived products enriched in PL or piperine like amide alkaloids in volunteers and patients can be warranted.

  19. Low long-lasting insecticide nets (LLINs) use among household members for protection against mosquito bite in Kersa, Eastern Ethiopia.

    PubMed

    Gobena, Tesfaye; Berhane, Yemane; Worku, Alemayehu

    2012-10-29

    In Ethiopia, despite the increasing availability of long-lasting insecticide treated nets (LLINs), the LLINs use among LLINs owning households has not been satisfactory. Identifying the circumstances and the associated factors is necessary to achieve the Millennium Development Goal targets. We aimed to assess barriers related with LLIN use at the household level. A cross sectional survey was conducted in Kersa Demographic Surveillance and Health Research Center (KDS-HRC) from October to November 2010. A total of 2867 households were selected from a surveillance database using a simple random sampling technique. The data were collected by interviewing women, direct observation of LLINs conditions and use, and in-depth interviewing of key informants. Multivariate analysis was used to determine independent predictors of LLIN non-use. Of the total surveyed households, 65.5% (1879) had at least one LLIN, but 33.5% (630) LLINs owned households had used at least one LLIN the night before the survey. Low educational level of women, low awareness on malaria prevention, unavailability of separate sleeping room, LLIN colour preference, and unavailability of enough LLINs to the household members were the main barriers to LLIN use. A supplementary qualitative interview with key informants also identified that poor condition of LLINs; undermining the extent of malaria; and using the LLIN for other purposes as the main reasons for non-use. This study indicates that only about one third of LLIN owned households are actually using at least one LLIN for protection against mosquito bite. Thus, majority of the residents are at higher risk of mosquito bite and acquiring of malaria infection. Households living in fringe zone are not benefiting from the LLIN protection. Further progress in malaria prevention can be achieved by specifically targeting populations in fringe zones and conducting focused public education to increase LLIN use.

  20. To assess whether addition of pyriproxyfen to long-lasting insecticidal mosquito nets increases their durability compared to standard long-lasting insecticidal mosquito nets: study protocol for a randomised controlled trial.

    PubMed

    Sagnon, N'Fale; Pinder, Margaret; Tchicaya, Emile Fs; Tiono, Alfred B; Faragher, Brian; Ranson, Hilary; Lindsay, Steve W

    2015-04-28

    The effectiveness of pyrethroid-treated bednets for malaria control in sub-Saharan Africa is under threat because of high levels of resistance to pyrethroid insecticides in the vectors. Here we assess the durability of polyethylene nets with a novel combination of permethrin, a pyrethroid, with pyriproxyfen, an insect juvenile mimic (PPF-LLIN), in comparison with a typical permethrin-treated long-lasting insecticidal net (LLIN). This is a cluster randomised controlled trial of net durability in Burkina Faso, with clustering at the level of the compound and includes entomological outcome measurements. Half the compounds in each village will be randomly allocated PPF-LLIN and half the LLIN. All sleeping places in a compound will be provided with one type of net. We will distribute the nets at the start of the first transmission season and follow net use at the start and end of each transmission season for 3 years. In one village, bio-efficacy and chemical content will be recorded immediately after net distribution and then at 6, 12, 18, 24, 30 and 36 months. In the other village net survivorship and fabric integrity will be recorded immediately after distribution, and then at 6, 12, 18, 24, 30 and 36 months. Routine measurements of indoor temperature and relative humidity will be made in both villages during the study. Residents will be followed for possible side effects of the PPF-LLIN by surveillance of known asthmatic subjects during the first month post-distribution and pregnancy outcomes will be monitored from antenatal clinic records. The protocol is novel on two accounts. Firstly, it is the first to describe the procedure for measuring net durability following recent World Health Organisation (WHO) guidelines. Meeting the minimum requirements set in the guidelines is essential before a new type of net can be recommended by WHO's Pesticide Evaluation Scheme (WHOPES). Secondly, it describes methods to monitor the persistence of an active ingredient that reduces

  1. Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild RodentsProechimysfrom 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

    that LTP decays rapidly over time reaching basal levels at 90 min after theta-burst stimulation in Proechimys , contrasting to the stable LTP found in the Wistar rats which was observed throughout 3-h recording period. These findings suggest a link between the LTP decay and the lack of 24-h long-lasting memory process in Proechimys . Nevertheless, why early-phase LTP in Proechimys decays very rapidly remains to be elucidated.

  2. Maternal stress during late gestation has moderate but long-lasting effects on the immune system of the piglets.

    PubMed

    Couret, David; Jamin, Agnès; Kuntz-Simon, Gaëlle; Prunier, Armelle; Merlot, Elodie

    2009-09-15

    Events acting prenatally on developing foetuses are important determinants for disorders later in life. Prenatal stress (PNS) is one of these events. The purpose of this study was to determine the consequences of a repeated social stress applied during late gestation of the pregnant gilt on the immune system and hypothalamo-pituitary-adrenal (HPA) axis activity of the piglets from birth to two months of age. Pregnant gilts were submitted to repeated social stress which was induced by housing unfamiliar gilts in pairs modified twice a week during 4 weeks between days 77 and 105 of gestation (S group, n=18). Control gilts were housed in stable pairs during the same period (C group, n=18). Blood cortisol, haptoglobin and IgG levels, immune cell counts, mitogen-induced whole-blood proliferation and TNF-alpha production were evaluated in piglets at 4 days of age (D4), before and after weaning (D26 and 28) and before and after relocation to a new building (D60 and 62). We found that PNS did not affect growth rate of the progeny. It decreased the relative weight of adrenal glands on D4 (P<0.05) but plasma cortisol levels were similar in both groups at all ages. IgG levels in colostrum and in the serum of piglets were not affected. PNS decreased the total numbers of white blood cells, lymphocytes and granulocytes from D26 to D60 (P<0.05), the CD4(+)/CD8(+) T cell ratio on D4 (P<0.05), and LPS induced-TNF-alpha production on D60 (P<0.05). PNS increased the ConA-induced lymphocyte proliferation on D4 and D60 and the PWM-induced proliferation on D60 (P<0.05). Our results demonstrate that a repeated social stress applied to pregnant sows during late gestation can induce long-lasting effects on several parameters of the immune function of the offspring. These effects are not due to modifications of the HPA axis activity and may impair the abilities of the piglets to efficiently react against infections during the suckling period and around weaning.

  3. Evaluation of the association between long-lasting insecticidal nets mass distribution campaigns and child malaria in Nigeria.

    PubMed

    Kyu, Hmwe Hmwe; Georgiades, Katholiki; Shannon, Harry S; Boyle, Michael H

    2013-01-09

    Nigeria carries the greatest malaria burden among countries in the world. As part of the National Malaria Control Strategic Plan, free long-lasting insecticidal nets (LLINs) were distributed in 14 states of Nigeria through mass campaigns led by different organizations (the World Bank, UNICEF, or the Global Fund) between May 2009 and August 2010. The objective of this study was to evaluate the association between LLIN distribution campaigns and child malaria in Nigeria. Data were from the Nigeria Malaria Indicator Survey which was carried out from October to December 2010 on a nationally representative sample of households. Participants were women aged 15-49 years and their children aged less than five years (N = 4082). The main outcome measure was the presence or absence of malaria parasites in blood samples of children (6-59 months). Compared with children living in communities with no campaigns, those in the campaign areas were less likely to test positive for malaria after adjusting for geographic locations, community- and individual-level characteristics including child-level use of insecticide-treated nets (ITNs). The protective effects were statistically significant for the World Bank Booster Project areas (OR = 0.18, 95% CI = 0.04-0.73) but did not reach statistical significance for other campaign areas. Results also showed that community-level wealth (OR = 0.51, 95% CI = 0.34-0.76), community-level maternal knowledge regarding malaria prevention (OR = 0.70, 95% CI = 0.50-0.97), and child-level use of ITNs (OR = 0.79, 95% CI = 0.63-0.99) were negatively associated with child malaria. The observed protective effects on child malaria of these campaigns (statistically significant in the World Bank Booster Project areas and non-significant in the other areas) need to be corroborated by future effectiveness studies. Results also show that improving community-level maternal knowledge through appropriate channels might be helpful

  4. Robotic guidance induces long-lasting changes in the movement pattern of a novel sport-specific motor task.

    PubMed

    Kümmel, Jakob; Kramer, Andreas; Gruber, Markus

    2014-12-01

    Facilitating the learning or relearning of motor tasks is one of the main goals of coaches, teachers and therapists. One promising way to achieve this goal is guiding the learner through the correct movement trajectory with the help of a robotic device. The aim of this study was to investigate if haptic guidance can induce long-lasting changes in the movement pattern of a complex sport-specific motor task. For this purpose, 31 subjects were assigned to one of three groups: EA (early angle, n=10), LA (late angle, n=11) and CON (control, n=10). EA and LA successfully completed five training sessions, which consisted of 50 robot-guided golf swings and 10 free swings each, whereas CON had no training. The EA group was guided through the movement with the wrist being bent early during backswing, whereas in the LA group it was bent late. The participants of EA and LA were not told about this difference in the movement patterns. To assess if the robot-guided training was successful in shaping the movement pattern, the timing of the wrist bending during the backswing in free swings was measured before (PRE), one day after (POST), and 7 days after (FUP) the five training sessions. The ANOVA (time×group×angle) showed that during POST and FUP, the participants of the EA group bent their wrist significantly earlier during the backswing than the other groups. Post-hoc analyses revealed that this interaction effect was mainly due to the differences in the wrist angle progression during the first 5° of the backswing. The robot-guided training was successful in shaping the movement pattern, and these changes persisted even after 7 days without further practice. This might have implications for the learning of complex motor tasks in general, as haptic guidance might quickly provide the beginner with an internal model of the correct movement pattern without having to direct the learner's attention towards the key points of the correct movement pattern. Copyright © 2014 Elsevier

  5. Analysing and recommending options for maintaining universal coverage with long-lasting insecticidal nets: the case of Tanzania in 2011

    PubMed Central

    2013-01-01

    Background Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or “Keep-Up” distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Methods Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. Results LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of $449 million USD and ensure

  6. Costs and effects of two public sector delivery channels for long-lasting insecticidal nets in Uganda.

    PubMed

    Kolaczinski, Jan H; Kolaczinski, Kate; Kyabayinze, Daniel; Strachan, Daniel; Temperley, Matilda; Wijayanandana, Nayantara; Kilian, Albert

    2010-04-20

    In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda. Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used. After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani. Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among

  7. Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury.

    PubMed

    McPherson, Jacob G; Miller, Robert R; Perlmutter, Steve I

    2015-09-29

    Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural-computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury.

  8. Allergic contact dermatitis caused by (meth)acrylates in long-lasting nail polish - are we facing a new epidemic in the beauty industry?

    PubMed

    Gatica-Ortega, Maria-Elena; Pastor-Nieto, Maria-Antonia; Mercader-García, Pedro; Silvestre-Salvador, Juan-Francisco

    2017-12-01

    Allergic contact dermatitis (ACD) caused by (meth)acrylates has been described both in occupational and in non-occupational settings. To evaluate the clinical patterns, the most frequent allergens and the prognosis in patients sensitized to (meth)acrylates in long-lasting nail polish. The files of patients with ACD caused by (meth)acrylates in long-lasting nail polish diagnosed between January 2013 and June 2016 in four dermatology departments in Spain were reviewed. Patients were followed up by telephone interview. Overall, 2353 patients were patch tested. Forty-three (1.82%) were diagnosed with ACD caused by (meth)acrylates in long-lasting nail polish during that period; all were female, and all had hand dermatitis. Patients were mostly less than 40 years old (72.1%), non-atopic (95.4%) and had an occupational cause of their dermatitis (93%), which developed ∼10.1 months after they had started to use this technique. The most frequent positive allergens were: 2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, and tetrahydrofurfuryl methacrylate. Eight of the 22 interviewed patients were able to improve their working technique and used 4H® protective material (fingerstalls/gloves). Long-lasting nail polishes have become widespread, and it is a matter of concern that we may be facing a new epidemic of ACD caused by these. Policies regulating their use are urgently needed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Palatable Hyper-Caloric Foods Impact on Neuronal Plasticity

    PubMed Central

    Morin, Jean-Pascal; Rodríguez-Durán, Luis F.; Guzmán-Ramos, Kioko; Perez-Cruz, Claudia; Ferreira, Guillaume; Diaz-Cintra, Sofia; Pacheco-López, Gustavo

    2017-01-01

    Neural plasticity is an intrinsic and essential characteristic of the nervous system that allows animals “self-tuning” to adapt to their environment over their lifetime. Activity-dependent synaptic plasticity in the central nervous system is a form of neural plasticity that underlies learning and memory formation, as well as long-lasting, environmentally-induced maladaptive behaviors, such as drug addiction and overeating of palatable hyper-caloric (PHc) food. In western societies, the abundance of PHc foods has caused a dramatic increase in the incidence of overweight/obesity and related disorders. To this regard, it has been suggested that increased adiposity may be caused at least in part by behavioral changes in the affected individuals that are induced by the chronic consumption of PHc foods; some authors have even drawn attention to the similarity that exists between over-indulgent eating and drug addiction. Long-term misuse of certain dietary components has also been linked to chronic neuroimmune maladaptation that may predispose individuals to neurodegenerative conditions such as Alzheimer’s disease. In this review article, we discuss recent evidence that shows how consumption of PHc food can cause maladaptive neural plasticity that converts short-term ingestive drives into compulsive behaviors. We also discuss the neural mechanisms of how chronic consumption of PHc foods may alter brain function and lead to cognitive impairments, focusing on prenatal, childhood and adolescence as vulnerable neurodevelopmental stages to dietary environmental insults. Finally, we outline a societal agenda for harnessing permissive obesogenic environments. PMID:28261067

  10. Aedes aegypti (Diptera: Culicidae): evaluation of natural long-lasting materials containing pyriproxyfen to improve control strategies.

    PubMed

    Seccacini, Emilia; Juan, Laura; Zerba, Eduardo; Licastro, Susana

    2014-09-01

    Natural materials such as beeswax or a paraffin/stearin mixture containing pyriproxyfen and used as a slow release formulation may convert any breeding place into a larvicidal ovitrap for Aedes aegypti (L.) control. Effectiveness and residual activity of beeswax and paraffin/stearin 1:1 discs containing from 10(-5) to 10(-1) % pyriproxyfen and sticked at the bottom of plastic jars were evaluated for adult emergence inhibition (EI) on late 3rd or early 4th instar A. aegypti larvae. At the initial time t = 0, the EI was 100% for vessels containing beeswax or paraffin/stearin 1:1 discs containing up to 10(-4)% pyriproxyfen. For the lowest pyriproxyfen concentration of 10(-5)%, paraffin/stearin mixture gave a higher EI% value than beeswax (100 and 50%, respectively). Jars were kept at room temperature, and water was totally replaced every 15 days. Bioassays for residual activity repeated monthly showed that at 30 days and for pyriproxyfen 10(-5) % and both matrices, the EI values were low and comparable to control values. For pyriproxyfen 10(-4) %, EI remained above 95% for at least 90 days and around 75% up to 180 days. The EI values are always higher for paraffin/stearin mixture than for beeswax. For all other higher concentrations, 100% EI was obtained at least during 300 days. In a semi-field trial, paraffin/stearin/sand O-rings (2:1:2), containing pyriproxyfen 1%, were sunken in 200-l water-storage tanks and held outdoors in a shadow place. After 72 h, a 250-ml aliquot was taken (t = 0) obtaining 100 % EI. Water level was completed to 200 l every 15 days and bioassays repeated monthly as before. Residual activity remains with 100% EI at least for 6 months.

  11. Intrinsic n

    SciTech Connect

    Zhang, S. B.; Wei, S.-H.; Zunger, Alex

    2001-02-15

    ZnO typifies a class of materials that can be doped via native defects in only one way: either n type or p type. We explain this asymmetry in ZnO via a study of its intrinsic defect physics, including Zn{sub O}, Zn{sub i}, V{sub O}, O{sub i}, and V{sub Zn} and n-type impurity dopants, Al and F. We find that ZnO is n type at Zn-rich conditions. This is because (i) the Zn interstitial, Zn{sub i}, is a shallow donor, supplying electrons; (ii) its formation enthalpy is low for both Zn-rich and O-rich conditions, so this defect is abundant; and (iii)more » the native defects that could compensate the n-type doping effect of Zn{sub i} (interstitial O, O{sub i}, and Zn vacancy, V{sub Zn}), have high formation enthalpies for Zn-rich conditions, so these ''electron killers'' are not abundant. We find that ZnO cannot be doped p type via native defects (O{sub i},V{sub Zn}) despite the fact that they are shallow (i.e., supplying holes at room temperature). This is because at both Zn-rich and O-rich conditions, the defects that could compensate p-type doping (V{sub O},Zn{sub i},Zn{sub O}) have low formation enthalpies so these ''hole killers'' form readily. Furthermore, we identify electron-hole radiative recombination at the V{sub O} center as the source of the green luminescence. In contrast, a large structural relaxation of the same center upon double hole capture leads to slow electron-hole recombination (either radiative or nonradiative) responsible for the slow decay of photoconductivity.« less

  12. Effect of the type and number of washes in the efficacy of long lasting insecticidal nets for Aedes aegypti control in Girardot, Colombia.

    PubMed

    García, Diana; Alcalá, Lucas; Quintero, Juliana; Cortés, Sebastián; Brochero, Helena; Carrasquilla, Gabriel

    2017-03-29

    The use of long lasting insecticidal materials has shown promising results in the control of Aedes aegypti. To evaluate the efficacy of long-lasting insecticidal nets (PermaNet®) for Aedes aegypti control after three washing treatments in the city of Girardot, Colombia. Standard bioassays were conducted with the nets following the World Health Organization protocols using wild A. aegypti after three washing treatments: (1) Detergent powder, (2) detergent powder and bleach, and (3) bar soap, until completing 20 washes. The type and number of wash treatments had a significant effect on net efficacy. Greater effects in the insecticide bioavailability were seen for the bar soap treatment. After six washes, mortality decreased by 50% (25/50), vs 66% (33/50) for the detergent powder and 84% (42/50) for the detergent powder and bleach treatments. Regarding the number of washes, the bar soap treatment reduced the efficacy to 68% after only three washes. The effectiveness of long-lasting insecticidal nets (PermaNet 2.0) for A. aegypti control varied in relation to the treatment and number of washes. The bar soap treatment resulted in the greatest reduction of mortality. Further studies on insecticidal reductions are needed under local conditions.

  13. Self-help and self-help groups for people with long-lasting health problems or mental health difficulties in a Nordic context: a review.

    PubMed

    Aglen, Bjørg; Hedlund, Marianne; Landstad, Bodil J

    2011-12-01

    The aim of this review is to provide systematic knowledge of research from Nordic countries about the meaning of self-help and self-help groups when these are used as a concept or method addressing issues related to long-lasting health problems or mental health difficulties. Included were studies conducted in the Nordic countries that were published between January 1999 and September 2009. These studies investigated self-help and self-help groups addressing issues related to long-lasting health problems. A total of 83 publications met the inclusion criteria. Four major characteristics of self-help were found to be present in the publications: self-help as an intrapsychological process, self-help as an interpsychological or group process, self-help as a coping, individual learning or empowerment process, and self-help as an alternative or complement to medical treatment. Of the 83 studies, 72 publications used a professional treatment perspective for studying self-help and 11 publications used a perspective derived from alternative or complementary therapies. The review shows that most of the research on self-help and self-help groups for people with long-lasting health problems or disability is conducted with an interest to improve the professional healthcare system. That is, the health-promotion strategy is mainly considered in the framework of treatment or care settings. This means that self-help in this context does not challenge the dominant biomedical health model.

  14. In Vivo and Ex Vivo Imaging Reveals a Long-Lasting Chlamydial Infection in the Mouse Gastrointestinal Tract following Genital Tract Inoculation

    PubMed Central

    Zhang, Qi; Huang, Yumeng; Gong, Siqi; Yang, Zhangsheng; Sun, Xin; Schenken, Robert

    2015-01-01

    Intravaginal infection with Chlamydia muridarum in mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected with C. trachomatis. Here, we utilized in vivo imaging of C. muridarum infection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. Unexpectedly, the C. muridarum-derived signal was still detectable in the abdominal area 100 days after inoculation. Ex vivo imaging of the mouse organs revealed that the long-lasting presence of the chlamydial signal was restricted to the gastrointestinal (GI) tract, which was validated by directly measuring the chlamydial live organisms and genomes in the same organs. The C. muridarum organisms spreading from the genital to the GI tracts were detected in different mouse strains and appeared to be independent of oral or rectal routes. Mice prevented from orally taking up excretions also developed the long-lasting GI tract infection. Inoculation of C. muridarum directly into the upper genital tract, which resulted in a delayed vaginal shedding of live organisms, accelerated the chlamydial spreading to the GI tract. Thus, we have demonstrated that the genital tract chlamydial organisms may use a systemic route to spread to and establish a long-lasting infection in the GI tract. The significance of the chlamydial spreading from the genital to GI tracts is discussed. PMID:26099591

  15. Long-lasting effects of neck muscle vibration and contraction on self-motion perception of vestibular origin.

    PubMed

    Pettorossi, Vito Enrico; Panichi, Roberto; Botti, Fabio Massimo; Biscarini, Andrea; Filippi, Guido Maria; Schieppati, Marco

    2015-10-01

    previously experienced position of head with respect to trunk. Tonic proprioceptive inflow, as might occur as a consequence of enduring or permanent head postures, can induce adaptive plastic changes in vestibular-dependent motion sensitiveness. These changes might be counteracted by vibration of selected neck muscles. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Cellular Plasticity for Group I mGluR-Mediated Epileptogenesis

    PubMed Central

    Bianchi, Riccardo; Chuang, Shih-Chieh; Zhao, Wangfa; Young, Steven R.; Wong, Robert K.S.

    2009-01-01

    Stimulation of group I metabotropic glutamate receptors (mGluRs) by the agonist (S)-dihydroxyphenylglycine (DHPG) in the hippocampus transforms normal neuronal activity into prolonged epileptiform discharges. The conversion is long-lasting in that epileptiform discharges persist following washout of the inducing agonist and serves as a model of epileptogenesis. The group I mGluR model of epileptogenesis took on special significance because epilepsy associated with fragile X syndrome (FXS) may be caused by excessive group I mGluR signaling. At present, the plasticity mechanism underlying the group I mGluR-mediated epileptogenesis is unknown. ImGluR(V), a voltage-gated cationic current activated by group I mGluR agonists in CA3 pyramidal cells in the hippocampus, is a possible candidate. ImGluR(V) activation is associated with group I mGluR agonist-elicited epileptiform discharges. For ImGluR(V) to play a role in epileptogenesis, long-term activation of the current must occur following group I mGluR agonist exposure or synaptic stimulation. We observed that ImGluR(V), once induced by group I mGluR agonist stimulation in CA3 pyramidal cells, remained undiminished for hours following agonist washout. In slices prepared from FXS model mice, repeated stimulation of recurrent CA3 pyramidal cell synapses, effective in eliciting mGluR-mediated epileptiform discharges, also induced long-lasting ImGluR(V) in CA3 pyramidal cells. Similar to group I mGluR-mediated prolonged epileptiform discharges, persistent ImGluR(V) was no longer observed in preparations pretreated with inhibitors of tyrosine kinase, of extracellular signal-regulated kinase (ERK) 1/2, or of mRNA protein synthesis. The results indicate that ImGluR(V) is an intrinsic plasticity mechanism associated with group I mGluR-mediated epileptogenesis. PMID:19295155

  17. Non-occupational allergic contact dermatitis caused by long-lasting nail polish kits for home use: 'the tip of the iceberg'.

    PubMed

    Gatica-Ortega, María-Elena; Pastor-Nieto, María-Antonia; Gil-Redondo, Rocío; Martínez-Lorenzo, Elena-Remedios; Schöendorff-Ortega, Cristina

    2018-01-12

    Allergic contact dermatitis (ACD) from (meth)acrylates caused by long lasting nail polish (also known as "permanent", "semi-permanent" or "gel nail polish") has been described both in occupational and non-occupational settings. Inexpensive kits for home use have been available for purchase in many stores or through the Internet. To report on several further cases of consumers sensitised to these nail products. Patch test results and evaluation of ingredient labelling of products brought in by the patients. Four new cases are presented. Three of the patients reacted to 2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate and ethyleneglycol dimethacrylate (EGDMA), and all 4 to 2-hydroxy ethylacrylate. Acrylates are present in a wide range of products including medical materials. Sensitization from (meth)acrylates caused by a merely aesthetic procedure might eventually significantly impact health by jeopardizing access to several types of medical interventions. Policies should be implemented restricting the use of long-lasting nail polishes to qualified professionals and banning the indiscriminate sale of kits for home use. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. A Longitudinal Hepatitis B Vaccine Cohort Demonstrates Long-lasting Hepatitis B Virus (HBV) Cellular Immunity Despite Loss of Antibody Against HBV Surface Antigen

    PubMed Central

    Simons, Brenna C.; Spradling, Philip R.; Bruden, Dana J. T.; Zanis, Carolyn; Case, Samantha; Choromanski, Tammy L.; Apodaca, Minjun; Brogdon, Hazel D.; Dwyer, Gaelen; Snowball, Mary; Negus, Susan; Bruce, Michael G.; Morishima, Chihiro; Knall, Cindy; McMahon, Brian J.

    2016-01-01

    Background. Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined. Methods. We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31). Results. All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor α, interleukin 10, or interleukin 6 production by HBV surface antigen–specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection. Conclusions. Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years. PMID:27056956

  19. Fragile X mental retardation protein and synaptic plasticity

    PubMed Central

    2013-01-01

    Loss of the translational repressor FMRP causes Fragile X syndrome. In healthy neurons, FMRP modulates the local translation of numerous synaptic proteins. Synthesis of these proteins is required for the maintenance and regulation of long-lasting changes in synaptic strength. In this role as a translational inhibitor, FMRP exerts profound effects on synaptic plasticity. PMID:23566911

  20. Progress in neural plasticity.

    PubMed

    Zhang, XiaoHui; Poo, Mu-Ming

    2010-03-01

    One of the properties of the nervous system is the use-dependent plasticity of neural circuits. The structure and function of neural circuits are susceptible to changes induced by prior neuronal activity, as reflected by short- and long-term modifications of synaptic efficacy and neuronal excitability. Regarded as the most attractive cellular mechanism underlying higher cognitive functions such as learning and memory, activity-dependent synaptic plasticity has been in the spotlight of modern neuroscience since 1973 when activity-induced long-term potentiation (LTP) of hippocampal synapses was first discovered. Over the last 10 years, Chinese neuroscientists have made notable contributions to the study of the cellular and molecular mechanisms of synaptic plasticity, as well as of the plasticity beyond synapses, including activity-dependent changes in intrinsic neuronal excitability, dendritic integration functions, neuron-glia signaling, and neural network activity. This work highlight some of these significant findings.

  1. Quantifying the relationship between PM2.5 concentration, visibility and planetary boundary layer height for long-lasting haze and fog-haze mixed events in Beijing

    NASA Astrophysics Data System (ADS)

    Luan, Tian; Guo, Xueliang; Guo, Lijun; Zhang, Tianhang

    2018-01-01

    Air quality and visibility are strongly influenced by aerosol loading, which is driven by meteorological conditions. The quantification of their relationships is critical to understanding the physical and chemical processes and forecasting of the polluted events. We investigated and quantified the relationship between PM2.5 (particulate matter with aerodynamic diameter is 2.5 µm and less) mass concentration, visibility and planetary boundary layer (PBL) height in this study based on the data obtained from four long-lasting haze events and seven fog-haze mixed events from January 2014 to March 2015 in Beijing. The statistical results show that there was a negative exponential function between the visibility and the PM2.5 mass concentration for both haze and fog-haze mixed events (with the same R2 of 0.80). However, the fog-haze events caused a more obvious decrease of visibility than that for haze events due to the formation of fog droplets that could induce higher light extinction. The PM2.5 concentration had an inversely linear correlation with PBL height for haze events and a negative exponential correlation for fog-haze mixed events, indicating that the PM2.5 concentration is more sensitive to PBL height in fog-haze mixed events. The visibility had positively linear correlation with the PBL height with an R2 of 0.35 in haze events and positive exponential correlation with an R2 of 0.56 in fog-haze mixed events. We also investigated the physical mechanism responsible for these relationships between visibility, PM2.5 concentration and PBL height through typical haze and fog-haze mixed event and found that a double inversion layer formed in both typical events and played critical roles in maintaining and enhancing the long-lasting polluted events. The variations of the double inversion layers were closely associated with the processes of long-wave radiation cooling in the nighttime and short-wave solar radiation reduction in the daytime. The upper-level stable

  2. Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments.

    PubMed

    Hope, B T; Nye, H E; Kelz, M B; Self, D W; Iadarola, M J; Nakabeppu, Y; Duman, R S; Nestler, E J

    1994-11-01

    Following chronic cocaine treatment, we have found a long-lasting increase in AP-1 binding in the rat nucleus accumbens and striatum, two important targets of the behavioral effects of cocaine. This increase develops gradually over several days and remains at 50% of maximal levels 7 days after the last cocaine exposure. Supershift experiments, along with one- and two-dimensional Western blots, indicate that this chronic AP-1 complex contains at least four Fos-related antigens (FRAs), some of which display delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same chronic FRAs were also induced by several different types of chronic treatments in a region-specific manner in the brain. Thus, the chronic FRAs and associated chronic AP-1 complex could mediate some of the long-term changes in gene expression unique to the chronic-treated state as opposed to the acute-treated and normal states.

  3. A LIGHT-CURVE MODEL OF THE SYMBIOTIC NOVA PU Vul (1979): A VERY QUIET EXPLOSION WITH LONG-LASTING FLAT PEAK

    SciTech Connect

    Kato, Mariko; Hachisu, Izumi; Cassatella, Angelo; Gonzalez-Riestra, Rosario

    2011-02-01

    We present a light-curve model of the symbiotic nova PU Vul (Nova Vulpeculae 1979) that shows a long-lasting flat peak with no spectral indication of wind mass loss before decline. Our quasi-evolution models consisting of a series of static solutions explain both the optical flat peak and ultraviolet (UV) light curve simultaneously. The white dwarf mass is estimated to be {approx}0.6 M{sub sun}. We also provide a new determination of the reddening, E(B - V) = 0.43 {+-} 0.05, from UV spectral analysis. Theoretical light-curve fitting of UV 1455 A provides the distance of d = 3.8 {+-} 0.7 kpc.

  4. A long-lasting, single-dose nasal vaccine for Ebola: a practical armament for an outbreak with significant global impact.

    PubMed

    Jonsson-Schmunk, Kristina; Croyle, Maria A

    2015-05-01

    In response to the severity and scale of the 2014 Ebola outbreak, several experimental vaccines were granted fast-track status for clinical testing. Although they may provide long-lasting protection from Ebola, they are, in their current states, far from optimal for populations that need them the most. In this context, nasal immunization addresses the: immune response required at the mucosa where Ebola initiates infection; needs of a population in terms of cost and compliance; and potency of each platform as they contain viruses that naturally infect the respiratory tract. Understanding the attributes of nasal immunization and its application will lead to potent vaccines that can effectively end Ebola and other emerging infectious diseases in developing and industrialized countries.

  5. Long-lasting inhibitory effect of apple and orange juices, but not grapefruit juice, on OATP2B1-mediated drug absorption.

    PubMed

    Shirasaka, Yoshiyuki; Shichiri, Megumi; Murata, Yukiko; Mori, Takanori; Nakanishi, Takeo; Tamai, Ikumi

    2013-03-01

    Enzyme-based grapefruit juice (GFJ)-drug interactions are mainly due to mechanism-based irreversible inhibition of metabolizing enzyme CYP3A4 by GFJ components, but the transporter organic anion transporting polypeptide (OATP)2B1 is also a putative site of interaction between drugs and fruit juices (FJ) in the absorption process. Here we aimed to investigate the effect of preincubation with FJ on OATP2B1-mediated transport of drugs in vitro. When OATP2B1-expressing Xenopus oocytes were preincubated with GFJ, orange juice (OJ), or apple juice (AJ), AJ induced a remarkable decrease in OATP2B1-mediated estrone-3-sulfate uptake in a concentration-dependent manner (IC(50) = 1.5%). A similar but less potent effect was observed with OJ (IC(50) = 21%), whereas GFJ had no effect. Similar results were obtained in preincubation studies using fexofenadine. Preincubation with OJ and AJ resulted in time-dependent inhibition of OATP2B1. Again, AJ had the more potent effect; its action lasted for at least 240 minutes, suggesting that AJ irreversibly inhibits OATP2B1-mediated drug uptake. Kinetic analysis revealed that coincubation and preincubation with AJ reduced OATP2B1-mediated estrone-3-sulfate uptake via competitive and noncompetitive mechanisms, respectively. Thus, OATP2B1 is functionally impaired through both competitive and long-lasting inhibition mechanisms by AJ and OJ, but not GFJ. Interestingly, although GFJ but not AJ is able to irreversibly inhibit CYP3A4, in the case of OATP2B1, AJ but not GFJ has a long-lasting inhibitory effect. Accordingly, complex FJ-drug interactions may occur in vivo, and their clinical significance should be examined.

  6. Newcastle Disease Virus-Vectored Rabies Vaccine Is Safe, Highly Immunogenic, and Provides Long-Lasting Protection in Dogs and Cats ▿

    PubMed Central

    Ge, Jinying; Wang, Xijun; Tao, Lihong; Wen, Zhiyuan; Feng, Na; Yang, Songtao; Xia, Xianzhu; Yang, Chinglai; Chen, Hualan; Bu, Zhigao

    2011-01-01

    Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 109.8 50% egg infective doses (EID50)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 108.3 EID50 completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies. PMID:21632762

  7. Ionic composition of submicron particles (PM1.0) during the long-lasting haze period in January 2013 in Wuhan, central China.

    PubMed

    Cheng, Hairong; Gong, Wei; Wang, Zuwu; Zhang, Fan; Wang, Xinming; Lv, Xiaopu; Liu, Jia; Fu, Xiaoxin; Zhang, Gan

    2014-04-01

    In January 2013, a long-lasting severe haze episode occurred in Northern and Central China; at its maximum, it covered a land area of approximately 1.4 million km(2). In Wuhan, the largest city in Central China, this event was the most severe haze episode in the 21st century. Aerosol samples of submicron particles (PM1.0) were collected during the long-lasting haze episode at an urban site and a suburban site in Wuhan to investigate the ion characteristics of PM1.0 in this area. The mass concentrations of PM1.0 and its water-soluble inorganic ions (WSIIs) were almost at the same levels at two sites, which indicates that PM1.0 pollution occurs on a regional scale in Wuhan. WSIIs (Na(+), NH4(+), K(+), Mg(2+), Ca(2+), Cl(-), NO3(-) and SO4(2-)) were the dominant chemical species and constituted up to 48.4% and 47.4% of PM1.0 at WD and TH, respectively. The concentrations of PM1.0 and WSIIs on haze days were approximately two times higher than on normal days. The ion balance calculations indicate that the particles were more acidic on haze days than on normal days. The results of the back trajectory analysis imply that the high concentrations of PM1.0 and its water-soluble inorganic ions may be caused by stagnant weather conditions in Wuhan. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  8. Long-Lasting Attenuation of Amygdala-Kindled Seizures after Convection-Enhanced Delivery of Botulinum Neurotoxins A and B into the Amygdala in Rats

    PubMed Central

    Gasior, Maciej; Tang, Rebecca

    2013-01-01

    Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula–stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convection-enhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64-day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally, maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region. PMID:23772062

  9. Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

    PubMed

    Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; Hass, Ulla

    2008-10-01

    Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity.

  10. Long-lasting effects of fluoxetine and/or exercise augmentation on bio-behavioural markers of depression in pre-pubertal stress sensitive rats.

    PubMed

    Schoeman, Jacobus C; Steyn, Stephanus F; Harvey, Brian H; Brink, Christiaan B

    2017-04-14

    Juvenile depression is of great concern with only limited treatment currently approved. Delayed onset of action, low remission and high relapse rates, and potential long-lasting consequences further complicates treatment and highlights the need for new treatment options. Studies reporting on long-lasting effects of early-life treatment have reported conflicting results, with the pre-adolescent period mostly overlooked. The anti-depressive effect of exercise, as a possible treatment option or augmentation strategy, is dependent on age and exercise intensity. We investigated the immediate (i.e. postnatal day 35 (PND35)) and lasting (PND60 to PND61) effects of pre-pubertal (PND21 to PND34) fluoxetine and/or exercise on bio-behavioural markers of depression and oxidative stress in stress sensitive Flinders Sensitive Line rats. Low, but not moderate, intensity exercise or 5, but not 10, mg/kg/day fluoxetine displayed anti-depressant-like properties at PND35. Pre-pubertal treatment with 5mg/kg/day fluoxetine or low intensity exercise exerted lasting anti-depressive-like effects into adulthood, whereas the combination of these two treatments did not. Furthermore, the combination of fluoxetine plus exercise reduced hippocampal BDNF levels as compared to exercise alone, which may explain the latter findings. In all treatment groups hippocampal SOD activity was significantly increased at PND61, suggesting an increased anti-oxidant capacity in adulthood. In conclusion, the data confirm the anti-depressant-like properties of both early-life fluoxetine and exercise in a genetic animal model of depression. However, optimal lasting effects of early-life interventions may require adjustment of antidepressant dose and/or exercise intensity to developmental age, and that a combination of antidepressant and exercise may not necessarily be augmentative. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Method development for the determination of arsenic by sequential injection/anodic stripping voltammetry using long-lasting gold-modified screen-printed carbon electrode.

    PubMed

    Punrat, Eakkasit; Chuanuwatanakul, Suchada; Kaneta, Takashi; Motomizu, Shoji; Chailapakul, Orawon

    2013-11-15

    An automated method has been developed for determining the concentration of inorganic arsenic. The technique uses sequential injection/anodic stripping voltammetry with a long-lasting gold-modified screen-printed carbon electrode. The long-lasting gold electrode was electrochemically deposited onto a screen-printed carbon electrode at a potential of -0.5 V vs. Ag/AgCl in a supporting electrolyte solution of 1M hydrochloric acid. Under optimal conditions and the applied potentials, the electrode demonstrated that it can be used for a long time without a renewal process. The linear range for the determination of arsenic(III) was 1-100 μg L(-1), and the limit of detection (LOD) in standard solutions was as low as 0.03 μg L(-1) for a deposition time of 120 s and sample volume of 1 mL. This method was used to determine the concentration of arsenic(III) in water samples with satisfactory results. The LOD in real samples was found to be 0.5 μg L(-1). In addition, speciation between arsenic(III) and arsenic(V) has been achieved with the proposed method using deposition potentials of -0.5 V and -1.5 V for the determination of the arsenic(III) concentration and the total arsenic concentration, respectively; the results were acceptable. The proposed method is an automated system that offers a less expensive alternative for determining trace amounts of inorganic arsenic. © 2013 Elsevier B.V. All rights reserved.

  12. Identification of a long-lasting form of odor adaptation that depends on the carbon Monoxide/cGMP second-messenger system.

    PubMed

    Zufall, F; Leinders-Zufall, T

    1997-04-15

    The diffusible messenger carbon monoxide (CO) has been proposed to mediate endogenous cyclic guanosine 3',5'-monophosphate (cGMP) formation and sensory adaptation in vertebrate olfactory receptor neurons (ORNs). We have identified and characterized a long-lasting form of odor response adaptation (LLA) that operates at the level of isolated salamander ORNs and does not require any interactions from other cells. Manifestations of LLA are seen in reduced amplitude and prolonged kinetics of the cAMP-mediated excitatory odor response and the generation of a persistent current component that lasts for several minutes and is attributable to cyclic nucleotide-gated (CNG) channel activation by cGMP. Because these effects can be mimicked by micromolar amounts of exogenous cGMP or CO, we applied various inhibitors of cGMP formation. LLA is abolished selectively by heme oxygenase inhibitors known to prevent CO release and cGMP formation in ORNs, whereas odor excitation remains unaffected. In contrast, blockers of nitric oxide synthase are unable to eliminate LLA. Several controls rule out a contribution of nonspecific actions to the effects of CO inhibitors. The results indicate that endogenous CO/cGMP signals contribute to olfactory adaptation and underlie the control of gain and sensitivity of odor transduction. The findings offer a mechanism by which a single, brief odor stimulus can be translated into long-lasting intracellular changes that could play an important role in the perceptual adaptation to odors, and explain the longstanding puzzle that the olfactory CNG channels can be gated by both cAMP and cGMP.

  13. Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

    PubMed Central

    Cupertino, Marli C; Costa, Kyvia L C; Santos, Daiane C M; Novaes, Rômulo D; Condessa, Suellen S; Neves, Ana C; Oliveira, Juraci A; Matta, Sérgio L P

    2013-01-01

    Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis. PMID:24020407

  14. A qualitative study on the acceptability and preference of three types of long-lasting insecticide-treated bed nets in Solomon Islands: implications for malaria elimination.

    PubMed

    Atkinson, Jo-An; Bobogare, Albino; Fitzgerald, Lisa; Boaz, Leonard; Appleyard, Bridget; Toaliu, Hilson; Vallely, Andrew

    2009-06-04

    In March 2008, the Solomon Islands and Vanuatu governments raised the goal of their National Malaria Programmes from control to elimination. Vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal bed nets (LLINs) are key integral components of this programme. Compliance with these interventions is dependent on their acceptability and on the socio-cultural context of the local population. These factors need to be investigated locally prior to programme implementation. Twelve focus group discussions (FGDs) were carried out in Malaita and Temotu Provinces, Solomon Islands in 2008. These discussions explored user perceptions of acceptability and preference for three brands of long-lasting insecticide-treated bed nets (LLINs) and identified a number of barriers to their proper and consistent use. Mosquito nuisance and perceived threat of malaria were the main determinants of bed net use. Knowledge of malaria and the means to prevent it were not sufficient to guarantee compliance with LLIN use. Factors such as climate, work and evening social activities impact on the use of bed nets, particularly in men. LLIN acceptability plays a varying role in compliance with their use in villages involved in this study. Participants in areas of reported high and year round mosquito nuisance and perceived threat of malaria reported LLIN use regardless of any reported unfavourable characteristics. Those in areas of low or seasonal mosquito nuisance were more likely to describe the unfavourable characteristics of LLINs as reasons for their intermittent or non-compliance. The main criterion for LLIN brand acceptability was effectiveness in preventing mosquito bites and malaria. Discussions highlighted considerable confusion around LLIN care and washing which may be impacting on their effectiveness and reducing their acceptability in Solomon Islands. Providing LLINs that are acceptable will be more important for improving compliance in areas of low

  15. Plastic Surgery

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Plastic Surgery KidsHealth / For Teens / Plastic Surgery What's in ... her forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word " ...

  16. The alphabet of intrinsic disorder

    PubMed Central

    Uversky, Vladimir N

    2013-01-01

    The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their “disorder promoting potencies,” which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue. PMID:28516010

  17. Left-sided hemiparesis, pain frequency, and decreased passive shoulder range of abduction are predictors of long-lasting poststroke shoulder pain.

    PubMed

    Lindgren, Ingrid; Lexell, Jan; Jönsson, Ann-Cathrin; Brogårdh, Christina

    2012-08-01

    To determine the proportion of persons with poststroke shoulder pain 4 months after onset of the stroke in whom long-lasting shoulder pain develops and to assess the extent to which age, side of paresis at stroke onset, pain frequency and pain intensity, passive shoulder range of motion, resistance to passive movements, motor function, and subluxation at 4 months after stroke predict shoulder pain 1 year later. A prospective study. A university hospital outpatient clinical setting. Fifty-eight men and women with their first-ever stroke (mean age, 71 years) and affected sensory-motor function in the upper extremity at stroke onset who all reported shoulder pain in the affected side 4 months after onset of the stroke. At 4 and 16 months after having a stroke, the participants rated their self-perceived shoulder pain (frequency and intensity). Passive range of shoulder abduction and external rotation, resistance to passive movements in the elbow, and motor function in the shoulder were assessed by a physical therapist. A question about pain frequency (constant, often, or occasional), the Visual Analogue Scale for Pain for self-perceived shoulder pain intensity, a goniometer for range of motion, the Modified Ashworth Scale for resistance to passive movements, and the Motor Assessment Scale for motor function. Of the 58 participants who had shoulder pain 4 months after having a stroke, 42 (72%) still had pain at 16 months. The logistic regression indicated an association between shoulder pain at 16 months and left-sided hemiparesis at stroke onset (P = .01; odds ratio [OR] 10.47; 95% confidence interval [CI] 1.92-57.05), pain frequency (P = .02; OR 6.85; 95% CI 1.46-32.14), decreased passive abduction at 4 months (P = .05; OR 4.46; 95% CI 0.99-20.10), and age (P = .07; OR 1.05; 95% CI 1.0-1.12). A high proportion of persons with shoulder pain 4 months after having a stroke are at risk of having persistent shoulder pain 1 year later. Left-sided hemiparesis, pain reported

  18. Malaria in Dielmo, a Senegal village: Is its elimination possible after seven years of implementation of long-lasting insecticide-treated nets?

    PubMed

    Wotodjo, Amélé Nyedzie; Doucoure, Souleymane; Gaudart, Jean; Diagne, Nafissatou; Diene Sarr, Fatoumata; Faye, Ngor; Tall, Adama; Raoult, Didier; Sokhna, Cheikh

    2017-01-01

    The malaria burden has decreased significantly in recent years in Africa through the widespread use of artemisinin-based combination therapy (ACT) and long-lasting insecticide-treated nets (LLINs). However, the occurrence of malaria resurgences, the loss of immunity of exposed populations constitute among other factors, serious concerns about the future of malaria elimination efforts. This study investigated the evolution of malaria morbidity in Dielmo (Senegal) before and after the implementation of LLINs. A longitudinal study was carried out in Dielmo over eight years, from July 2007 to July 2015. In July 2008, LLINs were offered to all villagers, and in July 2011 and August 2014 the LLINs were renewed. A survey on LLINs use was done each quarter of the year. Thick smears stained with Giemsa, a rapid diagnostic test (RDT) and quantitative polymerase chain reaction (PCR) methods were performed for all cases of fever to assess malaria clinical attacks. Malaria cases were treated with ACT since June 2006. Malaria morbidity has decreased significantly since the implementation of LLINs in Dielmo, together with ACT. However, malaria resurgences have occurred twice during the seven years of LLINs use. These resurgences occurred the first time during the third year after the introduction of LLINs (aIRR (adjusted incidence-rate ratio) [95%CI] = 5.90 [3.53; 9.88] p< 0.001) and a second time during the third year after the renewal of LLINs (aIRR [95%CI] = 5.60 [3.34; 9.39] p< 0.001). Sixty-nine percent (69%) of the nets tested for their long-lasting insecticidal activity remained effective after 3 years of use. Good management of malaria cases by the use of ACT as first-line treatment against malaria in addition to the use of LLINs has significantly reduced malaria in Dielmo and allowed to reach the phase of pre-elimination of the disease. However, the occurrence of malaria resurgences raised serious concerns about malaria elimination, which would require additional tools

  19. Synthetic Sex Pheromone in a Long-Lasting Lure Attracts the Visceral Leishmaniasis Vector, Lutzomyia longipalpis, for up to 12 Weeks in Brazil

    PubMed Central

    Bray, Daniel P.; Carter, Vicky; Alves, Graziella B.; Brazil, Reginaldo P.; Bandi, Krishna K.; Hamilton, James G. C.

    2014-01-01

    Current control methodologies have not prevented the spread of visceral leishmaniasis (VL) across Brazil. Here, we describe the development of a new tool for controlling the sand fly vector of the disease: a long-lasting lure, which releases a synthetic male sex pheromone, attractive to both sexes of Lutzomyia longipalpis. This device could be used to improve the effectiveness of residual insecticide spraying as a means of sand fly control, attracting L. longipalpis to insecticide-treated animal houses, where they could be killed in potentially large numbers over a number of weeks. Different lure designs releasing the synthetic pheromone (±)-9-methylgermacrene-B (CAS 183158-38-5) were field-tested in Araçatuba, São Paulo (SP). Experiments compared numbers of sand flies caught overnight in experimental chicken sheds with pheromone lures, to numbers caught in control sheds without pheromone. Prototype lures, designed to last one night, were first used to confirm the attractiveness of the pheromone in SP, and shown to attract significantly more flies to test sheds than controls. Longer-lasting lures were tested when new, and at fortnightly intervals. Lures loaded with 1 mg of pheromone did not attract sand flies for more than two weeks. However, lures loaded with 10 mg of pheromone, with a releasing surface of 15 cm2 or 7.5 cm2, attracted female L. longipalpis for up to ten weeks, and males for up to twelve weeks. Approximately five times more sand flies were caught with 7.5 cm2 10 mg lures when first used than occurred naturally in non-experimental chicken resting sites. These results demonstrate that these lures are suitably long-lasting and attractive for use in sand fly control programmes in SP. To our knowledge, this is the first sex pheromone-based technology targeting an insect vector of a neglected human disease. Further studies should explore the general applicability of this approach for combating other insect-borne diseases. PMID:24651528

  20. Synthetic sex pheromone in a long-lasting lure attracts the visceral leishmaniasis vector, Lutzomyia longipalpis, for up to 12 weeks in Brazil.

    PubMed

    Bray, Daniel P; Carter, Vicky; Alves, Graziella B; Brazil, Reginaldo P; Bandi, Krishna K; Hamilton, James G C

    2014-03-01

    Current control methodologies have not prevented the spread of visceral leishmaniasis (VL) across Brazil. Here, we describe the development of a new tool for controlling the sand fly vector of the disease: a long-lasting lure, which releases a synthetic male sex pheromone, attractive to both sexes of Lutzomyia longipalpis. This device could be used to improve the effectiveness of residual insecticide spraying as a means of sand fly control, attracting L. longipalpis to insecticide-treated animal houses, where they could be killed in potentially large numbers over a number of weeks. Different lure designs releasing the synthetic pheromone (±)-9-methylgermacrene-B (CAS 183158-38-5) were field-tested in Araçatuba, São Paulo (SP). Experiments compared numbers of sand flies caught overnight in experimental chicken sheds with pheromone lures, to numbers caught in control sheds without pheromone. Prototype lures, designed to last one night, were first used to confirm the attractiveness of the pheromone in SP, and shown to attract significantly more flies to test sheds than controls. Longer-lasting lures were tested when new, and at fortnightly intervals. Lures loaded with 1 mg of pheromone did not attract sand flies for more than two weeks. However, lures loaded with 10 mg of pheromone, with a releasing surface of 15 cm2 or 7.5 cm2, attracted female L. longipalpis for up to ten weeks, and males for up to twelve weeks. Approximately five times more sand flies were caught with 7.5 cm2 10 mg lures when first used than occurred naturally in non-experimental chicken resting sites. These results demonstrate that these lures are suitably long-lasting and attractive for use in sand fly control programmes in SP. To our knowledge, this is the first sex pheromone-based technology targeting an insect vector of a neglected human disease. Further studies should explore the general applicability of this approach for combating other insect-borne diseases.

  1. Over-the-scope-clip closure of long lasting gastrocutaneous fistula after percutaneous endoscopic gastrostomy tube removal in immunocompromised patients: A single center case series.

    PubMed

    Heinrich, Henriette; Gubler, Christoph; Valli, Piero V

    2017-02-16

    Over-the-scope-clips (OTSC®) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC® treatment have grown in number and also include gastro cutaneous fistula (GCF) after percutaneous endoscopic gastrostomy (PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC® closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC® closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism (cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5 (21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d (range 144-850 d). The intervention was well tolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC® closure of long lasting GCF in five consecutive middle-aged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC® was achieved in all patients

  2. Long-lasting ameliorating effects of the oligodeoxynucleotide IMT504 on mechanical allodynia and hindpaw edema in rats with chronic hindpaw inflammation.

    PubMed

    Leiguarda, Candelaria; Coronel, María Florencia; Montaner, Alejandro Daniel; Villar, Marcelo José; Brumovsky, Pablo Rodolfo

    2018-02-14

    Previously we showed that systemic administration of IMT504 prevents or ameliorates mechanical and thermal allodynia in rats with sciatic nerve crush. Here we analyzed if IMT504 is also effective in reducing mechanical allodynia and inflammation in rats undergoing hindpaw inflammation. Male Sprague-Dawley rats received unilateral intraplantar injection of complete Freund́s adjuvant (CFA), and were grouped into: 1) untreated CFA, 2) vehicle-treated CFA, 3) IMT504-treated CFA (5 daily (5*) doses of 20, 2 or 0.2 mg/kg, or 3*2 mg/kg). Naïve groups were also included. Finally, early (immediately after intraplantar CFA) and late (7 days after intraplantar CFA) IMT504 treatment protocols were also tested. Hindpaw mechanical allodynia, dorsoventral thickness, edema and cellular infiltration of ipsilateral hindpaws were evaluated in all groups. Untreated CFA rats exhibited mechanical allodynia of quick onset (day 1) and long duration (7 weeks inclusive). Early and late treatments with 5*20 mg/kg IMT504 to CFA rats resulted in both quick and long-lasting antiallodynic effects, as compared to untreated CFA rats. This was also the case in CFA rats undergoing late IMT504 treatment at lower doses (3* and 5*2 mg/kg). Very low doses of IMT504 (5*0.2 mg/kg) only showed a mild improvement in withdrawal threshold, never reaching basal levels. Finally, rats treated with 3* or 5*2 mg/kg or 5*0.2 mg/kg exhibited significant decreases in dorsoventral thickness, edema, and inflammatory cell infiltration of the inflamed hindpaw. Early and late administration of IMT504 results in quick and long-lasting reductions in mechanical allodynia and hindpaw edema. While the mechanisms behind these effects remain to be established, data suggests that IMT504 administration could be a promising strategy in the control of inflammatory pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. An experimental hut evaluation of Olyset Plus, a long-lasting insecticidal net treated with a mixture of permethrin and piperonyl butoxide, against Anopheles fluviatilis in Odisha State, India.

    PubMed

    Gunasekaran, Kasinathan; Sahu, Sudhansu Sekhar; Vijayakumar, Tharmalingam; Subramanian, Swaminathan; Yadav, Rajpal Singh; Pigeon, Olivier; Jambulingam, Purushothaman

    2016-07-21

     WHO efficacy criteria of Phase II evaluation for LLIN. However, the benefit of incorporating PBO and permethrin together in a long-lasting treatment could not be demonstrated in the current study as the target vector species was fully susceptible to pyrethroids. Olyset Plus, with its intrinsic bio-efficacy could be an effective vector control tool to prevent transmission of malaria by susceptible vectors like An. fluviatilis. However, the results of the current study need to be further supported by testing the net at village level (Phase III) for community acceptability. Before taking the net to village level, it needs to be verified whether the net is better than pyrethroid nets in terms of bio-efficacy against resistant An. culicifacies, another malaria vector that has developed resistance to synthetic pyrethroids in India.

  4. Application of a long-lasting colloidal substrate with pH and hydrogen sulfide control capabilities to remediate TCE-contaminated groundwater.

    PubMed

    Sheu, Y T; Chen, S C; Chien, C C; Chen, C C; Kao, C M

    2015-03-02

    A long-lasting emulsified colloidal substrate (LECS) was developed for continuous carbon and nanoscale zero-valent iron (nZVI) release to remediate trichloroethylene (TCE)-contaminated groundwater under reductive dechlorinating conditions. The developed LECS contained nZVI, vegetable oil, surfactants (Simple Green™ and lecithin), molasses, lactate, and minerals. An emulsification study was performed to evaluate the globule droplet size and stability of LECS. The results show that a stable oil-in-water emulsion with uniformly small droplets (0.7 μm) was produced, which could continuously release the primary substrates. The emulsified solution could serve as the dispensing agent, and nZVI particles (with diameter 100-200 nm) were distributed in the emulsion evenly without aggregation. Microcosm results showed that the LECS caused a rapid increase in the total organic carbon concentration (up to 488 mg/L), and reductive dechlorination of TCE was significantly enhanced. Up to 99% of TCE (with initial concentration of 7.4 mg/L) was removed after 130 days of operation. Acidification was prevented by the production of hydroxide ion by the oxidation of nZVI. The formation of iron sulfide reduced the odor from produced hydrogen sulfide. Microbial analyses reveal that dechlorinating bacteria existed in soils, which might contribute to TCE dechlorination. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Does long-lasting sports practice increase the risk of atrial fibrillation in healthy middle-aged men? Weak suggestions, no objective evidence.

    PubMed

    Delise, Pietro; Sitta, Nadir; Berton, Giuseppe

    2012-06-01

    Some authors have suggested that sports activity can increase the risk of atrial fibrillation in healthy middle-aged men. Therefore, sport activity, although it prevents coronary artery disease, might be the cause of a potentially dangerous arrhythmia. To verify this assumption, we critically analyzed the current literature including original articles, reviews and meta-analyses. All published articles showed several limitations. The data provided by published studies support the following conclusions: the incidence of atrial fibrillation in sporting middle-aged men is rare (<0.5% per year); a possible facilitating effect on atrial fibrillation is limited to vigorous endurance exercise, not to less vigorous sports; there are no convincing data to demonstrate that sport itself may be the cause of atrial fibrillation in healthy middle-aged men; and a facilitating effect of long-lasting sport cannot be excluded in middle-aged individuals with cardiovascular disorders. Nevertheless, the beneficial effects of exercise should offset this supposed risk, which, albeit increased, remains low.

  6. Long-lasting insecticide-treated house screens and targeted treatment of productive breeding-sites for dengue vector control in Acapulco, Mexico

    PubMed Central

    Che-Mendoza, Azael; Guillermo-May, Guillermo; Herrera-Bojórquez, Josué; Barrera-Pérez, Mario; Dzul-Manzanilla, Felipe; Gutierrez-Castro, Cipriano; Arredondo-Jiménez, Juan I.; Sánchez-Tejeda, Gustavo; Vazquez-Prokopec, Gonzalo; Ranson, Hilary; Lenhart, Audrey; Sommerfeld, Johannes; McCall, Philip J.; Kroeger, Axel; Manrique-Saide, Pablo

    2015-01-01

    Background Long-lasting insecticidal net screens (LLIS) fitted to domestic windows and doors in combination with targeted treatment (TT) of the most productive Aedes aegypti breeding sites were evaluated for their impact on dengue vector indices in a cluster-randomised trial in Mexico between 2011 and 2013. Methods Sequentially over 2 years, LLIS and TT were deployed in 10 treatment clusters (100 houses/cluster) and followed up over 24 months. Cross-sectional surveys quantified infestations of adult mosquitoes, immature stages at baseline (pre-intervention) and in four post-intervention samples at 6-monthly intervals. Identical surveys were carried out in 10 control clusters that received no treatment. Results LLIS clusters had significantly lower infestations compared to control clusters at 5 and 12 months after installation, as measured by adult (male and female) and pupal-based vector indices. After addition of TT to the intervention houses in intervention clusters, indices remained significantly lower in the treated clusters until 18 (immature and adult stage indices) and 24 months (adult indices only) post-intervention. Conclusions These safe, simple affordable vector control tools were well-accepted by study participants and are potentially suitable in many regions at risk from dengue worldwide. PMID:25604761

  7. Physical Durability of Two Types of Long-Lasting Insecticidal Nets (LLINs) Three Years after a Mass LLIN Distribution Campaign in Mozambique, 2008–2011

    PubMed Central

    Morgan, Juliette; Abílio, Ana Paula; do Rosario Pondja, Maria; Marrenjo, Dulcisária; Luciano, Jacinta; Fernandes, Guilhermina; Sabindy, Samira; Wolkon, Adam; Ponce de Leon, Gabriel; Chan, Adeline; Eng, Jodi Vanden

    2015-01-01

    We conducted a prospective evaluation to measure the physical durability of two brands of long-lasting insecticidal nets (LLINs) distributed during a campaign in 2008 in Nampula Province, Mozambique. Households with LLINs tagged during the campaign (6,000) were geo-located (34%) and a random sample was selected for each of 3 years of follow-up. The LLINs were evaluated in the field and a laboratory for presence of holes and a proportional hole index (pHI) was calculated following the World Health Organization guidelines. We performed 567 interviews (79.0%) and found 75.3% (72.1–78.4%) of households retained at least one LLIN after 3 years; the most common cause of attrition was damage beyond repair (51.0%). Hole damage was evident after 1 year, and increased by year. Olyset had a significantly greater mean number of holes and pHI compared with PermaNet 2.0 brand (all P values ≤ 0.001). Additional information about LLIN durability is recommended to improve malaria control efforts. PMID:25404079

  8. Long-lasting changes in brain activation induced by a single REAC technology pulse in Wi-Fi bands. Randomized double-blind fMRI qualitative study.

    PubMed

    Rinaldi, Salvatore; Mura, Marco; Castagna, Alessandro; Fontani, Vania

    2014-07-11

    The aim of this randomized double-blind study was to evaluate in healthy adult subjects, with functional magnetic resonance imaging (fMRI), long lasting changes in brain activation patterns following administration of a single, 250 milliseconds pulse emitted with radio-electric asymmetric conveyer (REAC) technology in the Wi-Fi bands. The REAC impulse was not administered during the scan, but after this, according to a protocol that has previously been demonstrated to be effective in improving motor control and postural balance, in healthy subjects and patients. The study was conducted on 33 healthy volunteers, performed with a 1.5 T unit while operating a motor block task involving cyclical and alternating flexion and extension of one leg. Subsequently subjects were randomly divided into a treatment and a sham treatment control group. Repeated fMRI examinations were performed following the administration of the REAC pulse or sham treatment. The Treated group showed cerebellar and ponto-mesencephalic activation components that disappeared in the second scan, while these activation components persisted in the Sham group. This study shows that a very weak signal, such as 250 milliseconds Wi-Fi pulse, administered with REAC technology, could lead to lasting effects on brain activity modification.

  9. Long-lasting changes in brain activation induced by a single REAC technology pulse in Wi-Fi bands. Randomized double-blind fMRI qualitative study

    PubMed Central

    Rinaldi, Salvatore; Mura, Marco; Castagna, Alessandro; Fontani, Vania

    2014-01-01

    The aim of this randomized double-blind study was to evaluate in healthy adult subjects, with functional magnetic resonance imaging (fMRI), long lasting changes in brain activation patterns following administration of a single, 250 milliseconds pulse emitted with radio-electric asymmetric conveyer (REAC) technology in the Wi-Fi bands. The REAC impulse was not administered during the scan, but after this, according to a protocol that has previously been demonstrated to be effective in improving motor control and postural balance, in healthy subjects and patients. The study was conducted on 33 healthy volunteers, performed with a 1.5 T unit while operating a motor block task involving cyclical and alternating flexion and extension of one leg. Subsequently subjects were randomly divided into a treatment and a sham treatment control group. Repeated fMRI examinations were performed following the administration of the REAC pulse or sham treatment. The Treated group showed cerebellar and ponto-mesencephalic activation components that disappeared in the second scan, while these activation components persisted in the Sham group. This study shows that a very weak signal, such as 250 milliseconds Wi-Fi pulse, administered with REAC technology, could lead to lasting effects on brain activity modification. PMID:25011544

  10. History of Illicit Stimulant Use Is Not Associated with Long-Lasting Changes in Learning of Fine Motor Skills in Humans

    PubMed Central

    Todd, Gabrielle; Pearson-Dennett, Verity; Flavel, Stanley C.; Haberfield, Miranda; Edwards, Hannah; White, Jason M.

    2016-01-01

    Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent individuals with a history of primarily methamphetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users (n = 21; 27 ± 6 yrs) and two gender-matched control groups comprising nondrug users (n = 16; 22 ± 4 yrs) and cannabis users (n = 16; 23 ± 5 yrs). Motor learning was assessed with a three-minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in individuals with a history of illicit stimulant use. PMID:26819778

  11. History of Illicit Stimulant Use Is Not Associated with Long-Lasting Changes in Learning of Fine Motor Skills in Humans.

    PubMed

    Todd, Gabrielle; Pearson-Dennett, Verity; Flavel, Stanley C; Haberfield, Miranda; Edwards, Hannah; White, Jason M

    2016-01-01

    Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent individuals with a history of primarily methamphetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users (n = 21; 27 ± 6 yrs) and two gender-matched control groups comprising nondrug users (n = 16; 22 ± 4 yrs) and cannabis users (n = 16; 23 ± 5 yrs). Motor learning was assessed with a three-minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in individuals with a history of illicit stimulant use.

  12. Scale-up of a programme for malaria vector control using long-lasting insecticide-treated nets: lessons from South Sudan.

    PubMed

    Chanda, Emmanuel; Remijo, Constantino D; Pasquale, Harriet; Baba, Samson P; Lako, Richard L

    2014-04-01

    Long-lasting insecticidal nets (LLINs) are important tools in malaria control. South Sudan, like many other endemic countries, has struggled to improve LLIN coverage and utilization. In 2006, Southern Sudan - known as South Sudan after independence in 2011 - initiated a strategic plan to increase LLIN coverage so that at least 60% of households had at least one LLIN each. By 2008, the target coverage was 80% of households and the Global Fund had financed a phased scale-up of LLIN distribution in the region. South Sudan's entire population is considered to be at risk of malaria. Poor control of the vectors and the large-scale movements of returnees, internally displaced people and refugees have exacerbated the problem. By 2012, approximately 8.0 million LLINs had been distributed in South Sudan. Between 2006 and 2009, the percentage of households possessing at least one LLIN increased from about 12% to 53% and LLIN utilization rates increased from 5 to 25% among children younger than 5 years and from 5 to 36% among pregnant women. The number of recorded malaria cases increased from 71 948 in 2008 to 1 198 357 in 2012. In post-conflict settings, a phased programme for the national scale-up of LLIN coverage may not have a substantial impact. A nationwide campaign that is centrally coordinated and based on sound guidelines may offer greater benefits. A strong partnership base and effective channels for the timely and supplementary deployment of LLINs may be essential for universal coverage.

  13. Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity

    NASA Astrophysics Data System (ADS)

    Dranoff, Glenn; Jaffee, Elizabeth; Lazenby, Audrey; Golumbek, Paul; Levitsky, Hyam; Brose, Katja; Jackson, Valerie; Hamada, Hirofumi; Pardoll, Drew; Mulligan, Richard C.

    1993-04-01

    To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4^+ and CD8^+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

  14. Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses

    PubMed Central

    Mohan, Teena; Berman, Zachary; Luo, Yuan; Wang, Chao; Wang, Shelly; Compans, Richard W.; Wang, Bao-Zhong

    2017-01-01

    Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups. PMID:28067290

  15. Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses.

    PubMed

    Mohan, Teena; Berman, Zachary; Luo, Yuan; Wang, Chao; Wang, Shelly; Compans, Richard W; Wang, Bao-Zhong

    2017-01-09

    Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups.

  16. Crotoxin is responsible for the long-lasting anti-inflammatory effect of Crotalus durissus terrificus snake venom: involvement of formyl peptide receptors.

    PubMed

    Nunes, F P B; Zychar, B C; Della-Casa, M S; Sampaio, S C; Gonçalves, L R C; Cirillo, M C

    2010-06-01

    In the present study, it was investigated which components are responsible for the anti-inflammatory properties of Crotalus durissus terrificus venom (CdtV). The effect of crotoxin, as well as of other CdtV components was evaluated on edema, cell migration and alterations in leukocyte-endothelium interactions induced by carrageenan. Crotoxin (40 microg kg(-1)) was injected at different time periods before or after the injection of carrageenan (15 mg kg(-1)) into the mouse hind paw, peritoneum or scrotum. Results showed that crotoxin, but not other CdtV components, significantly inhibited inflammatory edema and cell migration when administered before or after carrageenan injection in mice. This toxin also prevented the occurrence of alterations in leukocyte-endothelium interactions induced by carrageenan injection, such as the increase in adhered cells. In animals pretreated with Boc2 (a selective antagonist of formyl peptide receptors), crotoxin showed neither inhibitory effects on edema and cell migration, nor prevented alterations in leukocyte-endothelium interactions induced by carrageenan. These findings demonstrate that crotoxin is the component responsible for the long-lasting anti-inflammatory activity of crude C. durissus terrificus venom, and activation of formyl peptide receptors seems to play a major role in this effect. Copyright 2009 Elsevier Ltd. All rights reserved.

  17. Seizures in the developing brain result in a long-lasting decrease in GABA(B) inhibitory postsynaptic currents in the rat hippocampus.

    PubMed

    Qu, Lintao; Boyce, Richard; Leung, L Stan

    2010-03-01

    Whether seizures in the developing brain cause long-term changes in the mature brain has been debated. We tested the hypothesis that a model of early-life seizures, induced by systemic injection of a GABA(B) receptor antagonist CGP56999A in immature rats, decreased GABA(B) receptor-mediated inhibitory postsynaptic currents (IPSCs) in the hippocampus of adolescent rats. Whole-cell recordings were made in CA1 pyramidal cells and dentate gyrus (DG) granule cells in vitro, 30-45 days after the rats had seizures induced by CGP56999A (1-1.5 mg/kg i.p.) or control saline injection on postnatal day 15. GABA(B) receptor-mediated IPSCs were reduced in DG neurons but not in CA1 neurons of early-life seizure rats as compared to controls. Additionally, hippocampal neurons of early-life seizure rats, as compared to those in control rats, showed a more depolarized resting membrane potential in both CA1 and DG, and a larger input resistance but reduced spike frequency adaptation in DG neurons. In conclusion, early-life seizures result in a long-lasting reduction in GABA(B) receptor-mediated transmission in DG principal neurons and depolarization in CA1 and DG principal neurons. These alterations are expected to increase seizure susceptibility in the adult brain. 2009 Elsevier Inc. All rights reserved.

  18. Effectiveness and feasibility of long-lasting insecticide-treated curtains and water container covers for dengue vector control in Colombia: a cluster randomised trial.

    PubMed

    Quintero, Juliana; García-Betancourt, Tatiana; Cortés, Sebastian; García, Diana; Alcalá, Lucas; González-Uribe, Catalina; Brochero, Helena; Carrasquilla, Gabriel

    2015-02-01

    Long-lasting insecticide-treated net (LLIN) window and door curtains alone or in combination with LLIN water container covers were analysed regarding effectiveness in reducing dengue vector density, and feasibility of the intervention. A cluster randomised trial was conducted in an urban area of Colombia comparing 10 randomly selected control and 10 intervention clusters. In control clusters, routine vector control activities were performed. The intervention delivered first, LLIN curtains (from July to August 2013) and secondly, water container covers (from October to March 2014). Cross-sectional entomological surveys were carried out at baseline (February 2013 to June 2013), 9 weeks after the first intervention (August to October 2013), and 4-6 weeks after the second intervention (March to April 2014). Curtains were installed in 922 households and water container covers in 303 households. The Breteau index (BI) fell from 14 to 6 in the intervention group and from 8 to 5 in the control group. The additional intervention with LLIN covers for water containers showed a significant reduction in pupae per person index (PPI) (p=0.01). In the intervention group, the PPI index showed a clear decline of 71% compared with 25% in the control group. Costs were high but options for cost savings were identified. Short term impact evaluation indicates that the intervention package can reduce dengue vector density but sustained effect will depend on multiple factors. © The author 2015. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.

  19. Effectiveness and feasibility of long-lasting insecticide-treated curtains and water container covers for dengue vector control in Colombia: a cluster randomised trial

    PubMed Central

    Quintero, Juliana; García-Betancourt, Tatiana; Cortés, Sebastian; García, Diana; Alcalá, Lucas; González-Uribe, Catalina; Brochero, Helena; Carrasquilla, Gabriel

    2015-01-01

    Background Long-lasting insecticide-treated net (LLIN) window and door curtains alone or in combination with LLIN water container covers were analysed regarding effectiveness in reducing dengue vector density, and feasibility of the intervention. Methods A cluster randomised trial was conducted in an urban area of Colombia comparing 10 randomly selected control and 10 intervention clusters. In control clusters, routine vector control activities were performed. The intervention delivered first, LLIN curtains (from July to August 2013) and secondly, water container covers (from October to March 2014). Cross-sectional entomological surveys were carried out at baseline (February 2013 to June 2013), 9 weeks after the first intervention (August to October 2013), and 4–6 weeks after the second intervention (March to April 2014). Results Curtains were installed in 922 households and water container covers in 303 households. The Breteau index (BI) fell from 14 to 6 in the intervention group and from 8 to 5 in the control group. The additional intervention with LLIN covers for water containers showed a significant reduction in pupae per person index (PPI) (p=0.01). In the intervention group, the PPI index showed a clear decline of 71% compared with 25% in the control group. Costs were high but options for cost savings were identified. Conclusions Short term impact evaluation indicates that the intervention package can reduce dengue vector density but sustained effect will depend on multiple factors. PMID:25604762

  20. Long-lasting insecticide-treated house screens and targeted treatment of productive breeding-sites for dengue vector control in Acapulco, Mexico.

    PubMed

    Che-Mendoza, Azael; Guillermo-May, Guillermo; Herrera-Bojórquez, Josué; Barrera-Pérez, Mario; Dzul-Manzanilla, Felipe; Gutierrez-Castro, Cipriano; Arredondo-Jiménez, Juan I; Sánchez-Tejeda, Gustavo; Vazquez-Prokopec, Gonzalo; Ranson, Hilary; Lenhart, Audrey; Sommerfeld, Johannes; McCall, Philip J; Kroeger, Axel; Manrique-Saide, Pablo

    2015-02-01

    Long-lasting insecticidal net screens (LLIS) fitted to domestic windows and doors in combination with targeted treatment (TT) of the most productive Aedes aegypti breeding sites were evaluated for their impact on dengue vector indices in a cluster-randomised trial in Mexico between 2011 and 2013. Sequentially over 2 years, LLIS and TT were deployed in 10 treatment clusters (100 houses/cluster) and followed up over 24 months. Cross-sectional surveys quantified infestations of adult mosquitoes, immature stages at baseline (pre-intervention) and in four post-intervention samples at 6-monthly intervals. Identical surveys were carried out in 10 control clusters that received no treatment. LLIS clusters had significantly lower infestations compared to control clusters at 5 and 12 months after installation, as measured by adult (male and female) and pupal-based vector indices. After addition of TT to the intervention houses in intervention clusters, indices remained significantly lower in the treated clusters until 18 (immature and adult stage indices) and 24 months (adult indices only) post-intervention. These safe, simple affordable vector control tools were well-accepted by study participants and are potentially suitable in many regions at risk from dengue worldwide. © The author 2015. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.

  1. How long-lasting is the post-conflict slowing after incongruent trials? Evidence from the Stroop, Simon, and flanker tasks.

    PubMed

    Rey-Mermet, Alodie; Meier, Beat

    2017-10-01

    The purpose of the present study was to determine how long-lasting the post-conflict slowing following incongruent stimuli is. In previous research, incongruent stimuli have been used to induce a conflict because they have relevant features for two different response alternatives. So far, the post-conflict slowing following incongruent stimuli has mainly been assessed up to one trial. In the first two experiments, we assessed the persistence of the post-conflict slowing across several trials. To this end, we presented a few incongruent stimuli among non-conflict stimuli. The results showed a consistent slowing for the first few trials immediately following the incongruent trials. In addition, a sporadic slowing was still found on later trials. In two subsequent experiments, we investigated to what extent the infrequency of incongruent trials - rather than their conflict - induced this slowing. To determine this, we used the same design as in the first two experiments, but we presented non-conflict stimuli as infrequent stimuli. The results showed a slowing on one subsequent trial, ruling out the possibility that the post-conflict slowing following incongruent trials was only caused by infrequency. Together, the findings of the present study indicate that the conflict induced by incongruent trials can have a longer lasting impact on subsequent trials than previously thought.

  2. Tunable long lasting phosphorescence due to the selective energy transfer from defects to luminescent centres via tunnelling in Mn(2+) and Tm(3+) co-doped zinc pyrophosphate.

    PubMed

    Pang, Ran; Jia, Yonglei; Zhao, Ran; Li, Haifeng; Fu, Jipeng; Sun, Wenzhi; Jiang, Lihong; Zhang, Su; Li, Chengyu; Su, Qiang

    2014-07-07

    A series of new phosphors Zn2(0.97-x)P2O7:0.06Tm(3+),2xMn(2+) (0 ≤ x ≤ 0.05) were synthesized and their luminescence properties were investigated. The results showed that the defects in all the phosphors were related to Tm(3+), and Mn(2+) merely served as the emission centres. Tm(3+) also acted as an emission centre and yielded blue phosphorescence corresponding to its characteristic f-f emissions in the phosphors where the Mn(2+) concentration was low (x ≤ 0.001), while in the phosphors with high concentrations of Mn(2+) it mainly served as a defect by forming Tm. The electrons thermally released from defects selectively transferred to Mn(2+) centres mainly through thermally-assisted tunnelling and this resulted in their red to near-infrared phosphorescence. By adjusting the ratio of Mn(2+) to Tm(3+) to control the spectral distribution, tunable long lasting phosphorescence from blue to near-infrared was achieved.

  3. d,l-Sotalol at Therapeutic Concentrations Facilitates the Occurrence of Long-lasting Non-stationary Reentry During Ventricular Fibrillation in Isolated Rabbit Hearts

    PubMed Central

    Hsieh, Yu-Cheng; Horng, Tzyy-Leng; Lin, Shien-Fong; Lin, Tung-Chao; Ting, Chih-Tai; Wu, Tsu-Juey

    2011-01-01

    Background Effects of d,l-sotalol at therapeutic concentrations (≤10 mg/L) on wavefront dynamics during ventricular fibrillation (VF) and electrophysiological heterogeneity remain unclear. Methods and Results By using an optical mapping system, epicardial activation patterns of VF were studied in 6 Langendorff-perfused rabbit hearts at baseline, during 10 mg/L d,l-sotalol infusion, and after washout. An additional 4 hearts, action potential duration (APD), conduction velocity, and wavelength (WL) restitutions were determined. During d,l-sotalol infusion, VF was terminated in 3 of the 6 hearts. Only one experienced a transient ventricular tachycardia (VT). d,l-Sotalol reduced the number of phase singularities (i.e., wavebreak) during VF (p<0.05). d,l-Sotalol also increased the occurrence frequency (p<0.05) and life span (p<0.05) of epicardial reentry during VF. These reentries were non-stationary in nature and did not anchor on anatomical structures. Restitution data showed that d,l-Sotalol flattened APD restitution. Furthermore, APD dispersion and spatial heterogeneity of restitutions were not enhanced by d,l-sotalol. Conclusions d,l-Sotalol at therapeutic concentrations decreased wavebreak and facilitated the occurrence of long-lasting non-stationary reentry during VF. However, VT rarely occurred. The related mechanisms include: (1) APD restitution flattening without enhancement of spatial heterogeneity of electrophysiological properties causes wavefront organization, and (2) WL prolongation prevents a steady anchoring of reentry. PMID:19008631

  4. Efficacy of Olyset® Plus, a New Long-Lasting Insecticidal Net Incorporating Permethrin and Piperonil-Butoxide against Multi-Resistant Malaria Vectors

    PubMed Central

    Pennetier, Cédric; Bouraima, Aziz; Chandre, Fabrice; Piameu, Michael; Etang, Josiane; Rossignol, Marie; Sidick, Ibrahim; Zogo, Barnabas; Lacroix, Marie-Noëlle; Yadav, Rajpal; Pigeon, Olivier; Corbel1, Vincent

    2013-01-01

    Due to the rapid extension of pyrethroid resistance in malaria vectors worldwide, manufacturers are developing new vector control tools including insecticide mixtures containing at least two active ingredients with different mode of action as part of insecticide resistance management. Olyset® Plus is a new long-lasting insecticidal net (LLIN) incorporating permethrin and a synergist, piperonyl butoxide (PBO), into its fibres in order to counteract metabolic-based pyrethroid resistance of mosquitoes. In this study, we evaluated the efficacy of Olyset® Plus both in laboratory and field against susceptible and multi-resistant malaria vectors and compared with Olyset Net, which is a permethrin incorporated into polyethylene net. In laboratory, Olyset® Plus performed better than Olyset® Net against susceptible Anopheles gambiae strain with a 2-day regeneration time owing to an improved permethrin bleeding rate with the new incorporation technology. It also performed better than Olyset® Net against multiple resistant populations of An. gambiae in experimental hut trials in West Africa. Moreover, the present study showed evidence for a benefit of incorporating a synergist, PBO, with a pyrethroid insecticide into mosquito netting. These results need to be further validated in a large-scale field trial to assess the durability and acceptability of this new tool for malaria vector control. PMID:24116029

  5. Emergence and long-lasting persistence of linezolid-resistant Enterococcus faecium-ST117 in an oncohematologic patient after a nine-day course of linezolid.

    PubMed

    Sánchez-Díaz, Ana María; Cuartero, Claudio; Lozano, Sara; Rodríguez, Juan Diego; Alonso, Juan Manuel; Quiles-Melero, Inmaculada; López, Javier; Cantón, Rafael; Ruiz-Garbajosa, Patricia

    2014-02-01

    We report the emergence and long-lasting persistence of linezolid resistance in an ampicillin-resistant Enterococcus faecium strain in the intestine of a neutropenic oncohematologic patient receiving chemotherapy. The patient was first colonized by an epidemic ampicillin-resistant E. faecium (ARE)-ST117 clustering into lineage 78. This clone exhibited resistance to levofloxacin, erythromycin and high-level resistance to streptomycin and gentamicin. After receiving treatment with several broad spectrum antibiotics for febrile neutropenia, a 9-day course of oral linezolid was administered once the patient developed bacteraemia by the same ARE colonizing clone. Linezolid-resistant ARE was detected 17 days later in the follow-up fecal samples and persisted 41 days after suppression of linezolid therapy. Resistance to linezolid was associated with G2576T transversion in the 23S rRNA and the presence of cfr gene was not detected. The persistence of G2576T-ARE strains, especially in oncohematologic patients with injured intestinal membranes, could increase the risk of bacteraemia.

  6. Evaluation of Polyethylene-Based Long Lasting Treated Bed Net Netprotect on Anopheles Mosquitoes, Malaria Incidence, and Net Longivity in Western Kenya

    PubMed Central

    Odhiambo, M. T. O.; Skovmand, O.; Vulule, J. M.; Kokwaro, E. D.

    2013-01-01

    We studied the effect on malaria incidence, mosquito abundance, net efficacy, net use rate, chemical analysis, and holes of a long lasting insecticide treated bed net (Netprotect) in western Kenya, 2007–2010. Nets were hung in 150 households 6 months before they were hung in a second, 2 km away. Indoor resting densities were monitored by pyrethrum spray catch and malaria cases by passive detection using clinical manifestations and rapid diagnostic test. The probability of finding An. arabiensis in the control area was 2.6 times higher than that in intervention area during the first 6 months. Human blood feeding index of Anopheles funestus declined 17%. After bed nets were hung in the second area, malaria incidence declined 25% down to the level in the first area. Incidence remained at this low level for 2 years. 90% of collected nets were efficacious after 3-year use. Deltamethrin dosage declined from 1.9 to 0.5 g/kg over 3 years. Attrition rate after 3 years was 21%. WHO hole index changed from 333 to 114 to 381 over the three years. This index summarizes the numbers of holes in size categories and multiplies with the mean hole area per category. It is very sensitive to the impact of big holes in a few nets. PMID:24194770

  7. School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania

    PubMed Central

    Lalji, Shabbir; Ngondi, Jeremiah M; Thawer, Narjis G; Tembo, Autman; Mandike, Renata; Mohamed, Ally; Chacky, Frank; Mwalimu, Charles D; Greer, George; Kaspar, Naomi; Kramer, Karen; Mlay, Bertha; Issa, Kheri; Lweikiza, Jane; Mutafungwa, Anold; Nzowa, Mary; Willilo, Ritha A; Nyoni, Waziri; Dadi, David; Ramsan, Mahdi M; Reithinger, Richard; Magesa, Stephen M

    2016-01-01

    ABSTRACT Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country’s Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania. PMID:27353618

  8. The impact of long-lasting preemptive epidural analgesia before total hip replacement on the hormonal stress response. A prospective, randomized, double-blind study.

    PubMed

    Al Oweidi, Abdelkarim S; Klasen, Joachim; Al-Mustafa, Mahmoud M; Abu-Halaweh, Sami A; Al-Zaben, Khaled R; Massad, Islam M; Qudaisat, Ibrahim Y

    2010-06-01

    Recent studies suggest that preemptive analgesia may be effective in reducing postoperative pain. One physiologic explanation may be interference with the endogenous opioid response. We investigated whether long-lasting preoperative preemptive analgesia may have an effect on the hormonal stress response after total hip replacement. 42 patients scheduled for elective hip replacement for coxarthrosis were randomized to receive, on the day before the operation, either 5 ml*h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml*h(-1) saline (control group, n = 21). Postoperative analgesia was achieved in both groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The main outcome measure was the concentration of authentic beta-endorphin [1-31] in plasma up to 4 days after surgery. Additional parameters included concentrations of adrenocorticotrope hormone and cortisol. Both groups were comparable concerning preoperative parameters and pain scores. Epidural blocks were sufficient in all patients for operative analgesia. Preemptive analgesia was performed for 11-20 hours in both groups and led to significantly decreased pain scores before surgery. Preemptive analgesia with epidural ropivacaine did not lead to decreased concentrations of beta-endorphin [1-31] before the start of surgery or in the postoperative period. Furthermore, no differences could be detected in the time course of beta-endorphin and adrenocorticotrope hormone after surgery. However, cortisol concentrations differed significantly between groups before the operation, but showed a comparable rise after surgery. Differences in postoperative pain after preemptive analgesia do not seem to be due to an altered endogenous opioid response.

  9. Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex.

    PubMed

    Peinemann, Alexander; Reimer, Bibiana; Löer, Christian; Quartarone, Angelo; Münchau, Alexander; Conrad, Bastian; Siebner, Hartwig Roman

    2004-07-01

    To study the after effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) on corticospinal excitability. Eight healthy volunteers received either 150 or 1800 stimuli of 5 Hz rTMS on two separate days in a counterbalanced order. rTMS was given over the 'motor hot spot' of the right first dorsal interosseus (FDI) muscle using an intensity of 90% of resting motor threshold (referred to as subthreshold rTMS). We evaluated the amplitude of the motor-evoked potential (MEP), short-latency intracortical inhibition (SICI), short-latency intracortical facilitation (SICF), and cortical silent period (CSP) before and for about 30 min after rTMS. MEPs were recorded from the right FDI muscle and abductor digiti minimi (ADM) muscle. 1800 stimuli induced an increase in MEP amplitude in the relaxed FDI muscle, but not in the relaxed ADM muscle. This facilitatory after effect was stable for at least 30 min. Prolonged 5 Hz rTMS had no effect on the relative magnitude of SICI and SICF. 150 stimuli caused no lasting modulation of MEP amplitudes in either muscle. In a subgroup of 5 subjects, 900 conditioning stimuli caused only a short-lived MEP facilitation. 5 Hz rTMS did not modify the duration of the CSP during tonic contraction. A single session of subthreshold 5 Hz rTMS to the M1 can induce a long-lasting and muscle-specific increase in resting corticospinal excitability. However, a sufficient number of conditioning stimuli is necessary to produce persistent corticospinal facilitation.

  10. Effectiveness of a novel long-lasting pyriproxyfen larvicide (SumiLarv®2MR) against Aedes mosquitoes in schools in Yangon, Myanmar.

    PubMed

    Oo, Sai Zaw Min; Thaung, Sein; Maung, Yan Naung Maung; Aye, Khin Myo; Aung, Zar Zar; Thu, Hlaing Myat; Thant, Kyaw Zin; Minakawa, Noboru

    2018-01-06

    Mosquito-borne diseases are prevalent in Myanmar, with the number of dengue cases showing a significant increase in recent years. Dengue vectors have developed resistance to insecticides and currently used larvicides show only short-term effectiveness. As a result, an alternative larvicide is urgently needed. The present study evaluated the larvicidal effectiveness of long-lasting pyriproxyfen resin discs (SumiLarv®2MR) against dengue virus vectors in schools in Hlaing Thar Yar Township, Yangon. The proportion of Aedes mosquito-infested containers was significantly reduced in the schools applied with the larvicide (OR: 0.24, 95% CI: 0.12-0.48) while there was little reduction noted in the control schools (OR: 0.97, 95% CI: 0.55-1.72). The density of infested containers was also significantly reduced in the intervention schools (Beta: -1.50, 95% CI: -1.98- -1.04), but there was no significant reduction in density in the control schools (Beta: -0.19, 95% CI: -0.53-0.14). The proportion of adult emergence was less than 20% in the treated water collected from the intervention schools for six months, while the proportion was over 90% in the untreated water. In addition, eight-month-old SumiLarv®2MR resin discs were still 100% effective when tested in the laboratory. More than 50% of the discs disappeared from treated containers within two months of intervention. SumiLarv®2MR was effective in reducing Aedes-infested containers at least six months after its application in schools. This new pyriproxyfen formulation has great potential for improving the current dengue vector control program in Myanmar.

  11. Genetically modified rabies virus ERA strain is safe and induces long-lasting protective immune response in dogs after oral vaccination.

    PubMed

    Shuai, Lei; Feng, Na; Wang, Xijun; Ge, Jinying; Wen, Zhiyuan; Chen, Weiye; Qin, Lide; Xia, Xianzhu; Bu, Zhigao

    2015-09-01

    Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG333E) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) were generated by reverse genetic. The recombinant virus rERAG333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12months after immunization. Dogs received oral vaccination with rERAG333E induced strong protective RABV VNA response, which lasted for over 3years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Pathologic Features of Parathyroid Glands Associated With the Pathogenesis of Long-lasting Persistent Hyperparathyroidism After Kidney Transplantation in Long-term Dialysis Patients.

    PubMed

    Nakamura, M; Ishida, H; Takiguchi, S; Tanaka, K; Marui, Y

    2016-04-01

    Persistent hyperparathyroidism in kidney transplant recipients may be prolonged for a few years, and in these cases, parathyroidectomy is indicated even if graft function is satisfactory. The aim of this study was to characterize the parathyroid glands in long-term dialysis recipients and determine the pathogenesis of persistent hyperparathyroidism. We analyzed 44 parathyroid glands resected from 11 patients who underwent parathyroidectomy after kidney transplantation. The histopathologic types and weights of all the parathyroid glands were evaluated. The mean dialysis period was 15.8 years, and the time from kidney transplantation to parathyroidectomy ranged from 3.5 to 89 months. Nodular hyperplasia was present in parathyroid glands in all cases. The mean glandular weight was 396.0 ± 299.0 mg, and the maximum glandular weight was 3200 mg. Seven patients who underwent parathyroidectomy >1 year after kidney transplantation (late PT) were compared with 4 patients who underwent parathyroidectomy within 10 months after transplantation (early PT). The maximum (442.9 vs 1503 mg; P = .018) and mean (312.5 ± 177.4 mg vs 1135.6 ± 977.7 mg; P = .001) glandular weights were significantly lower in patients who underwent late PT compared with those who received early PT. Based on the histopathologic type and glandular weight of each parathyroid gland, nodular hyperplasia in glands ≤150 mg was common in patients who underwent late PT. The presence of nodular hyperplasia in parathyroid glands with a low weight may be involved in long-lasting persistent hyperparathyroidism in patients undergoing long-term dialysis. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Social Determinants of Long Lasting Insecticidal Hammock-Use Among the Ra-Glai Ethnic Minority in Vietnam: Implications for Forest Malaria Control

    PubMed Central

    Muela Ribera, Joan; Ngo Duc, Thang; van Bortel, Wim; Truong Ba, Nhat; Van, Ky Pham; Le Xuan, Hung; D'Alessandro, Umberto; Erhart, Annette

    2012-01-01

    Background Long-lasting insecticidal hammocks (LLIHs) are being evaluated as an additional malaria prevention tool in settings where standard control strategies have a limited impact. This is the case among the Ra-glai ethnic minority communities of Ninh Thuan, one of the forested and mountainous provinces of Central Vietnam where malaria morbidity persist due to the sylvatic nature of the main malaria vector An. dirus and the dependence of the population on the forest for subsistence - as is the case for many impoverished ethnic minorities in Southeast Asia. Methods A social science study was carried out ancillary to a community-based cluster randomized trial on the effectiveness of LLIHs to control forest malaria. The social science research strategy consisted of a mixed methods study triangulating qualitative data from focused ethnography and quantitative data collected during a malariometric cross-sectional survey on a random sample of 2,045 study participants. Results To meet work requirements during the labor intensive malaria transmission and rainy season, Ra-glai slash and burn farmers combine living in government supported villages along the road with a second home at their fields located in the forest. LLIH use was evaluated in both locations. During daytime, LLIH use at village level was reported by 69.3% of all respondents, and in forest fields this was 73.2%. In the evening, 54.1% used the LLIHs in the villages, while at the fields this was 20.7%. At night, LLIH use was minimal, regardless of the location (village 4.4%; forest 6.4%). Discussion Despite the free distribution of insecticide-treated nets (ITNs) and LLIHs, around half the local population remains largely unprotected when sleeping in their forest plot huts. In order to tackle forest malaria more effectively, control policies should explicitly target forest fields where ethnic minority farmers are more vulnerable to malaria. PMID:22253852

  14. Comparison of efficacy of five types of long-lasting insecticidal nets against Anopheles fluviatilis, the primary malaria vector in east-central India.

    PubMed

    Gunasekaran, K; Sahu, S S; Vijayakumar, T; Vaidyanathan, K; Yadav, R S; Pigeon, O; Jambulingam, P

    2014-07-01

    Five types of long-lasting insecticidal nets (LNs), namely, Olyset, Netprotect, PermaNet, DuraNet, and Interceptor, were tested after 20 washes for efficacy in terms of mortality, deterrence effect, blood-feeding inhibition, and induced exophily of the malaria vector Anopheles fluviatilis in experimental huts in Malkangiri district of Odisha State, India. Efficacy of the three synthetic pyrethroids (SPs) used in the LNs was also analyzed. Use of LNs reduced the entry of An. fluviatilis into the huts by 73.3-83.2%, and the five LNs were comparable in terms of deterrence. The exit rate of An. fluviatilis from the huts with untreated net was 56.3%, and relative to this, Olyset followed by DuraNet induced significantly a higher exophily. In contrast, the exit rate was significantly lower with Interceptor. Among the three SPs, permethrin induced significantly greater exophily relative to the untreated control, and as a result of this, permethrin-treated Olyset produced a lower mortality. Blood-feeding rate of An. fluviatilis was significantly lower with all the five LNs than the control. Similarly, all the three SPs significantly inhibited blood feeding compared with the control. Interceptor and DuraNet, both alphacypermethrin-treated LNs, caused relatively a higher mortality of An. fluviatilis than the other LNs. The five brands of LNs and three SPs tested in the current study were equally effective in terms of deterrence and blood-feeding inhibition; only exiting and killing effect differed among them. Permethrin-treated LNs induced greater exophily, while, overall, alphacypermethrin-treated LNs killed more An. fluviatilis that entered the huts. Advantage of deterrence, excito-repellent, and killing effects of LNs and appropriate selection of SP for net treatment are discussed in this paper.

  15. A Novel Delta Opioid Receptor Antagonist, SoRI-9409, Produces a Selective and Long-Lasting Decrease in Ethanol Consumption in Heavy-Drinking Rats

    PubMed Central

    Nielsen, Carsten K.; Simms, Jeffrey A.; Pierson, Haley B.; Li, Rui; Saini, Surendra K.; Ananthan, Subramaniam; Bartlett, Selena E.

    2013-01-01

    Background Naltrexone, a compound with high affinity for the μ opioid receptor (MOP-R) reduces alcohol consumption. SoRI-9409 is a derivative of naltrexone that has highest affinity at δ opioid receptors (DOP-Rs). We have investigated the effects of SoRI-9409 on ethanol consumption to determine the consequences of altering the naltrexone compound to a form with increased efficacy at DOP-Rs. Methods Effects of the opioid receptor antagonists, SoRI-9409 (0–30 mg/kg, IP), naltrexone (0–30 mg/kg, IP), or naltrindole (0–10 mg/kg, IP) on ethanol consumption was measured in high- and low-ethanol–consuming rats with two different drinking paradigms. SoRI-9409-, naltrexone-, and naltrindole-mediated inhibition of DOP-R–stimulated [35S]GTPγS binding was measured in brain membranes prepared from high-ethanol–consuming rats. The effects of SoRI-9409 on morphine-mediated analgesia, conditioned place preference, and anxiety were also examined. Results In high- but not low-ethanol–consuming animals, SoRI-9409 is threefold more effective and selective at reducing ethanol consumption when compared with naltrexone or naltrindole for up to 24 hours. SoRI-9409 administered daily for 28 days continuously reduced ethanol consumption, and when the administration of SoRI-9409 was terminated, the amount of ethanol consumed remained lower compared with vehicle-treated animals. Furthermore, SoRI-9409 inhibits DOP-R–stimulated [35S]GTPγS binding in brain membranes of high-ethanol–consuming rats. Conclusions SoRI-9409 causes selective and long-lasting reductions of ethanol consumption. This suggests that compounds that have high affinity for DOP-Rs such as SoRI-9409 might be promising candidates for development as a novel therapeutic for the treatment of alcoholism. PMID:18774553

  16. A novel delta opioid receptor antagonist, SoRI-9409, produces a selective and long-lasting decrease in ethanol consumption in heavy-drinking rats.

    PubMed

    Nielsen, Carsten K; Simms, Jeffrey A; Pierson, Haley B; Li, Rui; Saini, Surendra K; Ananthan, Subramaniam; Bartlett, Selena E

    2008-12-01

    Naltrexone, a compound with high affinity for the mu opioid receptor (MOP-R) reduces alcohol consumption. SoRI-9409 is a derivative of naltrexone that has highest affinity at delta opioid receptors (DOP-Rs). We have investigated the effects of SoRI-9409 on ethanol consumption to determine the consequences of altering the naltrexone compound to a form with increased efficacy at DOP-Rs. Effects of the opioid receptor antagonists, SoRI-9409 (0-30 mg/kg, IP), naltrexone (0-30 mg/kg, IP), or naltrindole (0-10 mg/kg, IP) on ethanol consumption was measured in high- and low-ethanol-consuming rats with two different drinking paradigms. SoRI-9409-, naltrexone-, and naltrindole-mediated inhibition of DOP-R-stimulated [(35)S]GTP gamma S binding was measured in brain membranes prepared from high-ethanol-consuming rats. The effects of SoRI-9409 on morphine-mediated analgesia, conditioned place preference, and anxiety were also examined. In high- but not low-ethanol-consuming animals, SoRI-9409 is threefold more effective and selective at reducing ethanol consumption when compared with naltrexone or naltrindole for up to 24 hours. SoRI-9409 administered daily for 28 days continuously reduced ethanol consumption, and when the administration of SoRI-9409 was terminated, the amount of ethanol consumed remained lower compared with vehicle-treated animals. Furthermore, SoRI-9409 inhibits DOP-R-stimulated [(35)S]GTP gamma S binding in brain membranes of high-ethanol-consuming rats. SoRI-9409 causes selective and long-lasting reductions of ethanol consumption. This suggests that compounds that have high affinity for DOP-Rs such as SoRI-9409 might be promising candidates for development as a novel therapeutic for the treatment of alcoholism.

  17. Scale-up of a programme for malaria vector control using long-lasting insecticide-treated nets: lessons from South Sudan

    PubMed Central

    Remijo, Constantino D; Pasquale, Harriet; Baba, Samson P; Lako, Richard L

    2014-01-01

    Abstract Problem Long-lasting insecticidal nets (LLINs) are important tools in malaria control. South Sudan, like many other endemic countries, has struggled to improve LLIN coverage and utilization. Approach In 2006, Southern Sudan – known as South Sudan after independence in 2011 – initiated a strategic plan to increase LLIN coverage so that at least 60% of households had at least one LLIN each. By 2008, the target coverage was 80% of households and the Global Fund had financed a phased scale-up of LLIN distribution in the region. Local setting South Sudan’s entire population is considered to be at risk of malaria. Poor control of the vectors and the large-scale movements of returnees, internally displaced people and refugees have exacerbated the problem. Relevant changes By 2012, approximately 8.0 million LLINs had been distributed in South Sudan. Between 2006 and 2009, the percentage of households possessing at least one LLIN increased from about 12% to 53% and LLIN utilization rates increased from 5 to 25% among children younger than 5 years and from 5 to 36% among pregnant women. The number of recorded malaria cases increased from 71 948 in 2008 to 1 198 357 in 2012. Lessons learnt In post-conflict settings, a phased programme for the national scale-up of LLIN coverage may not have a substantial impact. A nationwide campaign that is centrally coordinated and based on sound guidelines may offer greater benefits. A strong partnership base and effective channels for the timely and supplementary deployment of LLINs may be essential for universal coverage. PMID:24700997

  18. Chronic stress leads to long-lasting deficits in olfactory-guided behaviors, and to neuroplastic changes in the nucleus of the lateral olfactory tract.

    PubMed

    Vaz, Ricardo P; Cardoso, Armando; Serrão, Paula; Pereira, Pedro A; Madeira, M Dulce

    2018-01-04

    A recent study reported that the integrity of the nucleus of the lateral olfactory tract (nLOT) is required for normal olfaction and for the display of odor-driven behaviors that are critical for species survival and reproduction. In addition to being bi-directionally connected with a key element of the neural circuitry that mediates stress response, the basolateral nucleus of the amygdala, the nLOT is a potential target for glucocorticoids as its cells express glucocorticoid receptors. Herein, we have addressed this hypothesis by exploring, first, if chronic variable stress (CVS) disrupts odor detection and discrimination, and innate olfactory-driven behaviors, namely predator avoidance, sexual behavior and aggression in male rats. Next, we examined if CVS alters the nLOT structure and if such changes can be ascribed to stress-induced effects on the activity of the main output neurons, which are glutamatergic, and/or of local GABAergic interneurons. Finally, we analyzed if the stress-induced changes are transient or, conversely, persist after cessation of CVS exposure. Our data demonstrate that CVS leads to severe olfactory deficits with inability to detect and discriminate between odors and to innately avoid predator odors. No effects of CVS on sexual and aggressive behaviors were observed. Results also showed that CVS leads to somatic hypertrophy of pyramidal glutamatergic neurons, which likely results from neuronal disinhibition consequent to the loss of inhibitory inputs mediated by GABAergic interneurons. Most of the CVS-induced effects persist beyond a 4-week stress-free period, suggesting long-lasting effects of chronic stress on the structure and function of the olfactory system. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. A new long-lasting indoor residual formulation of the organophosphate insecticide pirimiphos methyl for prolonged control of pyrethroid-resistant mosquitoes: an experimental hut trial in Benin.

    PubMed

    Rowland, Mark; Boko, Pelagie; Odjo, Abibatou; Asidi, Alex; Akogbeto, Martin; N'Guessan, Raphael

    2013-01-01

    Indoor residual spraying (IRS) is widely used for malaria transmission control in sub-Saharan Africa. Resistance to pyrethroids in the mosquito Anopheles gambiae is a growing problem. There is an urgent need to develop long-lasting alternative insecticides to reduce selection pressure for pyrethroid resistance and to provide control with a single IRS application in countries with long transmission seasons. Two capsule suspension formulations (CS) of the organophosphate pirimiphos methyl were evaluated as IRS treatments in experimental huts in an area of Benin where the mosquitoes Anopheles gambiae and Culex quinquefasciatus are resistant to pyrethroids but susceptible to organophosphates. The CS formulations were tested alongside an emulsifiable concentrate (EC) formulation of pirimiphos methyl and a CS formulation of the pyrethroid lambdacyhalothrin. The two CS formulations of pirimiphos methyl gave prolonged control of An. gambiae and Cx. quinquefasciatus. In cement huts application rates of 0.5 g/m(2) induced high mortality of An. gambiae for almost a year: overall mortality rates 87% (95% CI 82-91%) and 92% (95% CI 88-94%). In mud huts application rates of 1 g/m(2) induced high mortality of An. gambiae for 10 months: overall mortality rates 75% (95% CI 69-81%) and 76% (95% CI 68-83%). The EC formulation of pirimiphos methyl failed to control An. gambiae two months after spraying. The pyrethroid lambdacyhalothrin demonstrated prolonged residual activity in bioassay tests but failed to control pyrethroid resistant An. gambiae that entered the huts. Pirimiphos methyl CS was highly active against Culex quinquefasciatus and gave control for 10 months in cement huts and 6 months in mud huts. Pirimiphos methyl CS (Actellic 300 CS) applied at 1 g/m(2) shows great promise for providing prolonged control of pyrethroid-resistant An gambiae and for delaying pyrethroid resistance. An alternative to DDT, giving year-round transmission control in sub-Saharan Africa is now a

  20. Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen.

    PubMed

    Andersen, Rikke; Donia, Marco; Ellebaek, Eva; Borch, Troels Holz; Kongsted, Per; Iversen, Trine Zeeberg; Hölmich, Lisbet Rosenkrantz; Hendel, Helle Westergren; Met, Özcan; Andersen, Mads Hald; Thor Straten, Per; Svane, Inge Marie

    2016-08-01

    Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Long-lasting sensitization induced by repeated risperidone treatment in adolescent Sprague-Dawley rats: A possible D2 receptor mediated phenomenon?

    PubMed Central

    Zhang, Qinglin; Hu, Gang; Li, Ming

    2014-01-01

    Rationale Risperidone use in children and adolescents for the treatment of various neuropsychiatric disorders (e.g. schizophrenia, autism, disruptive behavior, etc.) has increased substantially in recent decades. However, its long-term effect on the brain and behavioral functions is not well understood. Objective The present study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response in adulthood in the conditioned avoidance response and PCP-induced hyperlocomotion tests. Methods Male adolescent Sprague-Dawley rats (postnatal days [P] 40-44 or 43-48) were first treated with risperidone (0.3, 0.5 or 1.0 mg/kg, sc) and tested in the conditioned avoidance or PCP (3.2 mg/kg, sc)-induced hyperlocomotion model daily for 5 consecutive days. After they became adults (~P 76-80), they were challenged with risperidone (0.3 mg/kg, sc) to assess their sensitivity to risperidone re-exposure. A quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test was later conducted to assess the risperidone-induced functional changes in D2 receptor. Results In the risperidone challenge test in adulthood, adult rats previously treated with risperidone in adolescence made significantly fewer avoidance responses and exhibited significantly lower PCP-induced hyperlocomotion than those previously treated with vehicle. They also appeared to be more hyperactive than the vehicle-pretreated ones in the quinpirole-induced hyperlocomotion test. Prepulse inhibition of acoustic startle or fear-induced 22 kHz ultrasonic vocalizations in adulthood was not altered by adolescence risperidone treatment. Conclusions Adolescent risperidone exposure induces a long-term increase in behavioral sensitivity to risperidone that persists into adulthood. This long-lasting change might be due to functional upregulation of D2-mediated neurotransmission. PMID:24363078

  2. Galantamine prevents long-lasting suppression of excitatory synaptic transmission in CA1 pyramidal neurons of soman-challenged guinea pigs.

    PubMed

    Alexandrova, E A; Alkondon, M; Aracava, Y; Pereira, E F R; Albuquerque, E X

    2014-09-01

    Galantamine, a drug currently approved for the treatment of Alzheimer's disease, has recently emerged as an effective pretreatment against the acute toxicity and delayed cognitive deficits induced by organophosphorus (OP) nerve agents, including soman. Since cognitive deficits can result from impaired glutamatergic transmission in the hippocampus, the present study was designed to test the hypothesis that hippocampal glutamatergic transmission declines following an acute exposure to soman and that this effect can be prevented by galantamine. To test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were recorded from CA1 pyramidal neurons in hippocampal slices obtained at 1h, 24h, or 6-9 days after guinea pigs were injected with: (i) 1×LD50 soman (26.3μg/kg, s.c.); (ii) galantamine (8mg/kg, i.m.) followed 30min later by 1×LD50 soman, (iii) galantamine (8mg/kg, i.m.), or (iv) saline (0.5ml/kg, i.m.). In soman-injected guinea pigs that were not pretreated with galantamine, the frequency of EPSCs was significantly lower than that recorded from saline-injected animals. There was no correlation between the severity of soman-induced acute toxicity and the magnitude of soman-induced reduction of EPSC frequency. Pretreatment with galantamine prevented the reduction of EPSC frequency observed at 6-9 days after the soman challenge. Prevention of soman-induced long-lasting reduction of hippocampal glutamatergic synaptic transmission may be an important determinant of the ability of galantamine to counter cognitive deficits that develop long after an acute exposure to the nerve agent. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Galantamine Prevents Long-Lasting Suppression of Excitatory Synaptic Transmission in CA1 Pyramidal Neurons of Soman-Challenged Guinea Pigs

    PubMed Central

    Alexandrova, E. A.; Alkondon, M.; Aracava, Y.; Pereira, E. F. R.; Albuquerque, E. X.

    2014-01-01

    Galantamine, a drug currently approved for treatment of Alzheimer's disease, has recently emerged as an effective pretreatment against the acute toxicity and delayed cognitive deficits induced by organophosphorus (OP) nerve agents, including soman. Since cognitive deficits can result from impaired glutamatergic transmission in the hippocampus, the present study was designed to test the hypothesis that hippocampal glutamatergic transmission declines following an acute exposure to soman and that this effect can be prevented by galantamine. To test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were recorded from CA1 pyramidal neurons in hippocampal slices obtained at 1 h, 24 h, or 6-9 days after guinea pigs were injected with: (i) 1xLD50 soman (26.3 μg/kg, s.c.); (ii) galantamine (8 mg/kg, i.m.) followed 30 min later by 1xLD50 soman, (iii) galantamine (8 mg/kg, i.m.), or (iv) saline (0.5 ml/kg, i.m.). In soman-injected guinea pigs that were not pretreated with galantamine, the frequency of EPSCs was significantly lower than that recorded from saline-injected animals. There was no correlation between the severity of soman-induced acute toxicity and the magnitude of soman-induced reduction of EPSC frequency. Pretreatment with galantamine prevented the reduction of EPSC frequency observed at 6-9 days after the soman challenge. Prevention of soman-induced long-lasting reduction of hippocampal glutamatergic synaptic transmission may be an important determinant of the ability of galantamine to counter cognitive deficits that develop long after an acute exposure to the nerve agent. PMID:25064080

  4. Hyaluronic Acid Filler Injections Under the Metatarsal Heads Provide a Significant and Long-Lasting Improvement in Metatarsalgia From Wearing High-Heeled Shoes.

    PubMed

    Foumenteze, Jean Paul; Simpson, Helen; Kerrouche, Nabil

    2018-01-22

    Metatarsalgia is a common overuse injury that may be caused by wearing high-heeled shoes. To evaluate the decrease in metatarsalgia using a hyaluronic acid dermal filler. A 6-month, open study was conducted in 15 subjects with metatarsalgia because of regularly wearing high-heeled shoes. Hyaluronic acid (20 mg/mL) with lidocaine hydrochloride (3 mg/mL) was injected under the metatarsal heads at baseline. Pain (on a 0-10 scale) under the metatarsal heads when walking in high heels was recorded in a weekly subject diary. At 6 months after injections, 5 subjects (33.3%) reported no metatarsalgia pain. For subjects with pain, they were able to wear high heels for significantly longer than before the injections (7.2 hours at 6 months vs 3.4 hours at baseline). Significant improvements from baseline were observed at Month 6 for time to onset of pain (3.5 hours longer), time between onset of pain and intolerable pain (1.9 hours longer), and pain sensation (-2.2 grades at onset and -3.8 grades at shoe removal). No adverse events were reported. Injection of hyaluronic acid filler to the forefeet provided a significant effective, long-lasting, and well-tolerated improvement in metatarsalgia because of wearing high-heeled shoes.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  5. Wash resistance and bio-efficacy of Olyset®Plus, a long-lasting insecticide-treated mosquito net with synergist against malaria vector, Anopheles stephensi.

    PubMed

    Sheikhi, Soraya; Vatandoost, Hassan; Abai, Mohammad Reza; Shayeghi, Mansoreh; Raeisi, Ahmad; Akbari, Morteza; Nikpoor, Fatemeh; Aghdam, Mohammad Sistanizade; Bagheri, Akbar

    2017-09-01

    To determine the wash resistance of Olyset ® Plus using World Health Organization Pesticide Evaluation Scheme standard washing procedure and to assess the value of knock down and mortality rates of Anopheles stephensi at different regimens of long lasting insecticide treated nets washings. The study was conducted at the Bioassay Laboratory of Culicidae Insectary, School of Public Health, Tehran University of Medical Sciences, Iran. The net was made of polyester impregnated with permethrin and piperonyl butoxide at a ratio of 2:1. The washing resistance was assessed using Le Chat ® soap and a shaker incubator set at a speed of 155 r/min, 30 °C for 10 min. The cone bioassay test was carried out according to World Health Organization recommended guideline with tolerant field strain of female Anopheles stephensi to pyrethroids. The knockdown and mortality rates of female mosquitoes exposed to Olyset ® Plus from un-washed nets to 2 washings were 79.7% and 88.8% respectively. Mortality was dropped to zero while active ingredient estimated 0.532 μg/100 cm 2 to 0.481 μg/100 cm 2 after 15 washings. A positive correlation was seen between residues of permethrin on nets, knockdown rate and mortality rate of female Anopheles stephensi exposed to different regimes of washed Olyset ® Plus (r = 0.954, P = 0.001). It is recommended that a preliminary survey conducted on resistance level of Anopheles vectors before the distribution of Olyset ® Plus in malaria endemic communities. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  6. A long-lasting protective immunity against chronic toxoplasmosis in mice induced by recombinant rhoptry proteins encapsulated in poly (lactide-co-glycolide) microparticles.

    PubMed

    Xu, Ying; Zhang, Nian-Zhang; Wang, Meng; Dong, Hu; Feng, Sheng-Yong; Guo, Hui-Chen; Zhu, Xing-Quan

    2015-11-01

    Toxoplasma gondii infection in humans and animals is a worldwide zoonosis. Prevention and control of toxoplasmosis based on vaccination is one of the promising strategies. In the present study, recombinant T. gondii rhoptry proteins 38 and 18 (TgROP38 and TgROP18) were encapsulated into poly (lactide-co-glycolide) (PLG) (1:1), respectively, to obtain the stable water-in-oil-in-water double emulsion. Female Kunming mice were then immunized with the protein vaccines twice at a 2-week interval. Eight weeks after the second immunization, 10 mice from each group were challenged with T. gondii PRU strain (genotype II). The entrapment rates of PLG-rROP38 and PLG-rROP18 ranged from 65.5 to 77.7% and 58.1 to 72.3%, respectively. Immunization of mice with rROP38 and rROP18 proteins encapsulated into PLG microparticles elicited strongly humoral and cell-mediated responses against T. gondii, associated with relatively high levels of total IgG, IgG2a isotype, and IFN-γ, as well as the mixed Th1/Th2 immunity responses. Immunization with various protein vaccines induced significant reduction of the brain cysts after chronic infection with the T. gondii PRU strain, and the most effective protection was achieved in the PLG-rROP38-rROP18-immunized mice, with a cyst reduction of 81.3%. The findings of the present study indicated that recombinant rhoptry antigens encapsulated in PLG could maintain the protein immunogenicity in an extended period and elicit effective protection against chronic T. gondii infection, which has implications for the development of long-lasting vaccines against chronic toxoplasmosis in animals.

  7. [A Case of Dengue Fever and Subsequent Long-lasting Depression Accompanied by Alopecia in a Japanese Traveler Returning from Bali, Indonesia].

    PubMed

    Hitani, Akihiro; Yamaya, Waka; To, Masako; Kano, Ichino; Honda-Hosono, Natsue; Takasaki, Tomohiko; Haruki, Kosuke

    2015-03-01

    Recovery from dengue fever is generally rapid and uneventful. However, recuperation is often prolonged and may be accompanied by noticeable depression. We present herein on a traveler to Indonesia who developed long-lasting depression after the classic symptoms of dengue fever such as fever, arthralgia, and macropapular rash had resolved. A previously healthy 42-year old japanese woman presented to the Travel Clinic of Seirei Yokohama Hospital with complaints of 4 days of fever, joint aches, bone pain, and a macropapular rash on her torso. She had returned from Bali 5 days previously. During her 1-week stay, one day was spent in rural, mountainous areas where she was exposed to several mosquito bites. The 1st serum sample collected 4 days after the disease onset gave positive result in the rapid dengue IgM antibody test and the rapid dengue NS1 antigen immunechromatographic test. The DENV-1 genome was detected with RT-PCR. Her 13-year old son, who had accompanied her, was also diagnosed as having dengue fever and he recovered without event. The Above-mentioned symptoms resolved within one week. However, the patient suffered from prolonged depression. She also noticed loss of hair 3 months after the disease onset Administration of a Serotonin-Noradrenalin Reuptake Inhibitor and a minor tranquillizer required to allow her requied to lead a normal life. Although she gradually felt better, it took approximately 2 years until she had recovered completely without taking any antidepressant and minor tranquillizer. It is a well-known fact in endemic countries that dengue fever could have an significant impact on the patients' mental well-being. However, it appears that physicians in non-endemic countries are not fully aware of the prolonged depression, which can occur subsequent to the acute illness. Follow-up consultations of returing travelers who have recoverd from dengu fever should be arranged to monitor their mental and emotional states closely.

  8. Luminescence properties of long-lasting phosphor SrMg2(PO4)2:Eu2+, Ho3+, Zr4+

    NASA Astrophysics Data System (ADS)

    Tang, Wei; Wang, Mingwen; Lin, Wei; Ye, Yaping; Wu, Xue

    2016-12-01

    Novel long lasting phosphors SrMg2(PO4)2:Eu2+, SrMg2(PO4)2:Eu2+, Zr4+, SrMg2(PO4)2:Eu2+, Ho3+ and SrMg2(PO4)2:Eu2+, Ho3+, Zr4+ were synthesized by conventional solid-state reaction method. The luminescent properties were systematically characterized by X-ray diffraction, photoluminescent excitation and emission spectra, as well as thermoluminescence spectrum and decay curves. The XRD patterns indicated that the samples belonged to monoclinic phase and co-doping Eu2+, Ho3+ and Zr4+ ions had no effect on the basic crystal structure. These phosphors emitting purplish blue light is related to the characteristic emission of Eu2+. The afterglow time of Eu2+ activated SrMg2(PO4)2 can be greatly enhanced by the co-doping of Ho3+, Zr4+. After the 365 nm UV light excitation source switching off, the Sr0.92Mg1.95(PO4)2:Eu2+0.01, Zr4+0.05, Ho3+0.07 phosphorescence can be observed for more than 1013 s in the limit of light perception of dark-adapted human eyes (0.32 mcd/m2). Different kinds of TL peaks at 423, 448 and 473 K have appeared, and traps densities have increased compared with the Eu2+ single doped SrMg2(PO4)2 phosphor. By analyzing the TL curve the depths of traps were calculated to be 0.846, 0.896 and 0.946 eV, respectively, which suggested that the co-doping of Ho3+, Zr4+ improved the electron storage ability of material. Besides, the mechanism was discussed in this report.

  9. Impact of long-lasting insecticidal nets on prevalence of subclinical malaria among children in the presence of pyrethroid resistance in Anopheles culicifacies in Central India.

    PubMed

    Chourasia, Mehul Kumar; Kamaraju, Raghavendra; Kleinschmidt, Immo; Bhatt, Rajendra M; Swain, Dipak Kumar; Knox, Tessa Bellamy; Valecha, Neena

    2017-04-01

    Subclinical (asymptomatic) cases of malaria could be a major barrier to the success of malaria elimination programs. This study has evaluated the impact of long-lasting insecticidal nets (LLINs) on the prevalence of subclinical malaria in the presence of pyrethroid resistance in the main malaria vector Anopheles culicifacies on malaria transmission among a cohort of children in villages of the Keshkal sub-district in Chhattisgarh state. A cohort of 6582 children ages less than 14 years was enrolled from 80 study clusters. Post monsoon survey was carried out at baseline before LLIN distribution, and 5862 children were followed up in the subsequent year. Study outcomes included assessment of subclinical malarial infections and use of LLINs among the study cohort in the presence of varied levels of pyrethroid resistance. In the baseline survey, the proportion of subclinical malaria was 6·1%. LLIN use during the previous night was 94·8%. Overall, prevalence of subclinical malaria was significantly reduced to 1% (p<0·001) in the second survey. LLIN users were protected from malaria (OR: 0·25, 95% CI=0·12-0·52, p<0.001) and subclinical malaria (OR: 0·25, 95% CI=0·11-0·58, p=0·001) despite the presence of pyrethroid resistance in the study area. In this low transmission area, sleeping under LLINs significantly reduced the burden of malaria among children. In the presence of pyrethroid resistant malaria vector, a high LLIN use of 94·5% was observed to have significantly brought down the proportion of subclinical malaria among the cohort children. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Long-lasting sensitization induced by repeated risperidone treatment in adolescent Sprague-Dawley rats: a possible D2 receptor mediated phenomenon?

    PubMed

    Qiao, Jing; Gao, Jun; Shu, Qing; Zhang, Qinglin; Hu, Gang; Li, Ming

    2014-04-01

    Risperidone use in children and adolescents for the treatment of various neuropsychiatric disorders (e.g., schizophrenia, autism, disruptive behavior, etc.) has increased substantially in recent decades. However, its long-term effect on the brain and behavioral functions is not well understood. The present study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response in adulthood in the conditioned avoidance response and phencyclidine (PCP)-induced hyperlocomotion tests. Male adolescent Sprague-Dawley rats (postnatal days [P] 40-44 or 43-48) were first treated with risperidone (0.3, 0.5, or 1.0 mg/kg, subcutaneously (sc)) and tested in the conditioned avoidance or PCP (3.2 mg/kg, sc)-induced hyperlocomotion model daily for five consecutive days. After they became adults (~P 76-80), they were challenged with risperidone (0.3 mg/kg, sc) to assess their sensitivity to risperidone reexposure. A quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test was later conducted to assess the risperidone-induced functional changes in D2 receptor. In the risperidone challenge test in adulthood, adult rats previously treated with risperidone in adolescence made significantly fewer avoidance responses and exhibited significantly lower PCP-induced hyperlocomotion than those previously treated with vehicle. They also appeared to be more hyperactive than the vehicle-pretreated ones in the quinpirole-induced hyperlocomotion test. Prepulse inhibition of acoustic startle or fear-induced 22 kHz ultrasonic vocalizations in adulthood was not altered by adolescence risperidone treatment. Adolescent risperidone exposure induces a long-term increase in behavioral sensitivity to risperidone that persists into adulthood. This long-lasting change might be due to functional upregulation of D2-mediated neurotransmission.

  11. Effectiveness of a new long-lasting insecticidal nets delivery model in two rural districts of Mozambique: a before-after study.

    PubMed

    Arroz, Jorge A H; Candrinho, Baltazar; Mendis, Chandana; Varela, Pablo; Pinto, João; Martins, Maria do Rosário O

    2018-02-05

    In 2015, Mozambique piloted a new model of long-lasting insecticidal nets (LLINs) delivery in a campaign. The new delivery model was used in two rural districts were, and two others were considered as control, maintaining the old delivery model. The aim of this study is to compare the coverage of ownership and use of LLINs in intervention and control districts in Mozambique. A before-after design with control group was carried out 6 months after LLINs distribution. Using systematic probabilistic sampling, 1547 households were surveyed by means of a questionnaire. To find associations between the district categories (intervention and control) and the main outcomes of the study (LLIN ownership, use, and universal coverage achievement), odds ratio (OR) and respective confidence intervals were calculated. Of the 760 households surveyed in the intervention districts, 98.8% had at least one LLIN; of the 787 households surveyed in the control districts, 89.6% had at least one LLIN [OR: 9.7, 95% (CI 4.84-19.46)]. Around 95 and 87% of households owning at least one LLIN reported having slept under the LLIN the previous night in the intervention and control districts, respectively [OR: 3.2; 95% (CI 2.12-4.69)]. Seventy-one percent of the households surveyed achieved universal coverage in the intervention districts against 59.6% in the control districts [OR: 1.6; 95% (CI 1.33-2.03)]. The universal coverage campaign piloted with the new delivery model has increased LLINs ownership, use, and progression for reaching universal coverage targets in the community.

  12. The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats.

    PubMed

    Yin, Qinqin; Li, Jun; Zheng, Qingshan; Yang, Xiaolin; Lv, Rong; Ma, Longxiang; Liu, Jin; Zhu, Tao; Zhang, Wensheng

    2017-01-01

    The quaternary lidocaine derivative (QX-314) in combination with bupivacaine can produce long-lasting nerve blocks in vivo, indicating potential clinical application. The aim of the study was to investigate the efficacy, safety, and the optimal formulation of this combination. QX-314 and bupivacaine at different concentration ratios were injected in the vicinity of the sciatic nerve in rats; bupivacaine and saline served as controls (n = 6~10). Rats were inspected for durations of effective sensory and motor nerve blocks, systemic adverse effects, and histological changes of local tissues. Mathematical models were established to reveal drug-interaction, concentration-effect relationships, and the optimal ratio of QX-314 to bupivacaine. 0.2~1.5% QX-314 with 0.03~0.5% bupivacaine produced 5.8~23.8 h of effective nerve block; while 0.5% bupivacaine alone was effective for 4 h. No systemic side effects were observed; local tissue reactions were similar to those caused by 0.5% bupivacaine if QX-314 were used < 1.2%. The weighted modification model was successfully established, which revealed that QX-314 was the main active ingredient while bupivacaine was the synergist. The formulation, 0.9% QX-314 plus 0.5% bupivacaine, resulted in 10.1 ± 0.8 h of effective sensory and motor nerve blocks. The combination of QX-314 and bupivacaine facilitated prolonged sciatic nerve block in rats with a satisfactory safety profile, maximizing the duration of nerve block without clinically important systemic and local tissue toxicity. It may emerge as an alternative approach to post-operative pain treatment.

  13. Locomotor exercise induces long-lasting impairments in the capacity of the human motor cortex to voluntarily activate knee extensor muscles.

    PubMed

    Sidhu, Simranjit K; Bentley, David J; Carroll, Timothy J

    2009-02-01

    Muscle fatigue is a reduction in the capacity to exert force and may involve a "central" component originating in the brain and/or spinal cord. Here we examined whether supraspinal factors contribute to impaired central drive after locomotor endurance exercise. On 2 separate days, 10 moderately active individuals completed a locomotor cycling exercise session or a control session. Brief (2 s) and sustained (30 s) isometric knee extension contractions were completed before and after locomotor exercise consisting of eight, 5-min bouts of cycling at 80% of maximum workload. In the control session, subjects completed the isometric contractions in a rested state. Twitch responses to supramaximal motor nerve stimulation and transcranial magnetic stimulation were obtained to assess peripheral force-generating capacity and voluntary activation. Maximum voluntary contraction (MVC) force during brief contractions decreased by 23 +/- 6.3% after cycling exercise and remained 12 +/- 2.8% below baseline 45 min later (F(1,9) > 15.5; P < 0.01). Resting twitch amplitudes declined by approximately 45% (F(1,9) = 28.3; P < 0.001). Cortical voluntary activation declined from 90.6 +/- 1.6% at baseline to 80.6 +/- 2.1% after exercise (F(1,9) = 28.0; P < 0.001) and remained significantly reduced relative to control 30-45 min later (80.6 +/- 3.4%; F(1,9) = 10.7; P < 0.01). Thus locomotor exercise caused a long-lasting impairment in the capacity of the motor cortex to drive the knee extensors. Force was reduced more during sustained MVC after locomotor exercise than in the control session. Peripheral mechanisms contributed relatively more to this force reduction in the control session, whereas supraspinal fatigue played a greater role in sustained MVC reduction after locomotor exercise.

  14. Long-Lasting Antidepressant Action of Ketamine, but Not Glycogen Synthase Kinase-3 Inhibitor SB216763, in the Chronic Mild Stress Model of Mice

    PubMed Central

    Jia, Min; Ma, Rui; Wang, Fen; Wu, Jin; Gao, Cheng-Ge; Hashimoto, Kenji

    2013-01-01

    Background Clinical studies demonstrate that the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that glycogen synthase kinase (GSK)-3 may underlie the rapid antidepressant action of ketamine, although the precise mechanisms are unclear. In this study, we examined the effects of ketamine and GSK-3 inhibitor SB216763 in the unpredictable, chronic mild stress (CMS) mouse model of mice. Methodology/Principal Findings Adult C57/B6 male mice were divided into 2 groups, a non-stressed control group and the unpredictable CMS (35 days) group. Then, either vehicle, ketamine (10 mg/kg), or the established GSK-3 inhibitor, SB216763 (10 mg/kg), were administered into mice in the CMS group, while vehicle was administered to controls. In the open field test, there was no difference between the four groups (control+vehicle, CMS+vehicle, CMS+ketamine, CMS+SB216763). In the sucrose intake test, a 1% sucrose intake drop, seen in CMS mice, was significantly attenuated after a single dose of ketamine, but not SB216763. In the tail suspension test (TST) and forced swimming test (FST), the increased immobility time seen in CMS mice was significantly attenuated by a single dose of ketamine, but not SB216763. Interestingly, the ketamine-induced increase in the sucrose intake test persisted for 8 days after a single dose of ketamine. Furthermore, a single administration of ketamine, but not SB216763, significantly attenuated the immobility time of the TST and FST in the control (non-stressed) mice. Conclusions/Significance These findings suggest that a single administration of ketamine, but not GSK-3 inhibitor SB216763, produces a long-lasting antidepressant action in CMS model mice. PMID:23390559

  15. Long-lasting distortion of GABA signaling in MS/DB neurons after binge-like ethanol exposure during initial synaptogenesis

    PubMed Central

    Wang, Haiying; DuBois, Dustin W.; Tobery, Angelika N.; Griffith, William H.; Brandt, Paul; Frye, Gerald D.

    2013-01-01

    Using a well-established model of binge-like ethanol treatment of rat pups on postnatal days (PD) 4–9, we found that maturation of GABAA receptor (GABAAR) miniature postsynaptic currents (mPSCs) was substantially blunted for medial septum/diagonal band (MS/DB) neurons in brain slices on PD 11–16. Ethanol reduced mPSC amplitude, frequency, and decay kinetics, while attenuating or exaggerating allosteric actions of zolpidem and allopregnanolone, respectively. The impact of ethanol in vivo was long lasting as most changes in MS/DB GABAAR mPSCs were still observed as late as PD 60–85. Maturing MS/DB neurons in naïve brain slices PD 4–16 showed increasing mPSC frequency, decay kinetics, and zolpidem sensitivity that were nearly identical to our earlier findings in cultured septal neurons [17, 18]. These rapidly developing mPSC parameters continued to mature through the first month of life then stabilized throughout the remainder of the lifespan. Finally, equivalent ethanol-induced alterations in GABAAR mPSC signaling were present in MS/DB neurons from both male and female animals. Previously, we showed ethanol treatment of cultured embryonic day 20 septal neurons distorts the maturation of GABAAR mPSCs predicting that early stages of GABAergic transmission in MS/DB neurons are vulnerable to intoxication injury [17, 18]. Since the overall character, timing, and magnitude of GABAergic mPSC developmental- and ethanol-induced changes in the in vivo model so closely mirror chronologically equivalent adaptations in cultured septal neurons, this suggests that such parallel models of ethanol impairment of GABAergic synaptic development in vivo and in vitro should be useful for translational studies exploring the efficacy and mechanism of action of potential therapeutic interventions from the cellular to whole animal level. PMID:23685190

  16. Plastic Jellyfish.

    ERIC Educational Resources Information Center

    Moseley, Christine

    2000-01-01

    Presents an environmental science activity designed to enhance students' awareness of the hazards of plastic waste for wildlife in aquatic environments. Discusses how students can take steps to reduce the effects of plastic waste. (WRM)

  17. Pilot study on the combination of an organophosphate-based insecticide paint and pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors in Burkina Faso.

    PubMed

    Mosqueira, Beatriz; Soma, Dieudonné D; Namountougou, Moussa; Poda, Serge; Diabaté, Abdoulaye; Ali, Ouari; Fournet, Florence; Baldet, Thierry; Carnevale, Pierre; Dabiré, Roch K; Mas-Coma, Santiago

    2015-08-01

    A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical

  18. Evaluation of a universal long-lasting insecticidal net (LLIN) distribution campaign in Ghana: cost effectiveness of distribution and hang-up activities

    PubMed Central

    2014-01-01

    Background Between May 2010 and October 2012, approximately 12.5 million long-lasting insecticidal nets (LLINs) were distributed through a national universal mass distribution campaign in Ghana. The campaign included pre-registration of persons and sleeping places, door-to-door distribution of LLINs with ‘hang-up’ activities by volunteers and post-distribution ‘keep-up’ behaviour change communication activities. Hang-up activities were included to encourage high and sustained use. Methods The cost and cost-effectiveness of the LLIN Campaign were evaluated using a before-after design in three regions: Brong Ahafo, Central and Western. The incremental cost effectiveness of the ‘hang-up’ component was estimated using reported variation in the implementation of hang-up activities and LLIN use. Economic costs were estimated from a societal perspective assuming LLINs would be replaced after three years, and included the time of unpaid volunteers and household contributions given to volunteers. Results Across the three regions, 3.6 million campaign LLINs were distributed, and 45.5% of households reported the LLINs received were hung-up by a volunteer. The financial cost of the campaign was USD 6.51 per LLIN delivered. The average annual economic cost was USD 2.90 per LLIN delivered and USD 6,619 per additional child death averted by the campaign. The cost-effectiveness of the campaign was sensitive to the price, lifespan and protective efficacy of LLINs. Hang-up activities constituted 7% of the annual economic cost, though the additional financial cost was modest given the use of volunteers. LLIN use was greater in households in which one or more campaign LLINs were hung by a volunteer (OR = 1.57; 95% CI = 1.09, 2.27; p = 0.02). The additional economic cost of the hang-up activities was USD 0.23 per LLIN delivered, and achieved a net saving per LLIN used and per death averted. Conclusion In this campaign, hang-up activities were estimated to be net

  19. The effect of repeated washing of long-lasting insecticide-treated nets (LLINs) on the feeding success and survival rates of Anopheles gambiae

    PubMed Central

    2010-01-01

    Background Insecticide-treated nets protect users from mosquito bites, thereby preventing transmissions of mosquito borne pathogens. Repeated washing of nets removes insecticide on the netting rendering them ineffective within a short period. Long-lasting insecticide-treated nets (LLINs) offer longer time protection against such bites because they are more wash resistant, and are preferred to conventionally treated nets. However, there is limited information on the effect of repeated washing of LLINs on the feeding success and survival of wild malaria vectors. Methods The current study evaluated the effect of repeated washing of four brands of LLINs on the feeding success and survival rates of Anopheles gambiae sl reared from wild strains. In this study, two- to five-day old F1s, reared from gravid mosquitoes collected from an area with a high coverage of LLINs were offered blood meals through protective barriers of the above LLINs. Mosquitoes were exposed for a period of 10 minutes each time. Nets were tested unwashed and subsequently after every 5th through wash 15. After exposure mosquitoes were sorted out according to their feeding status. They were then held under normal laboratory conditions for 24 hours and mortality was scored in both fed and unfed. Results It was observed that mosquitoes did not feed through a barrier of unwashed LLINs. However, the feeding success and survival rates increased with successive number of washes and were also net brand dependant. After 15 washes, 49% of vectors succeeded to feed through a protective barrier of PermaNet 2.0 and 50% of the fed died after 24 hrs while after the same number of washes 60% of vectors succeeded to feed through Olyset brand of LLINs and all of them survived. In general, more mosquitoes survived after feeding through Olyset compared to the other four brands that were evaluated. When efficacy of individual LLINs was compared by a t-test analysis to a conventionally treated net, the results were not

  20. Free mass distribution of long lasting insecticidal nets lead to high levels of LLIN access and use in Madagascar, 2010: A cross-sectional observational study.

    PubMed

    Finlay, Alyssa M; Butts, Jessica; Ranaivoharimina, Harilala; Cotte, Annett H; Ramarosandratana, Benjamin; Rabarijaona, Henintsoa; Tuseo, Luciano; Chang, Michelle; Vanden Eng, Jodi

    2017-01-01

    Madagascar conducted the first two phases of a national free mass distribution campaign of long-lasting insecticidal nets (LLINs) during a political crisis in 2009 aiming to achieve coverage of two LLINs per household as part of the National Malaria Control Strategy. The campaign targeted households in 19 out of 91 total health districts. A community-based cross-sectional household survey using a three-stage cluster sample design was conducted four months post campaign to assess LLIN ownership, access and use. Multivariable logistic regression analysis was used to identify factors associated with household LLIN access and individual LLIN use. A total of 2211 households were surveyed representing 8867 people. At least one LLIN was present in 93.5% (95% confidence interval [CI], 91.6-95.5%) of households and 74.8% (95% CI, 71.0-78.6%) owned at least two LLINs. Access measured as the proportion of the population that could potentially be covered by household-owned LLINs was 77.2% (77.2% (95% CI, 72.9-81.3%) and LLIN use by all individuals was 84.2% (95% CI, 81.2-87.2%). LLIN use was associated with knowledge of insecticide treated net use to prevent malaria (OR = 3.58, 95% CI, 1.85-6.94), household ownership of more LLINs (OR 2.82, 95% CI 1.85-4.3), presence of children under five (OR = 2.05, 95% CI, 1.67-2.51), having traveled to the distribution point and receiving information about hanging a bednet (OR = 1.56, 95% CI, 1.41-1.74), and having received a post-campaign visit by a community mobilizer (OR = 1.75, 95% CI, 1.26-2.43). Lower LLIN use was associated with increasing household size (OR = 0.81 95% CI 0.77-0.85) and number of sleeping spaces (OR = 0.55, 95% CI, 0.44-0.68). A large scale free mass LLIN distribution campaign was feasible and effective at achieving high LLIN access and use in Madagascar. Campaign process indicators highlighted potential areas for strengthening implementation to optimize access and equity.

  1. Free mass distribution of long lasting insecticidal nets lead to high levels of LLIN access and use in Madagascar, 2010: A cross-sectional observational study

    PubMed Central

    Butts, Jessica; Ranaivoharimina, Harilala; Cotte, Annett H.; Ramarosandratana, Benjamin; Rabarijaona, Henintsoa; Tuseo, Luciano; Chang, Michelle; Vanden Eng, Jodi

    2017-01-01

    Background Madagascar conducted the first two phases of a national free mass distribution campaign of long-lasting insecticidal nets (LLINs) during a political crisis in 2009 aiming to achieve coverage of two LLINs per household as part of the National Malaria Control Strategy. The campaign targeted households in 19 out of 91 total health districts. Methods A community-based cross-sectional household survey using a three-stage cluster sample design was conducted four months post campaign to assess LLIN ownership, access and use. Multivariable logistic regression analysis was used to identify factors associated with household LLIN access and individual LLIN use. Results A total of 2211 households were surveyed representing 8867 people. At least one LLIN was present in 93.5% (95% confidence interval [CI], 91.6–95.5%) of households and 74.8% (95% CI, 71.0–78.6%) owned at least two LLINs. Access measured as the proportion of the population that could potentially be covered by household-owned LLINs was 77.2% (77.2% (95% CI, 72.9–81.3%) and LLIN use by all individuals was 84.2% (95% CI, 81.2–87.2%). LLIN use was associated with knowledge of insecticide treated net use to prevent malaria (OR = 3.58, 95% CI, 1.85–6.94), household ownership of more LLINs (OR 2.82, 95% CI 1.85–4.3), presence of children under five (OR = 2.05, 95% CI, 1.67–2.51), having traveled to the distribution point and receiving information about hanging a bednet (OR = 1.56, 95% CI, 1.41–1.74), and having received a post-campaign visit by a community mobilizer (OR = 1.75, 95% CI, 1.26–2.43). Lower LLIN use was associated with increasing household size (OR = 0.81 95% CI 0.77–0.85) and number of sleeping spaces (OR = 0.55, 95% CI, 0.44–0.68). Conclusions A large scale free mass LLIN distribution campaign was feasible and effective at achieving high LLIN access and use in Madagascar. Campaign process indicators highlighted potential areas for strengthening implementation to optimize

  2. "We are supposed to take care of it": a qualitative examination of care and repair behaviour of long-lasting, insecticide-treated nets in Nasarawa State, Nigeria.

    PubMed

    Hunter, Gabrielle C; Scandurra, Leah; Acosta, Angela; Koenker, Hannah; Obi, Emmanuel; Weber, Rachel

    2014-08-14

    The longevity of long-lasting insecticidal nets (LLIN) under field conditions has important implications for malaria vector control. The behaviour of bed net users, including net care and repair, may protect or damage bed nets and impact the physical integrity of nets. However, this behaviour, and the motivating and inhibiting factors, is not well understood. Qualitative research methods were used to examine behaviour, attitudes and norms around damage, care and repair of LLINs. Eighteen in-depth interviews (IDI) and six focus group discussions (FGD) were conducted with LLIN users in two local government areas of Nasarawa State, Nigeria. A brief background questionnaire with the 73 participants prior to IDIs or FGDs collected additional data on demographics, net use, and care and repair behaviour. Respondents cited that the major causes of damage to bed nets are primarily children, followed by rodents, everyday handling that is not gentle, and characteristics of sleeping spaces. Caring for nets was perceived as both preventing damage by careful handling and keeping the net clean, which may lead to over-washing of LLINs. Repairing a damaged net was considered something that net users should do and the responsibility of adults in the household. Despite this, reported frequency of net repair was low (18%). Motivations for taking care of and repairing nets centred around caring for one's family, avoiding mosquito bites, saving money, and maintaining the positive opinion of others by keeping a clean and intact net. Barriers to net care and repair related to time availability and low perceived value of bed nets or of one's health. This study provides novel and valuable insights on the perceptions and attitudes of LLIN users in Nasarawa, Nigeria on the durability of bed nets, how to care for and repair nets, and for what reasons. Communication around net care should stress proper daily storage of nets, regular net inspections, prompt repairs, and clarify misconceptions

  3. A stitch in time: a cross-sectional survey looking at long lasting insecticide-treated bed net ownership, utilization and attrition in SNNPR, Ethiopia

    PubMed Central

    2012-01-01

    Background Since 2002/03, an estimated 4.7 million nets have been distributed in the Southern Nations, Nationalities and Peoples Region (SNNPR) among an at risk population of approximately 10 million people. Evidence from the region suggests that large-scale net ownership rapidly increased over a relatively short period of time. However, little is known about how coverage is being maintained given that the last mass distribution was in 2006/2007. This study sought to determine the status of current net ownership, utilization and rate of long lasting insecticide-treated nets (LLIN) loss in the previous three years in the context of planning for future net distribution to try to achieve sustainable universal coverage. Methods A total of 750 household respondents were interviewed across malarious, rural kebeles of SNNPR. Households were randomly selected following a two-stage cluster sampling design where kebeles were defined as clusters. Kebeles were chosen using proportional population sampling (PPS), and 25 households within 30 kebeles randomly chosen. Results Approximately 67.5% (95%CI: 64.1–70.8) of households currently owned at least one net. An estimated 31.0% (95%CI 27.9–34.4) of all nets owned in the previous three years had been discarded by owners, the majority of whom considered the nets too torn, old or dirty (79.9%: 95%CI 75.8–84.0). Households reported that one-third of nets (33.7%) were less than one year old when they were discarded. The majority (58.8%) of currently owned nets had ‘good’ structural integrity according to a proportionate Hole Index. Nearly two-thirds of households (60.6%) reported using their nets the previous night. The overriding reason for not using nets was that they were too torn (45.7%, 95% CI 39.1–50.7). Yet, few households are making repairs to their nets (3.7%, 95% CI: 2.4–5.1). Conclusions Results suggest that the life span of nets may be shorter than previously thought, with little maintenance by their owners

  4. Traditional Nets Interfere with the Uptake of Long-Lasting Insecticidal Nets in the Peruvian Amazon: The Relevance of Net Preference for Achieving High Coverage and Use

    PubMed Central

    Grietens, Koen Peeters; Muela Ribera, Joan; Soto, Veronica; Tenorio, Alex; Hoibak, Sarah; Aguirre, Angel Rosas; Toomer, Elizabeth; Rodriguez, Hugo; Llanos Cuentas, Alejandro; D'Alessandro, Umberto; Gamboa, Dionicia; Erhart, Annette

    2013-01-01

    Background While coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset® LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru. Methods The study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses). Results A total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset® LLINs ultimately did not. The LLINs' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], p<0.001). Conclusion Net preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent

  5. Design, implementation and evaluation of a national campaign to deliver 18 million free long-lasting insecticidal nets to uncovered sleeping spaces in Tanzania

    PubMed Central

    2013-01-01

    Background Since 2004, the Tanzanian National Voucher Scheme has increased availability and accessibility of insecticide-treated nets (ITNs) to pregnant women and infants by subsidizing the cost of nets purchased. From 2008 to 2010, a mass distribution campaign delivered nine million long-lasting insecticidal nets (LLINs) free-of-charge to children under-five years of age in Tanzania mainland. In 2010 and 2011, a Universal Coverage Campaign (UCC) led by the Ministry of Health and Social Welfare (MoHSW) was implemented to cover all sleeping spaces not yet reached through previous initiatives. Methods The UCC was coordinated through a unit within the National Malaria Control Programme. Partners were contracted by the MoHSW to implement different activities in collaboration with local government authorities. Volunteers registered the number of uncovered sleeping spaces in every household in the country. On this basis, LLINs were ordered and delivered to village level, where they were issued over a three-day period in each zone (three regions). Household surveys were conducted in seven districts immediately after the campaign to assess net ownership and use. Results The UCC was chiefly financed by the Global Fund to Fight AIDS, Tuberculosis and Malaria with important contributions from the US President’s Malaria Initiative. A total of 18.2 million LLINs were delivered at an average cost of USD 5.30 per LLIN. Overall, 83% of the expenses were used for LLIN procurement and delivery and 17% for campaign associated activities. Preliminary results of the latest Tanzania HIV Malaria Indicator Survey (2011–12) show that household ownership of at least one ITN increased to 91.5%. ITN use, among children under-five years of age, improved to 72.7% after the campaign. ITN ownership and use data post-campaign indicated high equity across wealth quintiles. Conclusion Close collaboration among the MoHSW, donors, contracted partners, local government authorities and volunteers

  6. Long-Lasting Increased Risk of Human Papillomavirus-Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study.

    PubMed

    Ebisch, Renée M F; Rutten, Dominiek W E; IntHout, Joanna; Melchers, Willem J G; Massuger, Leon F A G; Bulten, Johan; Bekkers, Ruud L M; Siebers, Albert G

    2017-08-01

    Purpose The aim of this study was to determine the risk of human papillomavirus (HPV)-related carcinomas and premalignancies in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3). Knowledge of this risk is important to preventing the development and progression of other HPV-related premalignancies and carcinomas, by considering prophylactic HPV vaccination and/or by paying increased attention to other HPV-related carcinomas and premalignancies when CIN3 is identified. Methods Women diagnosed with a CIN3 between 1990 and 2010 were identified from the Dutch nationwide registry of histopathology and cytopathology (PALGA) and matched with a control group of women without CIN3. Subsequently, all cases of high-risk (hr) HPV-associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015 were extracted. Incidence rate ratios were estimated for carcinomas and premalignancies of the vulva, vagina, anus, and oropharynx. Results A total of 178,036 women were identified: 89,018 with a previous diagnosis of CIN3 and 89,018 matched control subjects without a history of CIN3. Women with a history of CIN3 showed increased risk of HPV-related carcinomas and premalignancies, with incidence rate ratios of 3.85 (95% CI, 2.32 to 6.37) for anal cancer, 6.68 (95% CI, 3.64 to 12.25) for anal intraepithelial neoplasia grade 3, 4.97 (95% CI, 3.26 to 7.57) for vulvar cancer, 13.66 (93% CI, 9.69 to 19.25) for vulvar intraepithelial neoplasia grade 3, 86.08 (95% CI, 11.98 to 618.08) for vaginal cancer, 25.65 (95% CI, 10.50 to 62.69) for vaginal intraepithelial neoplasia grade 3, and 5.51 (95% CI, 1.22 to 24.84) for oropharyngeal cancer. This risk remained significantly increased, even after long-term follow-up of up to 20 years. Conclusion This population-based study shows a long-lasting increased risk for HPV-related carcinomas and premalignancies of the anogenital and oropharyngeal region after a CIN3 diagnosis. Studies that

  7. Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates

    PubMed Central

    Rigato, Paula Ordonhez; Maciel, Milton; Goldoni, Adriana Letícia; Piubelli, Orlando Guerra; Orii, Noemia Mie; Marques, Ernesto Torres; August, Joseph Thomas; Duarte, Alberto José da Silva; Sato, Maria Notomi

    2012-01-01

    Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-γ-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods. PMID:22355381

  8. Cost-effectiveness analysis of vaccinating children in Malawi with RTS,S vaccines in comparison with long-lasting insecticide-treated nets.

    PubMed

    Seo, Mikyung Kelly; Baker, Peter; Ngo, Karen Ngoc-Lan

    2014-02-24

    New RTS,S malaria vaccines may soon be licensed, yet its cost-effectiveness is unknown. Before the widespread introduction of RTS,S vaccines, cost-effectiveness studies are needed to help inform governments in resource-poor settings about how best to prioritize between the new vaccine and existing malaria interventions. A Markov model simulated malaria progression in a hypothetical Malawian birth cohort. Parameters were based on published data. Three strategies were compared: no intervention, vaccination at one year, and long-lasting, insecticide-treated nets (LLINs) at birth. Both health service and societal perspectives were explored. Health outcomes were measured in disability-adjusted life years (DALYs) averted and costed in 2012 US$. Incremental cost-effectiveness ratios (ICERs) were calculated and extensive sensitivity analyses were conducted. Three times GDP per capita ($1,095) per DALY averted was used for a cost-effectiveness threshold, whilst one times GDP ($365) was considered 'very cost-effective'. From a societal perspective the vaccine strategy was dominant. It averted 0.11 more DALYs than LLINs and 0.372 more DALYs than the no intervention strategy per person, while costing $10.04 less than LLINs and $59.74 less than no intervention. From a health service perspective the vaccine's ICER was $145.03 per DALY averted, and thus can be considered very cost-effective. The results were robust to changes in all variables except the vaccine and LLINs' duration of efficacy. Vaccines remained cost-effective even at the lowest assumed efficacy levels of 49.6% (mild malaria) and 14.2% (severe malaria), and the highest price of $15. However, from a societal perspective, if the vaccine duration efficacy was set below 2.69 years or the LLIN duration of efficacy was greater than 4.24 years then LLINs became the more cost-effective strategy. The results showed that vaccinating Malawian children with RTS,S vaccines was very cost-effective from both a societal and a

  9. Cost-effectiveness analysis of vaccinating children in Malawi with RTS,S vaccines in comparison with long-lasting insecticide-treated nets

    PubMed Central

    2014-01-01

    Background New RTS,S malaria vaccines may soon be licensed, yet its cost-effectiveness is unknown. Before the widespread introduction of RTS,S vaccines, cost-effectiveness studies are needed to help inform governments in resource-poor settings about how best to prioritize between the new vaccine and existing malaria interventions. Methods A Markov model simulated malaria progression in a hypothetical Malawian birth cohort. Parameters were based on published data. Three strategies were compared: no intervention, vaccination at one year, and long-lasting, insecticide-treated nets (LLINs) at birth. Both health service and societal perspectives were explored. Health outcomes were measured in disability-adjusted life years (DALYs) averted and costed in 2012 US$. Incremental cost-effectiveness ratios (ICERs) were calculated and extensive sensitivity analyses were conducted. Three times GDP per capita ($1,095) per DALY averted was used for a cost-effectiveness threshold, whilst one times GDP ($365) was considered ‘very cost-effective’. Results From a societal perspective the vaccine strategy was dominant. It averted 0.11 more DALYs than LLINs and 0.372 more DALYs than the no intervention strategy per person, while costing $10.04 less than LLINs and $59.74 less than no intervention. From a health service perspective the vaccine’s ICER was $145.03 per DALY averted, and thus can be considered very cost-effective. The results were robust to changes in all variables except the vaccine and LLINs’ duration of efficacy. Vaccines remained cost-effective even at the lowest assumed efficacy levels of 49.6% (mild malaria) and 14.2% (severe malaria), and the highest price of $15. However, from a societal perspective, if the vaccine duration efficacy was set below 2.69 years or the LLIN duration of efficacy was greater than 4.24 years then LLINs became the more cost-effective strategy. Conclusion The results showed that vaccinating Malawian children with RTS,S vaccines was

  10. A village level cluster-randomized entomological evaluation of combination long-lasting insecticidal nets containing pyrethroid plus PBO synergist in Southern Mali.

    PubMed

    Cisse, Moussa B M; Sangare, Djibril; Oxborough, Richard M; Dicko, Abdourhamane; Dengela, Dereje; Sadou, Aboubacar; Mihigo, Jules; George, Kristen; Norris, Laura; Fornadel, Christen

    2017-11-21

    There is growing concern that malaria vector resistance to pyrethroid insecticides may reduce the effectiveness of long-lasting insecticidal nets (LLINs). Combination LLINs are designed to control susceptible and pyrethroid-resistant mosquito populations through a mixture of pyrethroid with piperonyl butoxide (PBO) synergist. A cluster randomized trial with entomology outcome measures was conducted in Mali to determine the added benefit over mono-treated pyrethroid predecessors. Four LLIN treatments; permethrin + PBO, permethrin, deltamethrin + PBO, and deltamethrin, were randomly allocated to four villages each (16 villages total) and distributed to cover every sleeping place. Entomological monitoring of indoor Anopheles resting densities, host preference, vector longevity, and sporozoite rates were monitored every 2 months over 2 years in 2014 and 2015. Bottle bioassays confirmed permethrin and deltamethrin resistance in Anopheles gambiae sensu lato (s.l.), (the predominant species throughout the study) with pre-exposure to PBO indicating partial involvement of oxidases. Between 2014 and 2015 the mean indoor resting density was greater in the deltamethrin + PBO LLIN arm than the deltamethrin LLIN arm at 3.05 (95% CI 3.00-3.10) An. gambiae s.l. per room per day compared with 1.9 (95% CI 1.87-1.97). There was no significant difference in sporozoite rate at 3.97% (95% CI 2.91-5.02) for the deltamethrin LLIN arm and 3.04% (95% CI 2.21-3.87) for deltamethrin + PBO LLIN arm (P = 0.17). However, when analysed by season there was some evidence that the sporozoite rate was lower in the deltamethrin + PBO LLIN arm than deltamethrin LLIN arm during the rainy/high malaria transmission seasons at 1.95% (95% CI 1.18-2.72) and 3.70% (95% CI 2.56-4.84) respectively (P = 0.01). While there was some evidence that An. gambiae s.l. sporozoite rates were lower in villages with deltamethrin + PBO LLINs during the high malaria transmission seasons of 2014-2015, there

  11. The effect of household heads training on long-lasting insecticide-treated bed nets utilization: a cluster randomized controlled trial in Ethiopia.

    PubMed

    Deribew, Amare; Birhanu, Zewdie; Sena, Lelisa; Dejene, Tariku; Reda, Ayalu A; Sudhakar, Morankar; Alemseged, Fessehaye; Tessema, Fasil; Zeynudin, Ahmed; Biadgilign, Sibhatu; Deribe, Kebede

    2012-03-30

    Long-lasting insecticide-treated bed nets (LLITN) have demonstrated significant impact in reducing malaria-related childhood morbidity and mortality. However, utilization of LLITN by under-five children is not satisfactory in many sub-Saharan African countries due to behavioural barriers. Previous studies had focused on the coverage and ownership of LLITN. The effect of skill-based training for household heads on LLITN utilization had not yet been investigated. A cluster-randomized trial on the effect of training of household heads on the use of LLITN was done in Ethiopia to fill this knowledge gap. The study included 22 (11 intervention and 11 control) villages in southwest Ethiopia. The intervention consisted of tailored training of household heads about the proper use of LLITN and community network system. All households in each group received free LLITN. Data were collected at baseline, six and 12 months of the follow up periods. Utilization of LLITN in the control and intervention villages was compared at baseline and follow up periods. A total of 21,673; 14,735 and 13,758 individuals were included at baseline, sixth and twelfth months of the project period. At the baseline survey, 47.9% of individuals in the intervention villages and 68.4% in the control villages reported that they had utilized LLITN the night before the survey. At the six month, 81.0% of individuals in the intervention villages and 79.3% in the control villages had utilized LLITN. The utilization of LLITN in all age groups in the intervention villages was increased by 17.7 percentage point (95% CI 9.7-25.6) at sixth month and by 31.0 percentage point (95% CI 16.9-45.1) at the twelfth month. Among under-five children, the LLITN utilization increased by 31.6 percentage point (95% CI 17.3-45.8) at the sixth month and 38.4 percentage point (95% CI 12.1-64.7) at the twelfth months of the project period. Household level skill-based training has demonstrated a marked positive effect in the

  12. Interceptor® long-lasting insecticidal net: phase III evaluation over three years of household use and calibration with Phase II experimental hut outcomes.

    PubMed

    Tungu, Patrick; Kirby, Matthew; Malima, Robert; Kisinza, William; Magesa, Stephen; Maxwell, Caroline; Batengana, Benard; Pigeon, Olivier; Rowland, Mark

    2016-04-13

    Long-lasting insecticidal nets (LN) are an effective tool for malaria prevention. The World Health Organization Pesticide Evaluation Scheme has established evaluation criteria to facilitate registration for public use. A household randomised trial was conducted in Tanzania according to WHOPES Phase III procedures to evaluate the alpha-cypermethrin coated Interceptor® LN (BASF) over three years' use. Outcomes were calibrated against results of Phase II experimental hut trials. Interceptor LN (200 mg/m(2) alpha-cypermethrin) and conventionally treated nets CTN (40 mg/m(2) alpha-cypermethrin) were randomly distributed to 934 households. At 6-monthly intervals, household surveys recorded net use, durability, adverse effects, user acceptance and washing practices. Concurrently, 30 nets of each type were collected and tested for knock-down and kill of Anopheles gambiae mosquitoes in cone and tunnel bioassays. Alpha-cypermethrin content of nets was assessed annually. At 12 months 97% of Interceptor LN met the efficacy criteria by cone or tunnel test; this pass rate declined to 90% at 24 months and 87% at 36 months. In contrast only 63% of CTN met the efficacy criteria at 12 months, 14 % at 24 months and 0% at 36 months. The alpha-cypermethrin content at 36 months on Interceptor LN was 20% (42 ± 13 mg/m(2)) of the initial content but on CTNs only 4% (1.3 ± 1.6 mg/m(2)) remained. Interceptor LN was reported to be used year-round and washed 4.3 times/year. A few recalled facial tingling during the first days of use but this did not deter usage. The average number of holes at 36 months was 18, hole area per net was 229 cm(2) and hole index was 332. Insecticide content and cone bioefficacy of LN and CTN after 36 months' use were similar to that of LN and CTN used in earlier Phase II hut trials, but while the 20 times washed LN tested in experimental huts gave adequate personal protection the 20 times washed CTN did not. More than 80% Interceptor LN fulfilled the

  13. Long-lasting insecticidal net source, ownership and use in the context of universal coverage: a household survey in eastern Rwanda.

    PubMed

    Kateera, Fredrick; Ingabire, Chantal M; Hakizimana, Emmanuel; Rulisa, Alexis; Karinda, Parfait; Grobusch, Martin P; Mutesa, Leon; van Vugt, Michèle; Mens, Petra F

    2015-10-06

    Universal long-lasting insecticidal net (LLIN) coverage (ULC) has reduced malaria morbidity and mortality across Africa. Although information is available on bed net use in specific groups, such as pregnant women and children under 5 years, there is paucity of data on their use among the general population. Bed net source, ownership and determinants of use among individuals from households in an eastern Rwanda community 8 months after a ULC were characterized. Using household-based, interviewer-administered questionnaires and interviewer-direct observations, data on bed net source, ownership and key determinants of net use, including demographics, socio-economic status indicators, house structure characteristics, as well as of bed net quantity, type and integrity, were collected from 1400 randomly selected households. Univariate and mixed effects logistic regression modelling was done to assess for determinants of bed net use. A total of 1410 households and 6598 individuals were included in the study. Overall, the proportion of households with at least one net was 92 % while bed net usage was reported among 72 % of household members. Of the households surveyed, a total ownership of 2768 nets was reported, of which about 96 % were reportedly LLINs received from the ULC. By interviewer-physical observation, 88 % of the nets owned were of the LLIN type with the remaining 12 % did not carry any mark to enable type recognition. The odds of bed net use were significantly lower among males and individuals: from households of low socio-economic status, from households with

  14. Field durability of the same type of long-lasting insecticidal net varies between regions in Nigeria due to differences in household behaviour and living conditions.

    PubMed

    Kilian, Albert; Koenker, Hannah; Obi, Emmanuel; Selby, Richmond A; Fotheringham, Megan; Lynch, Matthew

    2015-03-24

    With the recent publication of WHO-recommended methods to estimate net survival, comparative analyses from different areas have now become possible. With this in mind, a study was undertaken in Nigeria to compare the performance of a specific long-lasting insecticidal net (LLIN) product in three socio-ecologically different areas. In addition, the objective was to assess the feasibility of a retrospective study design for durability. In three states, Zamfara in the north, Nasarawa in the centre and Cross River in the south, four local government areas were selected one year after mass distribution of 100-denier polyester LLINs. From a representative sample of 300 households per site that had received campaign nets, an assessment of net survival was made based on rate of loss of nets and the physical condition of surviving nets measured by the proportionate hole index (pHI). Surveys were repeated after two and three years. Over the three-year period 98% of the targeted sample size of 3,720 households was obtained and 94% of the 5,669 campaign nets found were assessed for damage. With increasing time since distribution, recall of having received campaign nets dropped by 11-22% and only 31-87% of nets actually lost were reported. Using a recall bias adjustment, attrition rates were fairly similar in all three sites. The proportion of surviving nets in serviceable condition differed dramatically, however, resulting in an estimated median net survival of 3.0 years in Nasarawa, 4.5 years in Cross River and 4.7 years in Zamfara. Although repairs on damaged nets increased from around 10% at baseline to 21-38% after three years, the average pHI value for each of the four hole size categories did not differ between repaired and unrepaired nets. First, the differences observed in net survival are driven by living conditions and household behaviours and not the LLIN material. Second, recall bias in a retrospective durability study can be significant and while adjustments can

  15. Repeated mass distributions and continuous distribution of long-lasting insecticidal nets: modelling sustainability of health benefits from mosquito nets, depending on case management

    PubMed Central

    2013-01-01

    Background Stagnating funds for malaria control have spurred interest in the question of how to sustain the gains of recent successes with long-lasting insecticidal nets (LLINs) and improved case management (CM). This simulation study examined the malaria transmission and disease dynamics in scenarios with sustained LLINs and CM interventions and tried to determine optimal LLIN distribution rates. The effects of abruptly halting LLIN distribution were also examined. Methods Dynamic simulations of malaria in humans and mosquitoes were run on the OpenMalaria platform, using stochastic individual-based simulation models. LLINs were distributed in a range of transmission settings, with varying CM coverage levels. Results In the short-term, LLINs were beneficial over the entire transmission spectrum, reducing both transmission and disease burden. In the long-term, repeated distributions sustainably reduced transmission in all settings. However, because of the resulting reduction in acquired immunity in the population, the malaria disease burden, after initially being reduced, gradually increased and eventually stabilized at a new level. This new level was higher than the pre-intervention level in previously high transmission settings, if there is a maximum disease burden in the relationship between transmission and disease burden at intermediate transmission levels. This result could lead one to conclude that sustained LLIN distribution might not be cost-effective in high transmission settings in the long term. However, improved CM rendered LLINs more cost-effective in higher transmission settings than in those without improved CM and the majority of the African population lives in areas where CM and LLINs are sustainably combined. The effects of changes in LLIN distribution rate on cost-effectiveness were relatively small compared to the effects of changes in transmission setting and CM. Abruptly halting LLIN distribution led to temporary morbidity peaks, which were

  16. Challenges and opportunities associated with the introduction of next-generation long-lasting insecticidal nets for malaria control: a case study from Burkina Faso.

    PubMed

    Tesfazghi, Kemi; Traore, Adama; Ranson, Hilary; N'Fale, Sagnon; Hill, Jenny; Worrall, Eve

    2016-07-22

    Reductions in malaria incidence in Africa can largely be attributed to increases in malaria vector control activities; predominately the use of long-lasting insecticidal nets (LLINs). With insecticide resistance affecting an increasing number of malaria-endemic countries and threatening the effectiveness of conventional LLINs, there is an increasing urgency to implement alternative tools that control these resistant populations. The aim of this study was to identify potential challenges and opportunities for accelerating access to next-generation LLINs in Burkina Faso, a country with areas of high levels of insecticide resistance. An analytical framework was used to guide the selection of interviewees, data collection and analysis. Semi-structured interviews were carried out with key informants in April 2014 in Burkina Faso. Interviews were conducted in French and English, audio recorded, transcribed and entered into NVivo 10 for data management and analysis. Data were coded according to the framework themes and then analysed to provide a description of the key points and explain patterns in the data. Interviewees reported that the policy architecture in Burkina Faso is characterised by a strong framework of actors that contribute to policymaking and strong national research capacity which indirectly contributes to national policy change via collaboration with internationally led research. Financing significantly impacts the potential adoption, availability and affordability of next-generation LLINs. This confers significant power on international donors that fund vector control. National decisions around which LLINs to procure were restricted to quantity and delivery dates; the potential to tackle insecticide resistance was not part of the decision-making process. Furthermore, at the time of the study, there was no World Health Organization (WHO) guidance on where and when next-generation LLINs might positively impact on malaria transmission, severely limiting

  17. Bioefficacy of long-lasting insecticidal nets against pyrethroid-resistant populations of Anopheles gambiae s.s. from different malaria transmission zones in Uganda

    PubMed Central

    2013-01-01

    Background There are major concerns over sustaining the efficacy of current malaria vector control interventions given the rapid spread of resistance, particularly to pyrethroids. This study assessed the bioefficacy of five WHO-recommended long-lasting insecticidal nets (LLINs) against pyrethroid-resistant Anopheles gambiae field populations from Uganda. Methods Adult An. gambiae from Lira, Tororo, Wakiso and Kanungu districts were exposed to permethrin (0.75%) or deltamethrin (0.05%) in standard WHO susceptibility tests. Cone bioassays were used to measure the bioefficacy of four mono-treated LLINs (Olyset®, Interceptor®, Netprotect® and PermaNet® 2.0) and one combination LLIN (PermaNet® 3.0) against the four mosquito populations. Wireball assays were similarly conducted to determine knockdown rates. Species composition and kdr mutation frequency were determined for a sample of mosquitoes from each population. Chemical assays confirmed that test nets fell within target dose ranges. Results Anopheles gambiae s.s. predominated at all four sites (86 - 99% of Anopheles spp.) with moderate kdr L1014S allelic frequency (0.34 – 0.37). Confirmed or possible resistance to both permethrin and deltamethrin was identified for all four test populations. Reduced susceptibility to standard LLINs was observed for all four populations, with mortality rates as low as 45.8% even though the nets were unused. The combination LLIN PermaNet®3.0 showed the highest overall bioefficacy against all four An. gambiae s.l. populations (98.5 - 100% mortality). Wireball assays provided a more sensitive indicator of comparative bioefficacy, and PermaNet 3.0 was again associated with the highest bioefficacy against all four populations (76.5 – 91.7% mortality after 30 mins). Conclusions The bioefficacy of mono-treated LLINs against pyrethroid-resistant field populations of An. gambiae varied by LLIN type and mosquito population, indicating that certain LLINs may be more suitable than

  18. Protein Phosphatase 1-Dependent Transcriptional Programs for Long-Term Memory and Plasticity

    ERIC Educational Resources Information Center

    Graff, Johannes; Koshibu, Kyoko; Jouvenceau, Anne; Dutar, Patrick; Mansuy, Isabelle M.

    2010-01-01

    Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and…

  19. Activin induces long-lasting N-methyl-D-aspartate receptor activation via scaffolding PDZ protein activin receptor interacting protein 1.

    PubMed

    Kurisaki, A; Inoue, I; Kurisaki, K; Yamakawa, N; Tsuchida, K; Sugino, H

    2008-02-19

    Calcium entry into the postsynaptic neuron through N-methyl-D-aspartate-type glutamate receptors (NMDARs) triggers the induction of long-term potentiation (LTP), which is considered to contribute to synaptic plasticity and plays a critical role in behavioral learning. We report here that activin, a member of the transforming growth factor-beta (TGF-beta) superfamily, promotes phosphorylation of NMDARs and increases the Ca2+ influx through these receptors in primary cultured rat hippocampal neurons. This signal transduction occurs in a functional complex of activin receptors, NMDARs, and Src family tyrosine kinases, including Fyn, formed on a multimer of postsynaptic scaffolding postsynaptic density protein 95/Dlg/ZO-1 (PDZ), activin receptor interacting protein 1 (ARIP1). Activin-induced NMDAR activation persists for more than 24 h, which is complimentary to the activation time of NMDARs by brain-derived neurotrophic factor (BDNF). Our results suggest that activin is a unique and powerful potentiator for NMDAR-dependent signaling, which could be involved in the regulatory mechanisms of synaptic plasticity.

  20. Synergistic insecticidal and repellent effects of combined pyrethroid and repellent-impregnated bed nets using a novel long-lasting polymer-coating multi-layer technique.

    PubMed

    Faulde, Michael K; Nehring, Oliver

    2012-08-01

    New and improved strategies for malaria control and prevention are urgently needed. As a contribution to an optimized personal protection strategy, a novel long-lasting insecticide and repellent-treated net (LLIRN) has been designed by binding combinations of permethrin plus N,N-diethyl-m-toluamide (DEET), or insect repellent 3535 (IR3535), and etofenprox plus DEET, onto fibres of bed net fabric employing a new multi-layer polymer-coating technique. Protective repellent efficacy, toxicological effectiveness and residual activity of 12 LLIRN types have been evaluated by laboratory testing against adult Aedes aegypti. The novel multi-layer LLIRN design allowed simultaneous embedding at concentrations up to 5,930 mg/m(2) for DEET, 3,408 mg/m(2) for IR3535, 2,296 mg/m(2) for permethrin and 2,349 mg/m(2) for etofenprox, respectively. IR3535 layers prevented co-binding of additional pyrethroid-containing polymer layers, thus making pyrethroids plus DEET LLIRNs an ideal combination. All LLIRNs revealed synergistic insecticidal effects which, when measured against concentration controls of the isolated compounds, were significant in all LLIRN types designed. DEET in DEET plus permethrin LLIRNs significantly (p < 0.0001) reduced the concentration-dependent permethrin 100 % knockdown (KD) time from 55 to 75 %, the corresponding 100 % kill time (p < 0.0001) from 55 to 64 %. DEET in DEET plus etofenprox LLIRNs reduced the dose-specific 100 % knockdown (KD) time of etofenprox from 42 to 50 % (p = 0.004), the 100 % kill time from 25 to 38 % (p < 0.0001). Permethrin or etofenprox did not influence spatial repellency of DEET or IR3535 on LLIRNs. Vice versa, DEET and IR3535 increased spatial and excitatory repellency and reduced landing and probing frequency on LLIRNs resulting in strongly enhanced biting protection, even at low concentrations. One hundred percent biting and probing protection of stored LLIRNs was preserved for 83 weeks with the 5,930 mg/m(2) DEET

  1. Incremental impact upon malaria transmission of supplementing pyrethroid-impregnated long-lasting insecticidal nets with indoor residual spraying using pyrethroids or the organophosphate, pirimiphos methyl.

    PubMed

    Hamainza, Busiku; Sikaala, Chadwick H; Moonga, Hawela B; Chanda, Javan; Chinula, Dingani; Mwenda, Mulenga; Kamuliwo, Mulakwa; Bennett, Adam; Seyoum, Aklilu; Killeen, Gerry F

    2016-02-18

    Long-lasting, insecticidal nets (LLINs) and indoor residual spraying (IRS) are the most widely accepted and applied malaria vector control methods. However, evidence that incremental impact is achieved when they are combined remains limited and inconsistent. Fourteen population clusters of approximately 1000 residents each in Zambia's Luangwa and Nyimba districts, which had high pre-existing usage rates (81.7 %) of pyrethroid-impregnated LLINs were quasi-randomly assigned to receive IRS with either of two pyrethroids, namely deltamethrin [Wetable granules (WG)] and lambdacyhalothrin [capsule suspension (CS)], with an emulsifiable concentrate (EC) or CS formulation of the organophosphate pirimiphos methyl (PM), or with no supplementary vector control measure. Diagnostic positivity of patients tested for malaria by community health workers in these clusters was surveyed longitudinally over pre- and post-treatment periods spanning 29 months, over which the treatments were allocated and re-allocated in advance of three sequential rainy seasons. Supplementation of LLINs with PM CS offered the greatest initial level of protection against malaria in the first 3 months of application (incremental protective efficacy (IPE) [95 % confidence interval (CI)] = 0.63 [CI 0.57, 0.69], P < 0.001), followed by lambdacyhalothrin (IPE [95 % CI] = 0.31 [0.10, 0.47], P = 0.006) and PM EC (IPE, 0.23 [CI 0.15, 0.31], P < 0.001) and then by deltamethrin (IPE [95 % CI] = 0.19 [-0.01, 0.35], P = 0.064). Neither pyrethroid formulation provided protection beyond 3 months after spraying, but the protection provided by both PM formulations persisted undiminished for longer periods: 6 months for CS and 12 months for EC. The CS formulation of PM provided greater protection than the combined pyrethroid IRS formulations throughout its effective life IPE [95 % CI] = 0.79 [0.75, 0.83] over 6 months. The EC formulation of PM provided incremental protection for the first 3 months (IPE [95 % CI] = 0

  2. Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial.

    PubMed

    Schöffski, Patrick; Wozniak, Agnieszka; Escudier, Bernard; Rutkowski, Piotr; Anthoney, Alan; Bauer, Sebastian; Sufliarsky, Jozef; van Herpen, Carla; Lindner, Lars H; Grünwald, Viktor; Zakotnik, Branko; Lerut, Evelyne; Debiec-Rychter, Maria; Marréaud, Sandrine; Lia, Michela; Raveloarivahy, Tiana; Collette, Sandra; Albiges, Laurence

    2017-12-01

    tolerated in advanced, metastatic PRCC1, achieving objective responses and long-lasting disease control in patients with MET mutations or amplification. Sporadic, durable responses are also seen in MET- and MET? cases, suggesting the presence of other alterations of MET or alternative pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Plastics Technology.

    ERIC Educational Resources Information Center

    Barker, Tommy G.

    This curriculum guide is designed to assist junior high schools industrial arts teachers in planning new courses and revising existing courses in plastics technology. Addressed in the individual units of the guide are the following topics: introduction to production technology; history and development of plastics; safety; youth leadership,…

  4. Measures of Malaria Burden after Long-Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study

    PubMed Central

    Katureebe, Agaba; Zinszer, Kate; Arinaitwe, Emmanuel; Charland, Katia; Kigozi, Ruth; Kilama, Maxwell; Nankabirwa, Joaniter; Yeka, Adoke; Mawejje, Henry; Mpimbaza, Arthur; Donnelly, Martin J.; Rosenthal, Philip J.; Lindsay, Steve W.; Staedke, Sarah G.; Smith, David L.; Kamya, Moses R.; Dorsey, Grant

    2016-01-01

    Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites. Methods and Findings Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera). Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera. High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107). The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN. In Walukuba, over the 28-mo post-intervention period

  5. Dynamic DNA methylation regulates neuronal intrinsic membrane excitability

    PubMed Central

    Meadows, Jarrod P.; Guzman-Karlsson, Mikael C.; Phillips, Scott; Brown, Jordan A.; Strange, Sarah K.; Sweatt, J. David; Hablitz, John J.

    2017-01-01

    Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory-related plasticity also includes alterations in intrinsic membrane excitability mediated by changes in the abundance or activity of ion channels in the plasma membrane, which sets the threshold for action potential generation. We found that prolonged inhibition of DNA methyltransferase (DNMT) activity increased intrinsic membrane excitability of cultured cortical pyramidal neurons. Knockdown of the cytosine demethylase TET1 or inhibition of RNA polymerase blocked the increased membrane excitability caused by DNMT inhibition, suggesting that this effect was mediated by subsequent cytosine demethylation and de novo transcription. Prolonged DNMT inhibition blunted the medium component of the after-hyperpolarization potential, an effect that would increase neuronal excitability, and was associated with reduced expression of the genes encoding small-conductance Ca2+-activated K+ (SK) channels. Furthermore, the specific SK channel blocker apamin increased neuronal excitability but was ineffective after DNMT inhibition. Our results suggested that DNMT inhibition enables transcriptional changes that culminate in decreased expression of SK channel–encoding genes and decreased activity of SK channels, thus providing a mechanism for the regulation of neuronal intrinsic membrane excitability by dynamic DNA cytosine methylation. This study has implications for human neurological and psychiatric diseases associated with dysregulated intrinsic excitability. PMID:27555660

  6. Early life nutrition and neural plasticity.

    PubMed

    Georgieff, Michael K; Brunette, Katya E; Tran, Phu V

    2015-05-01

    The human brain undergoes a remarkable transformation during fetal life and the first postnatal years from a relatively undifferentiated but pluripotent organ to a highly specified and organized one. The outcome of this developmental maturation is highly dependent on a sequence of environmental exposures that can have either positive or negative influences on the ultimate plasticity of the adult brain. Many environmental exposures are beyond the control of the individual, but nutrition is not. An ever-increasing amount of research demonstrates not only that nutrition shapes the brain and affects its function during development but also that several nutrients early in life have profound and long-lasting effects on the brain. Nutrients have been shown to alter opening and closing of critical and sensitive periods of particular brain regions. This paper discusses the roles that various nutrients play in shaping the developing brain, concentrating specifically on recently explicated biological mechanisms by which particularly salient nutrients influence childhood and adult neural plasticity.

  7. Studies of Neuronal Gene Regulation Controlling the Molecular Mechanisms Underlying Neural Plasticity.

    PubMed

    Fukuchi, Mamoru

    2017-01-01

    The regulation of the development and function of the nervous system is not preprogramed but responds to environmental stimuli to change neural development and function flexibly. This neural plasticity is a characteristic property of the nervous system. For example, strong synaptic activation evoked by environmental stimuli leads to changes in synaptic functions (known as synaptic plasticity). Long-lasting synaptic plasticity is one of the molecular mechanisms underlying long-term learning and memory. Since discovering the role of the transcription factor cAMP-response element-binding protein in learning and memory, it has been widely accepted that gene regulation in neurons contributes to long-lasting changes in neural functions. However, it remains unclear how synaptic activation is converted into gene regulation that results in long-lasting neural functions like long-term memory. We continue to address this question. This review introduces our recent findings on the gene regulation of brain-derived neurotrophic factor and discusses how regulation of the gene participates in long-lasting changes in neural functions.

  8. Predicting Intrinsic Motivation

    ERIC Educational Resources Information Center

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the…

  9. Plastic welder

    NASA Technical Reports Server (NTRS)

    Buckley, J. D.; Fox, R. L.; Swain, R. J.

    1980-01-01

    Low-cost, self-contained, portable welder joins plastic parts by induction heating. Welder is useable in any atmosphere or in vacuum and with most types of thermoplastic; plastic components can be joined in situ. Device is applicable to aerospace industry and in automobile, furniture, and construction industries. Power requirements are easily met by battery or solar energy. In welder, toroidal inductor transfers magnetic flux through thermoplastic to screen. Heated screen causes plastic surface on either side to melt and flow into it to form joint.

  10. The effect of massage therapy and/or exercise therapy on subacute or long-lasting neck pain--the Stockholm neck trial (STONE): study protocol for a randomized controlled trial.

    PubMed

    Skillgate, Eva; Bill, Anne-Sylvie; Côté, Pierre; Viklund, Peter; Peterson, Anna; Holm, Lena W

    2015-09-16

    Neck pain is a major health problem in populations worldwide and an economic burden in modern societies due to its high prevalence and costs in terms of health care expenditures and lost productivity. Massage and exercise therapy are widely used management options for neck pain. However, there is a lack of scientific evidence regarding their effectiveness for subacute and long-lasting neck pain. This study protocol describes a randomized controlled trial aiming to determine the effect of massage and/or exercise therapy on subacute and long-lasting neck pain over the course of 1 year. A randomized controlled trial in which at least 600 study participants with subacute or long-lasting nonspecific neck pain will be recruited and randomly allocated to one of four treatment arms: massage therapy (A), exercise therapy (B), exercise therapy plus massage therapy (C) and advice to stay active (D). The study has an E-health approach, and study participants are being recruited through advertising with a mix of traditional and online marketing channels. Web-based self-report questionnaires measure the main outcomes at 7, 12, 26 and 52 weeks after inclusion. The primary outcomes are a clinically important improvement in pain intensity and pain-related disability at follow-up, measured with a modified version of the Chronic Pain Questionnaire (CPQ). The secondary outcomes are global improvement, health-related quality of life (EQ-5D), sick leave, drug consumption and healthcare utilization. Adverse events are measured by questionnaires at return visits to the clinic, and automated text messages (SMSes) survey neck pain intensity and pain-related disability every week over one year. The results of this study will provide clinicians and stakeholders much needed knowledge to plan medical care for subacute and long-lasting neck pain disorders. Current Controlled Trials ISRCTN01453590. Date of registration: 3 July 2014.

  11. Epigenetic Basis of Neuronal and Synaptic Plasticity.

    PubMed

    Karpova, Nina N; Sales, Amanda J; Joca, Samia R

    2017-01-01

    Neuronal network and plasticity change as a function of experience. Altered neural connectivity leads to distinct transcriptional programs of neuronal plasticity-related genes. The environmental challenges throughout life may promote long-lasting reprogramming of gene expression and the development of brain disorders. The modifications in neuronal epigenome mediate gene-environmental interactions and are required for activity-dependent regulation of neuronal differentiation, maturation and plasticity. Here, we highlight the latest advances in understanding the role of the main players of epigenetic machinery (DNA methylation and demethylation, histone modifications, chromatin-remodeling enzymes, transposons, and non-coding RNAs) in activity-dependent and long- term neural and synaptic plasticity. The review focuses on both the transcriptional and post-transcriptional regulation of gene expression levels, including the processes of promoter activation, alternative splicing, regulation of stability of gene transcripts by natural antisense RNAs, and alternative polyadenylation. Further, we discuss the epigenetic aspects of impaired neuronal plasticity and the pathogenesis of neurodevelopmental (Rett syndrome, Fragile X Syndrome, genomic imprinting disorders, schizophrenia, and others), stressrelated (mood disorders) and neurodegenerative Alzheimer's, Parkinson's and Huntington's disorders. The review also highlights the pharmacological compounds that modulate epigenetic programming of gene expression, the potential treatment strategies of discussed brain disorders, and the questions that should be addressed during the development of effective and safe approaches for the treatment of brain disorders.

  12. Developmental plasticity

    PubMed Central

    Lea, Amanda J; Tung, Jenny; Archie, Elizabeth A

    2017-01-01

    Abstract Early life experiences can have profound and persistent effects on traits expressed throughout the life course, with consequences for later life behavior, disease risk, and mortality rates. The shaping of later life traits by early life environments, known as ‘developmental plasticity’, has been well-documented in humans and non-human animals, and has consequently captured the attention of both evolutionary biologists and researchers studying human health. Importantly, the parallel significance of developmental plasticity across multiple fields presents a timely opportunity to build a comprehensive understanding of this phenomenon. We aim to facilitate this goal by highlighting key outstanding questions shared by both evolutionary and health researchers, and by identifying theory and empirical work from both research traditions that is designed to address these questions. Specifically, we focus on: (i) evolutionary explanations for developmental plasticity, (ii) the genetics of developmental plasticity and (iii) the molecular mechanisms that mediate developmental plasticity. In each section, we emphasize the conceptual gains in human health and evolutionary biology that would follow from filling current knowledge gaps using interdisciplinary approaches. We encourage researchers interested in developmental plasticity to evaluate their own work in light of research from diverse fields, with the ultimate goal of establishing a cross-disciplinary understanding of developmental plasticity. PMID:29424834

  13. Accumulation and fragmentation of plastic debris in global environments.

    PubMed

    Barnes, David K A; Galgani, Francois; Thompson, Richard C; Barlaz, Morton

    2009-07-27

    One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences (fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly

  14. Accumulation and fragmentation of plastic debris in global environments

    PubMed Central

    Barnes, David K. A.; Galgani, Francois; Thompson, Richard C.; Barlaz, Morton

    2009-01-01

    One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences (fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly

  15. Spike-timing dependent plasticity in inhibitory circuits.

    PubMed

    Lamsa, Karri P; Kullmann, Dimitri M; Woodin, Melanie A

    2010-01-01

    Inhibitory circuits in the brain rely on GABA-releasing interneurons. For long, inhibitory circuits were considered weakly plastic in the face of patterns of neuronal activity that trigger long-term changes in the synapses between excitatory principal cells. Recent studies however have shown that GABAergic circuits undergo various forms of long-term plasticity. For the purpose of this review, we identify three major long-term plasticity expression sites. The first locus is the glutamatergic synapses that excite GABAergic inhibitory cells and drive their activity. Such synapses, on many but not all inhibitory interneurons, exhibit long-term potentiation (LTP) and depression (LTD). Second, GABAergic synapses themselves can undergo changes in GABA release probability or postsynaptic GABA receptors. The third site of plasticity is in the postsynaptic anion gradient of GABAergic synapses; coincident firing of GABAergic axons and postsynaptic neurons can cause a long-lasting change in the reversal potential of GABA(A) receptors mediating fast inhibitory postsynaptic potentials. We review the recent literature on these forms of plasticity by asking how they may be triggered by specific patterns of pre- and postsynaptic action potentials, although very few studies have directly examined spike-timing dependent plasticity (STDP) protocols in inhibitory circuits. Plasticity of interneuron recruitment and of GABAergic signaling provides for a rich flexibility in inhibition that may be central to many aspects of brain function. We do not consider plasticity at glutamatergic synapses on Purkinje cells and other GABAergic principal cells.

  16. Evaluation of a DNA vaccine candidate co-expressing GP3 and GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) with interferon α/γ in immediate and long-lasting protection against HP-PRRSV challenge.

    PubMed

    Du, Yijun; Qi, Jing; Lu, Yu; Wu, Jiaqiang; Yoo, Dongwan; Liu, Xing; Zhang, Xiumei; Li, Jun; Sun, Wenbo; Cong, Xiaoyan; Shi, Jianli; Wang, Jinbao

    2012-12-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) has become one of the most economically important diseases to the global pork industry. Current vaccination strategies only provide a limited protective efficacy. In this study, a DNA vaccine, pVAX1(©)-α-γ-GP35, co-expressing GP3 and GP5 of PRRSV with interferon α/γ was constructed, and its immediate and long-lasting protection against highly pathogenic PRRSV (HP-PRRSV) challenge were examined in pigs. For immediate protection, the results showed that pVAX1(©)-α-γ-GP35 could provide partially protective efficacy, which was similar to the pVAX1(©)-α-γ (expressing interferon α/γ). For long-lasting protection, pigs inoculated with pVAX1(©)-α-γ-GP35 developed significantly higher PRRSV-specific antibody response, T cell proliferation, IFN-γ, and IL-4, than those vaccinated with pVAX1(©)-GP35 (expressing GP3 and GP5 of PRRSV). Following homologous challenge with HP-PRRSV strain SD-JN, pigs inoculated with pVAX1(©)-α-γ-GP35 showed almost no clinical signs, no lung lesions, and significantly lower viremia, as compared to those in pVAX1(©)-GP35 group. It indicated that pVAX1(©)-α-γ-GP35 could induce enhanced immune responses and provide both immediate and long-lasting protection against HP-PRRSV challenge in pigs. The DNA vaccine pVAX1(©)-α-γ-GP35 might be an attractive candidate vaccine for the prevention and control of HP-PRRSV infections.

  17. Report on the first WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Hong Kong SAR, China, 24-26 January 2013.

    PubMed

    Girard, Marc P; Tam, John S; Pervikov, Yuri; Katz, Jacqueline M

    2013-08-20

    On January 24-26, 2013, the World Health Organization convened the first integrated meeting on "The development and clinical trials of vaccines that induce broadly protective and long-lasting immune responses" to review the current status of development and clinical evaluation of novel influenza vaccines as well as strategies to produce and deliver vaccines in novel ways. Special attention was given to the development of possible universal influenza vaccines. Other topics that were addressed included an update on clinical trials of pandemic and seasonal influenza vaccines in high-risk groups and vaccine safety, as well as regulatory issues. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  18. Neuronal plasticity and thalamocortical sleep and waking oscillations

    PubMed Central

    Timofeev, Igor

    2011-01-01

    Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma. PMID:21854960

  19. Plastics Technician.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document contains 16 units to consider for use in a tech prep competency profile for the occupation of plastics technician. All the units listed will not necessarily apply to every situation or tech prep consortium, nor will all the competencies within each unit be appropriate. Several units appear within each specific occupation and would…

  20. Intrinsically Disordered Energy Landscapes

    PubMed Central

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-01-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium. PMID:25999294

  1. GLASS FIBER REINFORCED PLASTICS,

    DTIC Science & Technology

    Contents: Fibrous glass fillers Binders used in the glass plastic industry Method of manufacturing glass plastics and glass plastic articles Properties of fiberglass Primary areas for use of glass fibre reinforced plastics

  2. Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning

    PubMed Central

    Mills, Fergil; Globa, Andrea K.; Liu, Shuai; Cowan, Catherine M.; Mobasser, Mahsan; Phillips, Anthony G.; Borgland, Stephanie L.; Bamji, Shernaz X.

    2017-01-01

    Drugs of abuse alter synaptic connections in the ‘reward circuit’ of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation (LTP) in the ventral tegmental area (VTA), and is recruited to the synaptic membrane of excitatory inputs onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a significant reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction. PMID:28192395

  3. Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning.

    PubMed

    Mills, Fergil; Globa, Andrea K; Liu, Shuai; Cowan, Catherine M; Mobasser, Mahsan; Phillips, Anthony G; Borgland, Stephanie L; Bamji, Shernaz X

    2017-04-01

    Drugs of abuse alter synaptic connections in the reward circuitry of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation in the ventral tegmental area and is recruited to the synaptic membranes of excitatory synapses onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction.

  4. Intrinsically variable stars

    NASA Technical Reports Server (NTRS)

    Bohm-Vitense, Erika; Querci, Monique

    1987-01-01

    The characteristics of intrinsically variable stars are examined, reviewing the results of observations obtained with the IUE satellite since its launch in 1978. Selected data on both medium-spectral-class pulsating stars (Delta Cep stars, W Vir stars, and related groups) and late-type variables (M, S, and C giants and supergiants) are presented in spectra, graphs, and tables and described in detail. Topics addressed include the calibration of the the period-luminosity relation, Cepheid distance determination, checking stellar evolution theory by the giant companions of Cepheids, Cepheid masses, the importance of the hydrogen convection zone in Cepheids, temperature and abundance estimates for Population II pulsating stars, mass loss in Population II Cepheids, SWP and LWP images of cold giants and supergiants, temporal variations in the UV lines of cold stars, C-rich cold stars, and cold stars with highly ionized emission lines.

  5. Gaussian Intrinsic Entanglement

    NASA Astrophysics Data System (ADS)

    Mišta, Ladislav; Tatham, Richard

    2016-12-01

    We introduce a cryptographically motivated quantifier of entanglement in bipartite Gaussian systems called Gaussian intrinsic entanglement (GIE). The GIE is defined as the optimized mutual information of a Gaussian distribution of outcomes of measurements on parts of a system, conditioned on the outcomes of a measurement on a purifying subsystem. We show that GIE vanishes only on separable states and exhibits monotonicity under Gaussian local trace-preserving operations and classical communication. In the two-mode case, we compute GIE for all pure states as well as for several important classes of symmetric and asymmetric mixed states. Surprisingly, in all of these cases, GIE is equal to Gaussian Rényi-2 entanglement. As GIE is operationally associated with the secret-key agreement protocol and can be computed for several important classes of states, it offers a compromise between computable and physically meaningful entanglement quantifiers.

  6. Intrinsic Feature Motion Tracking

    SciTech Connect

    Goddard, Jr., James S.

    2013-03-19

    Subject motion during 3D medical scanning can cause blurring and artifacts in the 3D images resulting in either rescans or poor diagnosis. Anesthesia or physical restraints may be used to eliminate motion but are undesirable and can affect results. This software measures the six degree of freedom 3D motion of the subject during the scan under a rigidity assumption using only the intrinsic features present on the subject area being monitored. This movement over time can then be used to correct the scan data removing the blur and artifacts. The software acquires images from external cameras or images stored onmore » disk for processing. The images are from two or three calibrated cameras in a stereo arrangement. Algorithms extract and track the features over time and calculate position and orientation changes relative to an initial position. Output is the 3D position and orientation change measured at each image.« less

  7. Plasticity of Sensorimotor Networks: Multiple Overlapping Mechanisms

    PubMed Central

    Buch, Ethan R.; Liew, Sook-Lei; Cohen, Leonardo G.

    2016-01-01

    Redundancy is an important feature of the motor system, as abundant degrees of freedom are prominent at every level of organization across the central and peripheral nervous systems, and musculoskeletal system. This basic feature results in a system that is both flexible and robust, and which can be sustainably adapted through plasticity mechanisms in response to intrinsic organismal changes and dynamic environments. While much early work of motor system organization has focused on synaptic-based plasticity processes that are driven via experience, recent investigations of neuron–glia interactions, epigenetic mechanisms and large-scale network dynamics have revealed a plethora of plasticity mechanisms that support motor system organization across multiple, overlapping spatial and temporal scales. Furthermore, an important role of these mechanisms is the regulation of intrinsic variability. Here, we review several of these mechanisms and discuss their potential role in neurorehabilitation. PMID:26985069

  8. Induction and expression rules of synaptic plasticity in hippocampal interneurons

    PubMed Central

    Laezza, Fernanda; Dingledine, Raymond

    2014-01-01

    The knowledge that excitatory synapses on aspiny hippocampal interneurons can develop genuine forms of activity-dependent remodeling, independently from the surrounding network of principal cells, is a relatively new concept. Cumulative evidence has now unequivocally demonstrated that, despite the absence of specialized postsynaptic spines that serve as compartmentalized structure for intracellular signaling in principal cell plasticity, excitatory inputs onto interneurons can undergo forms of synaptic plasticity that are induced and expressed autonomously from principal cells. Yet, the rules for induction and expression of interneuron plasticity are much more heterogeneous than in principal neurons. Long-term plasticity in interneurons is not necessarily dependent upon postsynaptic activation of NMDA receptors nor relies on the same postsynaptic membrane potential requirements as principal cells. Plasticity in interneurons rather requires activation of Ca2+-permeable AMPA receptors and/or metabotropic glutamate receptors and is triggered by postsynaptic hyperpolarization. In this review we will outline these distinct features of interneuron plasticity and identify potential critical candidate molecules that might be important for sustaining long-lasting changes in synaptic strength at excitatory inputs onto interneurons. This article is part of a Special Issue entitled ‘Synaptic Plasticity & Interneurons’. PMID:21195098

  9. Long lasting dynamic disequilibrium in river basins

    NASA Astrophysics Data System (ADS)

    Goren, Liran; Willett, Sean D.; McCoy, Scott W.; Perron, J. Taylor; Chen, Chia-Yu

    2014-05-01

    The river basins of ancient landscapes such as the southeastern United States exhibit disequilibrium in the form of migrating divides and stream capture. This observation is surprising in light of the relatively short theoretical fluvial response time, which is controlled by the celerity of the erosional wave that propagates upstream the fluvial channels. The response time is believed to determine the time required for fluvial landscapes to adjust to tectonic, climatic, and base-level perturbations, and its global estimations range between 0.1 Myr and 10s Myr. To address this discrepancy, we develop a framework for mapping continuous dynamic reorganization of natural river basins, and demonstrate the longevity of disequilibrium along the river basins in the southeastern United States that are reorganizing in response to escarpment retreat and coastal advance. The mapping of disequilibrium is based on a proxy for steady-state elevation, Ξ, that can be easily calculated from digital elevation models. Disequilibrium is inferred from differences in the value of Ξ across water divides. These differences indicate that with the present day drainage area distribution and river topology the steady-state channels elevation across the divides differs, and therefore divides are expected to migrate in the direction of the higher Ξ value. We further use the landscape evolution model DAC to explore the source of the longevity of disequilibrium in fluvial landscapes. DAC solves accurately for the location of water divides, using a combination of an analytical solution for hillslopes and low-order channels together with a numerical solution for higher order channels. DAC simulations demonstrate topological, geometrical, and topographical adjustments that persist much longer than the theoretical response time, and consequently, extend the time needed to diminish disequilibrium in the landscape and to reach topological and topographical steady-state. This behavior is interpreted as resulting from a positive feedback between divide migration, which causes topological modifications and area change, on the one hand, and channel slope adjustments, which change the erosion rates on opposing sides of water divides and promote their migration, on the other hand. Furthermore, the constantly shifting drainage area and the changing topology of the drainage network are shown to be a possible source for autogenic sediment flux variations.

  10. Cell-specific synaptic plasticity induced by network oscillations.

    PubMed

    Zarnadze, Shota; Bäuerle, Peter; Santos-Torres, Julio; Böhm, Claudia; Schmitz, Dietmar; Geiger, Jörg Rp; Dugladze, Tamar; Gloveli, Tengis

    2016-05-24

    Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner.

  11. Intrinsically Disordered Side of the Zika Virus Proteome

    PubMed Central

    Giri, Rajanish; Kumar, Deepak; Sharma, Nitin; Uversky, Vladimir N.

    2016-01-01

    Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of disorder-based drugs. PMID:27867910

  12. Sol–gel synthesis of long-lasting phosphors CdSiO{sub 3}: Mn{sup 2+}, RE{sup 3+} (RE = Tb, Eu, Nd) and luminescence mechanism research

    SciTech Connect

    Qu, Xiaofei; Cao, Lixin; Liu, Wei; Su, Ge; Wang, Pingping; Schultz, Isabel

    2012-06-15

    Highlights: ► New long-lasting CdSiO{sub 3}: Mn{sup 2+}, RE{sup 3+} (RE = Tb, Eu, Nd) phosphors were synthesized by a sol–gel method. ► The afterglow performance of the CdSiO{sub 3}: Mn{sup 2+}, Eu{sup 3+} phosphor was the best. ► The role of RE{sup 3+} co-doped into the CdSiO{sub 3}: Mn{sup 2+} matrix was discussed in this paper. -- Abstract: Mn{sup 2+} and RE{sup 3+} (RE = Tb, Eu, Nd) co-doped CdSiO{sub 3} orange phosphors were prepared at 1050 °C by a sol–gel method. The phase and crystallinity of the synthesized materials were investigated by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The luminescence characteristics were analyzed using photoluminescence (PL) spectra, afterglow decay curves, long-lasting phosphorescence spectra, and thermoluminescence (TL) spectra. Due to the difference in co-doped rare earth ionic radii, it varied greatly in trap density and trap depth caused by the different defects deriving from RE{sup 3+} ions co-doping into the CdSiO{sub 3}: Mn{sup 2+} host. The afterglow intensity and time for these samples increased as follows: CdSiO{sub 3}: Mn{sup 2+}0.2%, Nd{sup 3+}0.8% < CdSiO{sub 3}: Mn{sup 2+}0.4%, Tb{sup 3+}0.8% < CdSiO{sub 3}: Mn{sup 2+}0.4%, Eu{sup 3+}0.3%. CdSiO{sub 3}: Mn{sup 2+}0.4%, Eu{sup 3+}0.3% had the best afterglow properties, which could be due to the proper traps formed by Eu{sup 3+} ions co-doping into the host. The role of RE{sup 3+} co-doped into the CdSiO{sub 3}: Mn{sup 2+} matrix and the possible long-lasting phosphorescence process was also discussed in this paper.

  13. beta-Arrestin 1 is required for PAC1 receptor-mediated potentiation of long-lasting ERK1/2 activation by glucose in pancreatic beta-cells.

    PubMed

    Broca, Christophe; Quoyer, Julie; Costes, Safia; Linck, Nathalie; Varrault, Annie; Deffayet, Pierre-Marie; Bockaert, Joël; Dalle, Stéphane; Bertrand, Gyslaine

    2009-02-13

    In pancreatic beta-cells, the pituitary adenylate cyclase-activating polypeptide (PACAP) exerts a potent insulin secretory effect via PAC(1) and VPAC receptors (Rs) through the Galpha(s)/cAMP/protein kinase A pathway. Here, we investigated the mechanisms linking PAC(1)R to ERK1/2 activation in INS-1E beta-cells and pancreatic islets. PACAP caused a transient (5 min) increase in ERK1/2 phosphorylation via PAC(1)Rs and promoted nuclear translocation of a fraction of cytosolic p-ERK1/2. Both protein kinase A- and Src-dependent pathways mediated this transient ERK1/2 activation. Moreover, PACAP potentiated glucose-induced long-lasting ERK1/2 activation. Blocking Ca(2+) influx abolished glucose-induced ERK1/2 activation and PACAP potentiating effect. Glucose stimulation during KCl depolarization showed that, in addition to the triggering signal (rise in cytosolic [Ca(2+)]), the amplifying pathway was also involved in glucose-induced sustained ERK1/2 activation and was required for PACAP potentiation. The finding that at 30 min glucose-induced p-ERK1/2 was detected in both cytosol and nucleus while the potentiating effect of PACAP was only observed in the cytosol, suggested the involvement of the scaffold protein beta-arrestin. Indeed, beta-arrestin 1 (beta-arr1) depletion (in beta-arr1 knockout mouse islets or in INS-1E cells by siRNA) completely abolished PACAP potentiation of long-lasting ERK1/2 activation by glucose. Finally, PACAP potentiated glucose-induced CREB transcriptional activity and IRS-2 mRNA expression mainly via the ERK1/2 signaling pathway, and likewise, beta-arr1 depletion reduced the PACAP potentiating effect on IRS-2 expression. These results establish for the first time that PACAP potentiates glucose-induced long-lasting ERK1/2 activation via a beta-arr1-dependent pathway and thus provide new insights concerning the mechanisms of PACAP and glucose actions in pancreatic beta-cells.

  14. Intrinsic-surface-tag image authentication

    SciTech Connect

    Palm, R.G.; DeVolpi, A.

    1991-12-01

    The objective of this work is to further the development of a unique treaty limited item (TLI) intrinsic surface tag for arms control applications. This tag's unique feature is the ability to capture the sub-micron scale topography of the TLI surface. The surface topography is captured by plastic castings of the surface as digitally imaged by an electron microscope. Tag authentication is accomplished by comparing digital castings images obtained in two different inspections. Surface replication experiments are described, as these experiments from the basis for the authentication algorithm. Both the experiments and the authentication algorithm are analyzed using the modulation transfer function. Recommendations for future improvements in tag authentication are also suggested by the modulation transfer function analysis. 4 refs.

  15. Intrinsic-surface-tag image authentication

    SciTech Connect

    Palm, R.G.; DeVolpi, A.

    1991-12-01

    The objective of this work is to further the development of a unique treaty limited item (TLI) intrinsic surface tag for arms control applications. This tag`s unique feature is the ability to capture the sub-micron scale topography of the TLI surface. The surface topography is captured by plastic castings of the surface as digitally imaged by an electron microscope. Tag authentication is accomplished by comparing digital castings images obtained in two different inspections. Surface replication experiments are described, as these experiments from the basis for the authentication algorithm. Both the experiments and the authentication algorithm are analyzed using the modulation transfer function. Recommendations for future improvements in tag authentication are also suggested by the modulation transfer function analysis. 4 refs.

  16. Decoding the epigenetic language of neuronal plasticity.

    PubMed

    Borrelli, Emiliana; Nestler, Eric J; Allis, C David; Sassone-Corsi, Paolo

    2008-12-26

    Neurons are submitted to an exceptional variety of stimuli and are able to convert these into high-order functions, such as storing memories, controlling behavior, and governing consciousness. These unique properties are based on the highly flexible nature of neurons, a characteristic that can be regulated by the complex molecular machinery that controls gene expression. Epigenetic control, which largely involves events of chromatin remodeling, appears to be one way in which transcriptional regulation of gene expression can be modified in neurons. This review will focus on how epigenetic control in the mature nervous system may guide dynamic plasticity processes and long-lasting cellular neuronal responses. We outline the molecular pathways underlying chromatin transitions, propose the presence of an "epigenetic indexing code," and discuss how central findings accumulating at an exponential pace in the field of epigenetics are conceptually changing our perspective of adult brain function.

  17. Removal of S6K1 and S6K2 Leads to Divergent Alterations in Learning, Memory, and Synaptic Plasticity

    ERIC Educational Resources Information Center

    Antion, Marcia D.; Merhav, Maayan; Hoeffer, Charles A.; Reis, Gerald; Kozma, Sara C.; Thomas, George; Schuman Erin M.; Rosenblum, Kobi; Klann, Eric

    2008-01-01

    Protein synthesis is required for the expression of enduring memories and long-lasting synaptic plasticity. During cellular proliferation and growth, S6 kinases (S6Ks) are activated and coordinate the synthesis of de novo proteins. We hypothesized that protein synthesis mediated by S6Ks is critical for the manifestation of learning, memory, and…

  18. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  19. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. the second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  20. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-12-25

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat. 11 figs.

  1. Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells

    NASA Astrophysics Data System (ADS)

    He, Qionger; Duguid, Ian; Clark, Beverley; Panzanelli, Patrizia; Patel, Bijal; Thomas, Philip; Fritschy, Jean-Marc; Smart, Trevor G.

    2015-07-01

    Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABAA receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABAA receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABAA receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABAA receptors and is abolished by preventing CaMKII phosphorylation of GABAA receptors. Our results reveal a novel GABAA receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum.

  2. Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells

    PubMed Central

    He, Qionger; Duguid, Ian; Clark, Beverley; Panzanelli, Patrizia; Patel, Bijal; Thomas, Philip; Fritschy, Jean-Marc; Smart, Trevor G.

    2015-01-01

    Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABAA receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron–Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABAA receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABAA receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABAA receptors and is abolished by preventing CaMKII phosphorylation of GABAA receptors. Our results reveal a novel GABAA receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum. PMID:26179122

  3. Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

    NASA Astrophysics Data System (ADS)

    Toto, Angelo; Camilloni, Carlo; Giri, Rajanish; Brunori, Maurizio; Vendruscolo, Michele; Gianni, Stefano

    2016-02-01

    Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions.

  4. [Medical visits before return to work, after a long lasting absence, above 60 days, for injuries or common diseases in a public transport company. Analysis and discussions of utility and consequences in term of evaluation of fitness to specific job].

    PubMed

    Verga, A; Bordini, L; Ricci, M G; Di Lucca, P; Todaro, A

    2012-01-01

    The aim of this study is to evaluate the opportunity to do medical visits before return to work, after a long continuous absence, above 60 days, for injuries (occupational and non-occupational) or common diseases. We have examined medical records of 403 workers, in 2010 and 2011, occupied in a public transport company, in order to control the following variables: job, age, clinical conditions related to the absences, classification of the absence as injuries or common disease and conclusions about medical fitness to specific job. Our findings have shown an equal percentage of causes of absences in term of injuries or common diseases. The main cause of absence and of non fit to specific job, after medical evaluation, is depending on orthopaedic post-traumatic diseases. This evidence support the importance to do medical visits after long-lasting absence from work, particularly in case of jobs (bus, tram, subway drivers) at risk for other people.

  5. In vivo evidence for serotonin 5-HT2C receptor-mediated long-lasting excitability of lumbar spinal reflex and its functional interaction with 5-HT1A receptor in the mammalian spinal cord.

    PubMed

    Gajendiran, Mahadevan

    2008-03-28

    The purpose of the present study was to investigate the 5-HT(2C) receptor-mediated effects on the spinal monosynaptic mass reflex activities and also its functional interactions with 5-HT(1A) receptors in anesthetized, acutely spinalized mammalian adult spinal cord in vivo. Intravenous administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (0.1 mg/kg), an agonist of 5-HT(2A/2C) receptors, significantly increased the excitability of spinal motoneurons as reflected by an increase in the spinal monosynaptic mass reflex amplitude to 150-200% of the control. 5-HT(2A/2C) receptor-induced motoneuron excitability was slow, persistent and long-lasting for more than 2h that was significantly inhibited by 5-HT(2C) receptor specific antagonist SB 242084 administered 10 min prior to DOI. Simultaneous administration of DOI (0.1 mg/kg, i.v.) along with (+/-)-8-hydroxy dipropylaminotetraline hydrobromide (8-OH-DPAT) (0.1 mg/kg, i.v.) completely inhibited DOI-induced spinal monosynaptic mass reflex facilitation. In another separate study, administration of 8-OH-DPAT (0.1 mg/kg, i.v.) at the maximum response of DOI also inhibited the motoneuron's excitability; however, the inhibition lasted only for a period of 40-60 min after administration of 8-OH-DPAT, after which the spinal monosynaptic mass reflex amplitude reached its maximum level. These findings suggest that the 5-HT(2C) receptor is primarily involved in the mediation of the long-lasting excitability of spinal motoneurons and possibly interacts with its functional counterpart, 5-HT(1A) receptors in the mammalian adult spinal cord.

  6. High non-protective, long-lasting antibody levels in malaria are associated with haplotype shifting in MHC-peptide-TCR complex formation: a new mechanism for immune evasion.

    PubMed

    Patarroyo, Manuel E; Bermúdez, Adriana; Salazar, Luz Mary; Espejo, Fabiola

    2006-07-01

    An effective malarial vaccine must contain multiple immunogenic, protection-inducing epitopes able to block and destroy the P. falciparum malaria parasite, the most lethal form of this disease in the world. Our strategy has consisted in using conserved peptides blocking parasite binding to red blood cells; however, these peptides are non-immunogenic and non-protection-inducing. Modifying their critical residues can make them immunogenic. Such peptides induced antibody titers (determined by immunofluorescence antibody test, IFA) and made the latter reactive (determined by Western blot) and protection inducing against experimental challenge with a highly infective Aotus monkey adapted P. falciparum strain. Modified peptides also induce highly non-protective long-lasting antibody levels. Modifications performed might allow them to bind specifically to different HLA-DRbeta purified molecules. These immunological and biological activities are associated with modifications in their three-dimensional structure as determined by (1)H-NMR. It was found that modified, high non-protective long-lasting antibody level peptides bound to HLA-DR molecules from a different haplotype (to which immunogenic, protection-inducers bind) and had 4.6 +/- 1.4 A shorter distances between residues fitting into these molecules' Pocket 1 to Pocket 9, suggesting fitting into an inappropriate HLA-DR molecule. A multi-component, subunit-based, malarial vaccine is therefore feasible if modified peptides are suitably modified for an appropriate fit into the correct HLA-DRbeta1* molecule in order to form a proper MHC-II-peptide-TCR complex.

  7. Intrinsic Angular Momentum of Light.

    ERIC Educational Resources Information Center

    Santarelli, Vincent

    1979-01-01

    Derives a familiar torque-angular momentum theorem for the electromagnetic field, and includes the intrinsic torques exerted by the fields on the polarized medium. This inclusion leads to the expressions for the intrinsic angular momentum carried by the radiation traveling through a charge-free medium. (Author/MA)

  8. Targeting Plasticity with Vagus Nerve Stimulation to Treat Neurological Disease

    PubMed Central

    Hays, Seth A.; Rennaker, Robert L.; Kilgard, Michael P.

    2015-01-01

    Pathological neural activity in a variety of neurological disorders could be treated by directing plasticity to specifically renormalize aberrant neural circuits, thereby restoring normal function. Brief bursts of acetylcholine and norepinephrine can enhance the neural plasticity associated with coincident events. Vagus nerve stimulation (VNS) represents a safe and effective means to trigger the release of these neuromodulators with a high degree of temporal control. VNS-event pairing can generate highly specific and long-lasting plasticity in sensory and motor cortex. Based on the capacity to drive specific changes in neural circuitry, VNS paired with experience has been successful in effectively ameliorating animal models of chronic tinnitus, stroke, and posttraumatic stress disorder. Targeted plasticity therapy utilizing VNS is currently being translated to humans to treat chronic tinnitus and improve motor recovery after stroke. This chapter will discuss the current progress of VNS paired with experience to drive specific plasticity to treat these neurological disorders and will evaluate additional future applications of targeted plasticity therapy. PMID:24309259

  9. The effects of hormones and physical exercise on hippocampal structural plasticity.

    PubMed

    Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

    2016-04-01

    The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Development of intrinsic IPT scintillator

    SciTech Connect

    Bross, A.D.

    1989-07-31

    We report on the development of a new polystyrene based plastic scintillator. Optical absorption, fluorescence and light output measurements are presented. Preliminary results of radiation damage effects are also given and compared to the effects on a commercial plastic scintillator, NE 110. 6 refs., 12 figs.

  11. Review of the partitioning of chemicals into different plastics: Consequences for the risk assessment of marine plastic debris.

    PubMed

    O'Connor, Isabel A; Golsteijn, Laura; Hendriks, A Jan

    2016-12-15

    Marine plastic debris are found worldwide in oceans and coastal areas. They degrade only slowly and contain chemicals added during manufacture or absorbed from the seawater. Therefore, they can pose a long-lasting contaminant source and potentially transfer chemicals to marine organisms when ingested. In order to assess their risk, the contaminant concentration in the plastics needs to be estimated and differences understood. We collected from literature plastic water partition coefficients of various organic chemicals for seven plastic types: polydimethylsiloxane (PDMS), high-density, low-density and ultra-high molecular weight polyethylene (LDPE, HDPE, UHMWPE), polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC). Most data was available for PDMS (1060) and LDPE (220), but much less for the remaining plastics (73). Where possible, regression models were developed and the partitioning was compared between the different plastic types. The partitioning of chemicals follows the order of LDPE≈HDPE≥PP>PVC≈PS. Data describing the impact of weathering are urgently needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Recent progress on intrinsic charm

    NASA Astrophysics Data System (ADS)

    Hobbs, T. J.

    2017-03-01

    Over the past ˜10 years, the topic of the nucleon's nonperturbative or intrinsic charm (IC) content has enjoyed something of a renaissance, largely motivated by theoretical developments involving quark modelers and PDF-fitters. In this talk I will briefly describe the importance of intrinsic charm to various issues in high-energy phenomenology, and survey recent progress in constraining its overall normalization and contribution to the momentum sum rule of the nucleon. I end with the conclusion that progress on the side of calculation has now placed the onus on experiment to unambiguously resolve the proton's intrinsic charm component.

  13. Homeostatic role of heterosynaptic plasticity: models and experiments

    PubMed Central

    Chistiakova, Marina; Bannon, Nicholas M.; Chen, Jen-Yung; Bazhenov, Maxim; Volgushev, Maxim

    2015-01-01

    Homosynaptic Hebbian-type plasticity provides a cellular mechanism of learning and refinement of connectivity during development in a variety of biological systems. In this review we argue that a complimentary form of plasticity—heterosynaptic plasticity—represents a necessary cellular component for homeostatic regulation of synaptic weights and neuronal activity. The required properties of a homeostatic mechanism which acutely constrains the runaway dynamics imposed by Hebbian associative plasticity have been well-articulated by theoretical and modeling studies. Such mechanism(s) should robustly support the stability of operation of neuronal networks and synaptic competition, include changes at non-active synapses, and operate on a similar time scale to Hebbian-type plasticity. The experimentally observed properties of heterosynaptic plasticity have introduced it as a strong candidate to fulfill this homeostatic role. Subsequent modeling studies which incorporate heterosynaptic plasticity into model neurons with Hebbian synapses (utilizing an STDP learning rule) have confirmed its ability to robustly provide stability and competition. In contrast, properties of homeostatic synaptic scaling, which is triggered by extreme and long lasting (hours and days) changes of neuronal activity, do not fit two crucial requirements for a hypothetical homeostatic mechanism needed to provide stability of operation in the face of on-going synaptic changes driven by Hebbian-type learning rules. Both the trigger and the time scale of homeostatic synaptic scaling are fundamentally different from those of the Hebbian-type plasticity. We conclude that heterosynaptic plasticity, which is triggered by the same episodes of strong postsynaptic activity and operates on the same time scale as Hebbian-type associative plasticity, is ideally suited to serve a homeostatic role during on-going synaptic plasticity. PMID:26217218

  14. Long-lasting permethrin-impregnated clothing: protective efficacy against malaria in hyperendemic foci, and laundering, wearing, and weathering effects on residual bioactivity after worst-case use in the rain forests of French Guiana.

    PubMed

    Most, Bruno; Pommier de Santi, Vincent; Pagès, Frédéric; Mura, Marie; Uedelhoven, Waltraud M; Faulde, Michael K

    2017-02-01

    Personal protective measures against hematophagous vectors constitute the first line of defense against arthropod-borne diseases. However, guidelines for the standardized testing and licensing of insecticide-treated clothing are still lacking. The aim of this study was to analyze the preventive effect of long-lasting polymer-coated permethrin-impregnated clothing (PTBDU) against malaria after exposure to high-level disease transmission sites as well as the corresponding loss of permethrin and bioactivity during worst-case field use. Between August 2011 and June 2012, 25 personnel wearing PTBDUs and exposed for 9.5 person-months in hyperendemic malaria foci in the rain forest of French Guiana contracted no cases of malaria, whereas 125 persons wearing untreated uniforms only, exposed for 30.5 person-months, contracted 11 cases of malaria, indicating that PTBDU use significantly (p = 0.0139) protected against malaria infection. In the field, PTBDUs were laundered between 1 and 218 times (mean 25.2 ± 44.8). After field use, the mean remaining permethrin concentration in PTBDU fabric was 732.1 ± 321.1 min varying between 130 and 1270 mg/m 2 (mean 743.9 ± 304.2 mg/m 2 ) in blouses, and between 95 and 1290 mg/m 2 (mean 720.2 ± 336.9 mg/m 2 ) in trousers. Corresponding bioactivity, measured according to internal licensing conditions as KD 99 times against Aedes aegypti mosquitoes, varied between 27.5 and 142.5 min (mean 47.7 ± 22.1 min) for blouses, and between 25.0 and 360 min (mean 60.2 ± 66.1 min) for trousers. We strongly recommend the use of long-lasting permethrin-impregnated clothing for the prevention of mosquito-borne diseases, including chikungunya, dengue, and zika fevers, which are currently resurging globally.

  15. A household randomized, controlled trial of the efficacy of 0.03% transfluthrin coils alone and in combination with long-lasting insecticidal nets on the incidence of Plasmodium falciparum and Plasmodium vivax malaria in Western Yunnan Province, China.

    PubMed

    Hill, Nigel; Zhou, Hong Ning; Wang, Piyu; Guo, Xiaofang; Carneiro, Ilona; Moore, Sarah J

    2014-05-31

    Mosquito coils are the most commonly used household insecticidal product in the world with sales exceeding 50 billion coils, used by two billion people worldwide annually. Despite strong evidence that coils prevent mosquito bites a systematic review concluded that there is no evidence that burning mosquito coils prevents malaria acquisition. Therefore, the current trial was designed to measure and compare prevention of malaria infection by mosquito coils or long-lasting insecticidal net (LLIN) or a combination of the two in Yunnan, China in the Greater Mekong sub-region. A four-arm single blind household-randomized design was chosen as coils emanate insecticide throughout the household. Households enrolled at baseline were randomly allocated by the lottery method to one of the four intervention arms: (i) nothing, (ii) 0.03% transfluthrin coils alone, (iii) deltamethrin long-lasting insecticide treated nets, (LLINs) alone or (iv) a combination of transfluthrin coils and deltamethrin LLINs. All household members were recruited to the study, with only those households excluded with pregnant or breastfeeding mothers, members with chest complaints or allergies or members that regularly slept away from home. The main outcome of interest was Plasmodium falciparum malaria prevalence detected by rapid diagnostic tests (RDTs) during six repeated monthly cross-sectional surveys. The secondary outcome of interest was the effect on Plasmodium vivax prevalence detected in the same way. A total of 2,052 households were recruited into the study, comprising 7,341 individuals The odds ratios of testing positive by RDT with P. falciparum or P. vivax were >75% lower for all intervention arms compared with the control arm. Coils alone provided 77% protection (95% CI: 50%-89%), LLINs provided 91% protection (95% CI: 72%-97%) and the combination of coils and LLINs provided 94% protection (95% CI: 77%-99%) against P. falciparum compared with the control arm. There was no statistically

  16. Report on the second WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Geneva, Switzerland, 5-7 May 2014.

    PubMed

    Cox, Nancy J; Hickling, Julian; Jones, Rebecca; Rimmelzwaan, Guus F; Lambert, Linda C; Boslego, John; Rudenko, Larisa; Yeolekar, Leena; Robertson, James S; Hombach, Joachim; Ortiz, Justin R

    2015-11-27

    On 5-7 May 2014, the World Health Organization (WHO) convened the second integrated meeting on "influenza vaccines that induce broadly protective and long-lasting immune responses". Around 100 invited experts from academia, the vaccine industry, research and development funders, and regulatory and public health agencies attended the meeting. Areas covered included mechanisms of protection in natural influenza-virus infection and vaccine-induced immunity, new approaches to influenza-vaccine design and production, and novel routes of vaccine administration. A timely focus was on how this knowledge could be applied to both seasonal influenza and emerging viruses with pandemic potential such as influenza A (H7N9), currently circulating in China. Special attention was given to the development of possible universal influenza vaccines, given that the Global Vaccine Action Plan calls for at least one licensed universal influenza vaccine by 2020. This report highlights some of the topics discussed and provides an update on studies published since the report of the previous meeting. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

  17. To assess whether indoor residual spraying can provide additional protection against clinical malaria over current best practice of long-lasting insecticidal mosquito nets in The Gambia: study protocol for a two-armed cluster-randomised trial

    PubMed Central

    2011-01-01

    Background Recently, there has been mounting interest in scaling-up vector control against malaria in Africa. It needs to be determined if indoor residual spraying (IRS with DDT) will provide significant marginal protection against malaria over current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in a controlled trial, given that DDT is currently the most persistent insecticide for IRS. Methods A 2 armed cluster-randomised controlled trial will be conducted to assess whether DDT IRS and LLINs combined provide better protection against clinical malaria in children than LLINs alone in rural Gambia. Each cluster will be a village, or a group of small adjacent villages; all clusters will receive LLINs and half will receive IRS in addition. Study children, aged 6 months to 13 years, will be enrolled from all clusters and followed for clinical malaria using passive case detection to estimate malaria incidence for 2 malaria transmission seasons in 2010 and 2011. This will be the primary endpoint. Exposure to malaria parasites will be assessed using light and exit traps followed by detection of Anopheles gambiae species and sporozoite infection. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection and the prevalence of anaemia. Discussion Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. Trial Registration ISRCTN01738840 - Spraying And Nets Towards malaria Elimination (SANTE) PMID:21663656

  18. To assess whether indoor residual spraying can provide additional protection against clinical malaria over current best practice of long-lasting insecticidal mosquito nets in The Gambia: study protocol for a two-armed cluster-randomised trial.

    PubMed

    Pinder, Margaret; Jawara, Musa; Jarju, Lamin B S; Kandeh, Ballah; Jeffries, David; Lluberas, Manuel F; Mueller, Jenny; Parker, David; Bojang, Kalifa; Conway, David J; Lindsay, Steve W

    2011-06-10

    Recently, there has been mounting interest in scaling-up vector control against malaria in Africa. It needs to be determined if indoor residual spraying (IRS with DDT) will provide significant marginal protection against malaria over current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in a controlled trial, given that DDT is currently the most persistent insecticide for IRS. A 2 armed cluster-randomised controlled trial will be conducted to assess whether DDT IRS and LLINs combined provide better protection against clinical malaria in children than LLINs alone in rural Gambia. Each cluster will be a village, or a group of small adjacent villages; all clusters will receive LLINs and half will receive IRS in addition. Study children, aged 6 months to 13 years, will be enrolled from all clusters and followed for clinical malaria using passive case detection to estimate malaria incidence for 2 malaria transmission seasons in 2010 and 2011. This will be the primary endpoint. Exposure to malaria parasites will be assessed using light and exit traps followed by detection of Anopheles gambiae species and sporozoite infection. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection and the prevalence of anaemia. Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. ISRCTN01738840 - Spraying And Nets Towards malaria Elimination (SANTE).

  19. Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports.

    PubMed

    Imaoka, Yuki; Kuranishi, Fumito; Miyazaki, Tsubasa; Yasuda, Hiroko; Ohno, Tadao

    2017-09-11

    The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.

  20. Residual activity and integrity of PermaNet® 2.0 after 24 months of household use in a community randomised trial of long lasting insecticidal nets against visceral leishmaniasis in India and Nepal.

    PubMed

    Picado, Albert; Singh, Shri Prakash; Vanlerberghe, Veerle; Uranw, Surendra; Ostyn, Bart; Kaur, Harparkash; Das, Murari Lal; Sundar, Shyam; Rijal, Suman; Tungu, Patrick; Boelaert, Marleen; Rowland, Mark

    2012-03-01

    The World Health Organization (WHO) recommends several brands of long lasting insecticidal net (LN) for protection against insect vectors but also advises national programmes to monitor and evaluate performance under local conditions to help them select the most suitable LN for their setting. During the course of a community randomised trial of LNs against visceral leishmaniasis in northern India and Nepal, opportunity arose to assess the efficacy of PermaNet 2.0 (Vestergaard-Frandsen, Denmark) after two years of use against sandfly vectors. Between 63% (India) and 78% (Nepal) of LNs became holed over the course of two years, deltamethrin residues fell from 55 mg/m(2) to an average of 11.6 mg/m(2) (India) and 27.9 mg/m(2) (Nepal), but on the basis of bioassay criteria all LNs tested still met the WHO Pesticide Evaluation Scheme standard for LN effectiveness. Nets had on average only been washed 2.5 times (India) and 0.6 times (Nepal) by householders over the course of two years. The loss of insecticide was attributed to factors which had little or nothing to do with washing, such as handling, friction and torsion during daily use. Under conditions pertaining in this region of south Asia, and for two years at least, this brand of net continues to meet the criteria established by WHO for LNs. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  1. Cell biology in neuroscience: the interplay between Hebbian and homeostatic synaptic plasticity.

    PubMed

    Vitureira, Nathalia; Goda, Yukiko

    2013-10-28

    Synaptic plasticity, a change in the efficacy of synaptic signaling, is a key property of synaptic communication that is vital to many brain functions. Hebbian forms of long-lasting synaptic plasticity-long-term potentiation (LTP) and long-term depression (LTD)-have been well studied and are considered to be the cellular basis for particular types of memory. Recently, homeostatic synaptic plasticity, a compensatory form of synaptic strength change, has attracted attention as a cellular mechanism that counteracts changes brought about by LTP and LTD to help stabilize neuronal network activity. New findings on the cellular mechanisms and molecular players of the two forms of plasticity are uncovering the interplay between them in individual neurons.

  2. Brain plasticity and sleep: Implication for movement disorders.

    PubMed

    Caverzasio, Serena; Amato, Ninfa; Manconi, Mauro; Prosperetti, Chiara; Kaelin-Lang, Alain; Hutchison, William Duncan; Galati, Salvatore

    2018-03-01

    Brain plasticity is a lifelong process and involves both Hebbian and non-Hebbian synaptic plasticity. The latter, such as intrinsic plasticity and homeostatic synaptic plasticity or synaptic scaling, is thought to counteract Hebbian plasticity, in order to maintain a balanced network. Recent studies support the role of sleep in the regulation of homeostatic synaptic plasticity involved in memory and learning processes. Most evidence focus on the dependence of memory and plasticity in sleep mechanisms. Abnormal brain plasticity during sleep might be implicated in the development of movement disorders, particularly Parkinson's disease (PD) and dystonia. From that, the great interest to understand the underlying process of sleep in relation to movement disorders. The first objective of the review is to summarize the latest knowledge about brain plasticity. The second objective is to analyze the association between sleep, memory and brain plasticity. Finally, the review aims to assess the consequence of abnormal plasticity during PD and dystonia with a viewpoint on the underling pathogenesis of these disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Early life nutrition and neural plasticity

    PubMed Central

    Georgieff, Michael K.; Brunette, Katya E; Tran, Phu V

    2015-01-01

    The human brain undergoes a remarkable transformation during fetal life and the first postnatal years from a relatively undifferentiated but pluripotent organ to a highly specified and organized one. The outcome of this developmental maturation is highly dependent on a sequence of environmental exposures that can have either positive or negative influences on the ultimate plasticity of the adult brain. Many environmental exposures are beyond the control of the individual, but nutrition is not. An ever-increasing amount of research demonstrates that nutrition not only shapes the brain and affects its function during development, but that several nutrients early in life have profound and long-lasting effects on the brain. Nutrients have been shown to alter opening and closing of critical and sensitive periods of particular brain regions. This paper discusses the roles that various nutrients play in shaping the developing brain, concentrating specifically on recently explicated biological mechanisms by which particularly salient nutrients influence childhood and adult neural plasticity. PMID:25997762

  4. Unusual biophysics of intrinsically disordered proteins.

    PubMed

    Uversky, Vladimir N

    2013-05-01

    Research of a past decade and a half leaves no doubt that complete understanding of protein functionality requires close consideration of the fact that many functional proteins do not have well-folded structures. These intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered protein regions (IDPRs) are highly abundant in nature and play a number of crucial roles in a living cell. Their functions, which are typically associated with a wide range of intermolecular interactions where IDPs possess remarkable binding promiscuity, complement functional repertoire of ordered proteins. All this requires a close attention to the peculiarities of biophysics of these proteins. In this review, some key biophysical features of IDPs are covered. In addition to the peculiar sequence characteristics of IDPs these biophysical features include sequential, structural, and spatiotemporal heterogeneity of IDPs; their rough and relatively flat energy landscapes; their ability to undergo both induced folding and induced unfolding; the ability to interact specifically with structurally unrelated partners; the ability to gain different structures at binding to different partners; and the ability to keep essential amount of disorder even in the bound form. IDPs are also characterized by the "turned-out" response to the changes in their environment, where they gain some structure under conditions resulting in denaturation or even unfolding of ordered proteins. It is proposed that the heterogeneous spatiotemporal structure of IDPs/IDPRs can be described as a set of foldons, inducible foldons, semi-foldons, non-foldons, and unfoldons. They may lose their function when folded, and activation of some IDPs is associated with the awaking of the dormant disorder. It is possible that IDPs represent the "edge of chaos" systems which operate in a region between order and complete randomness or chaos, where the complexity is maximal. This article is part of a Special Issue

  5. Providing plastic zone extrusion

    SciTech Connect

    Manchiraju, Venkata Kiran; Feng, Zhili; David, Stan A.

    2017-04-11

    Plastic zone extrusion may be provided. First, a compressor may generate frictional heat in stock to place the stock in a plastic zone of the stock. Then, a conveyer may receive the stock in its plastic zone from the compressor and transport the stock in its plastic zone from the compressor. Next, a die may receive the stock in its plastic zone from the conveyer and extrude the stock to form a wire.

  6. Intrinsically irreversible thermoacoustic heat engine

    SciTech Connect

    Wheatley, J.; Hofler, T.; Swift, G.W.; Migliori, A.

    1983-07-01

    Certain thermoacoustic effects are described which form the basis for a heat engine that is intrinsically irreversible in the sense that it requires thermal lags for its operation. After discussing several acoustical heating and cooling effects, including the behavior of a new structure called a ''thermoacoustic couple,'' we discuss structures that can be placed in acoustically resonant tubes to produce both substantial heat pumping effects and, for restricted heat inputs, large temperature differences. The results are analyzed quantitatively using a second-order thermoacoustic theory based on the work of Rott. The qualities of the acoustic engine are generalized to describe a class of intrinsically irreversible heat engines of which the present acoustic engine is a special case. Finally the results of analysis of several idealized intrinsically irreversible engines are presented. These suggest that the efficiency of such engines may be determined primarily by geometry or configuration rather than by temperature.

  7. Intrinsic Transparent Conductors without Doping.

    PubMed

    Zhang, Xiuwen; Zhang, Lijun; Perkins, John D; Zunger, Alex

    2015-10-23

    Transparent conductors (TCs) combine the usually contraindicated properties of electrical conductivity with optical transparency and are generally made by starting with a transparent insulator and making it conductive via heavy doping, an approach that generally faces severe "doping bottlenecks." We propose a different idea for TC design-starting with a metallic conductor and designing transparency by control of intrinsic interband transitions and intraband plasmonic frequency. We identify the specific design principles for three such prototypical intrinsic TC classes and then search computationally for materials that satisfy them. Remarkably, one of the intrinsic TC, Ag(3)Al(22)O(34), is predicted also to be a prototype 3D compounds that manifest natural 2D electron gas regions with very high electron density and conductivity.

  8. Intrinsic top-down unmanufacturability.

    PubMed

    Kelly, M J

    2011-06-17

    Although small structures can be fabricated by deposition, lithography and etching, in some cases their intrinsic variability precludes their use as elements in useful arrays. Manufacture is a proper subset of fabrication. We show that structures with 3 nm design rules can be fabricated but not manufactured in a top-down approach-they do not have the reproducibility to give a satisfactory yield to a pre-ordained specification. It is also shown that the transition from manufacturability to intrinsic unmanufacturability takes place at nearer 7 nm design rules.

  9. Novel long-lasting impregnation technique transferred from clothing to bednets: extended efficacy and residual activity of different pyrethroids against Aedes aegypti as shown by EN ISO 6330-standardized machine laundering.

    PubMed

    Faulde, Michael; Albiez, Gunther; Nehring, Oliver

    2012-06-01

    A novel long-lasting insecticide-treated net (LLIN) has been designed by embedding the pyrethroids deltamethrin, cyfluthrin, permethrin, or etofenprox, onto the fibres of bed net cotton fabric by transferring a new polymer-coating technique from clothing to netting material. EN ISO 6330, the more stringent European Norm for domestic washing and drying procedures for textile testing, has been newly employed to monitor and validate more precise wash durability and residual bioactivity of LLINs. Wash durability, residual insecticidal activity and mosquito landing/biting protection has been investigated and compared with four commercially available LLINs. The pyrethroid-embedding impregnation technique allows binding of high concentrations exceeding 8,000 mg permethrin/m(2) within one single-polymer layer. Recovery rates of 95.7 ± 5.8%, 92.4 ± 14.0%, 70.2 ± 9.1%, and 64.2 ± 6.3% for cyfluthrin; 32.4 ± 11.4%, 32.4 ± 12%, 35.1 ± 16.2%, and 35.8 ± 15.7% for deltamethrin; 75.3 ± 12.9%, 57.1 ± 15.8%, 48.5 ± 4.0%, and 35.6 ± 4.7% for etofenprox; and 95.7 ± 5.8%, 80.2 ± 8.6%, 39.1 ± 7.9%, and 34.1 ± 8.8% were measured after 1, 5, 10, and 20 launderings. Laundering resistance was highest with cyfluthrin > deltamethrin ≈ etofenprox ≈ permethrin. After one and five launderings, commercial LLINs revealed percentage pyrethroid recovery rates of 26.3 ± 11.8% and 0.9 ± 1.2% for the Care Plus(®) net; 31.8% and 28.9% for the Permanet(®) 2.0; 61.4% and 45.6% for the Net Protect(®); and 80.4% and 68.3% for the Conmanet(®). Recovery rates reveal that the polymer-coating method resulted in extended wash durability. Dose-dependent 100% knockdown rates were most effective with deltamethrin > cyfluthrin > permethrin ≈ etofenprox. LLINs tested at concentrations up to 8,000 mg permethrin/m(2) did not protect from mosquito bites. Results on long-lasting efficacy and

  10. Deriving the properties of coronal pressure fronts in 3-D: particle acceleration, time dependent magnetic connectivity with solar surface and link with long lasting gamma ray emission in three far side Coronal Mass Ejections

    NASA Astrophysics Data System (ADS)

    Plotnikov, I.; Rouillard, A.

    2016-12-01

    Identifying the physical mechanisms that produce the most energetic particles is a long-standing observational and theoretical challenge in astrophysics. Strong pressure waves have been proposed as efficient accelerators both in the solar and astrophysical contexts via various mechanisms such as diffusive-shock/shock-drift acceleration and betatron effects. In diffusive-shock acceleration, the efficacy of the process relies on shock waves being super-critical or moving several times faster than the characteristic speed of the medium they propagate through (a high Alfven Mach number). High-cadence, multipoint imaging now permits the 3-D reconstruction of pressure waves formed during the eruption of coronal mass ejections. Using these unprecedented capabilities, some recent studies have provided new insights on the timing and longitudinal extent of solar energetic particles, including the first derivations of the time-dependent 3-dimensional distribution of the expansion speed and Mach numbers of coronal shock waves. These new techniques also provide the opportunity to investigate the enigmatic long-duration gamma ray events. We study three far side Coronal Mass Ejection with an associated gamma-ray emission. Using the shock time-dependent reconstruction and observationnaly based MHD simulation models / PFSS field reconstruction, we derive the magnetic connectivity of the shock with solar surface. The fast shock - high Mach number regions of the shock are found to be rapidly connected with the visible solar surface. Energetic particle measurements by spacecrafts at different longitudes show that these events are efficient particle accelerators for protons above 100 MeV (possible several GeVs). These observations provide an empirical evidence that at least a part of long lasting gamma ray emission may result from shock accelerated particles.

  11. Effectiveness of post-campaign, door-to-door, hang-up, and communication interventions to increase long-lasting, insecticidal bed net utilization in Togo (2011-2012): a cluster randomized, control trial.

    PubMed

    Desrochers, Rachelle E; Siekmans, Kendra; Berti, Peter R; Bramhill, Karen; Buchan, Sarah A W; Battah, Guy K; Gbetoglo, Dodji; Vignikin, Kokou; Sabino, Alice

    2014-07-09

    It is well established that insecticide-treated bed nets (ITNs), in particular long-lasting, insecticidal nets (LLINs), can be used as one of the primary interventions for effective malaria control. A consistent gap between net ownership and use has been observed, indicating that factors exist that prevent an owned mosquito net from being used. One approach used in the context of LLIN campaigns is a post-distribution, door-to-door visit of households with educational messages and to physically assist with hang-up of nets. A cluster randomized trial was conducted in the Plateaux Region of Togo to evaluate the effectiveness of different approaches to post-LLIN campaign home visits (number of visits and timing) by volunteers to enhance LLIN hang-up and utilization. It was found that, in general, households that received intervention visits, particularly the most recent intervention visit, had levels of use that were typically 5 to 10% higher than the control households, while access did not differ among control and intervention households. Eight months post-campaign, ITN use by all individuals, children under five years and women of reproductive age was 11.3 to 14.4 percentage points greater in the study arm that received all three intervention visits than in the control communities. In households that received one or two additional door-to-door visits, the majority of respondents indicated that the volunteer provided new information during the visit regarding the use and importance of ITNs despite having received previous multiple visits. The impact of the interventions appears to have been primarily through the delivery and reinforcement of key behaviour-change communication (BCC) messages regarding the importance of using an ITN and its care. Regardless of whether the respondents in fact received new information or had forgotten earlier information, this suggests that regular visits from community agents are useful in reinforcing key BCC messages.

  12. The implementation of long-lasting insecticidal bed nets has differential effects on the genetic structure of the African malaria vectors in the Anopheles gambiae complex in Dielmo, Senegal.

    PubMed

    Sougoufara, Seynabou; Sokhna, Cheikh; Diagne, Nafissatou; Doucouré, Souleymane; Sembène, Pape MBacké; Harry, Myriam

    2017-08-15

    Mosquitoes belonging to the Anopheles gambiae complex are the main vectors of malaria in sub-Saharan Africa. Among these, An. gambiae, Anopheles coluzzii and Anopheles arabiensis are the most efficient vectors and are largely distributed in sympatric locations. However, these species present ecological and behavioural differences that impact their vectorial capacity and complicate vector-control efforts, mainly based on long-lasting insecticidal bed nets (LLINs) and indoor residual spraying (IRS). In this study, the genetic structure of these three species in a Senegalese village (Dielmo) was investigated using microsatellite data in samples collected in 2006 before implementation of LLINs, in 2008, when they were introduced, and in 2010, 2 years after the use of LLINs. In this study 611 individuals were included, namely 136 An. coluzzii, 101 An. gambiae, 6 An. coluzzii/An. gambiae hybrids and 368 An. arabiensis. According to the species, the effect of the implementation of LLINs in Dielmo is differentiated. Populations of the sister species An. coluzzii and An. gambiae regularly experienced bottleneck events, but without significant inbreeding. The Fst values suggested in 2006 a breakdown of assortative mating resulting in hybrids, but the introduction of LLINs was followed by a decrease in the number of hybrids. This suggests a decrease in mating success of hybrids, ecological maladaptation, or a lesser probability of mating between species due to a decrease in An. coluzzii population size. By contrast, the introduction of LLINs has favoured the sibling species An. arabiensis. In this study, some spatial and temporal structuration between An. arabiensis populations were detected, especially in 2008, and the higher genetic diversity observed could result from a diversifying selection. This work demonstrates the complexity of the malaria context and shows the need to study the genetic structure of Anopheles populations to evaluate the effectiveness of vector

  13. Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

    PubMed

    Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2014-10-07

    Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Targeting the genital tract mucosa with a lipopeptide/recombinant adenovirus prime/boost vaccine induces potent and long-lasting CD8+ T cell immunity against herpes: importance of MyD88.

    PubMed

    Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; Benmohamed, Lbachir

    2012-11-01

    Targeting of the mucosal immune system of the genital tract with subunit vaccines has failed to induce potent and durable local CD8(+) T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), which causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8(+) T cell immunity to protect the female genital tract from herpes. The lipopeptide vaccine and the rAdv5 vaccine express the immunodominant HSV-2 CD8(+) T cell epitope (gB(498-505)), and both were delivered intravaginally in the progesterone-induced B6 mouse model of genital herpes. Compared with mice immunized with the homologous lipopeptide/lipopeptide (Lipo/Lipo) vaccine, the Lipo/rAdv5 prime/boost immunized mice 1) developed potent and sustained HSV-specific CD8(+) T cells, detected in both the genital tract draining nodes and in the vaginal mucosa; 2) had significantly lower virus titers; 3) had decreased overt signs of genital herpes disease; and 4) did not succumb to lethal infection (p < 0.005) after intravaginal HSV-2 challenge. Polyfunctional CD8(+) T cells, producing IFN-γ, TNF-α, and IL-2 and exhibiting cytotoxic activity, were associated with protection (p < 0.005). The protective CD8(+) T cell response was significantly compromised in the absence of the adapter MyD88 (p = 0.0001). Taken together, these findings indicate that targeting of the vaginal mucosa with a Lipo/rAdv5 prime/boost vaccine elicits a potent, MyD88-dependent, and long-lasting mucosal CD8(+) T cell protective immunity against sexually transmitted herpes infection and disease.

  15. Targeting the Genital Tract Mucosa with a Lipopeptide/Recombinant Adenovirus Prime/Boost Vaccine Induces Potent and Long-Lasting CD8+ T Cell Immunity Against Herpes: Importance of Myeloid Differentiation Factor 881

    PubMed Central

    Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; BenMohamed, Lbachir

    2012-01-01

    Targeting the mucosal immune system of the genital tract (GT) with subunit vaccines failed to induce potent and durable local CD8+ T cell immunity, crucial for protection against many sexually transmitted viral (STV) pathogens, including herpes simplex virus type 2 (HSV-2) that causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8+ T cell immunity to protect the female genital tract from herpes. The lipopeptide and the rAdv5 vaccine express the immunodominant HSV-2 CD8+ T cell epitope (gB498-505) and both were delivered intravaginally (IVAG) in the progesterone-induced B6 mouse model of genital herpes. Compared to its homologous lipopeptide/lipopeptide (Lipo/Lipo); the Lipo/rAdv5 prime/boost immunized mice: (i) developed potent and sustained HSV-specific CD8+ T cells, detected in both the GT draining nodes (GT-DLN) and in the vaginal mucosa (VM); (ii) had significantly lower virus titers; (iii) had decreased overt signs of genital herpes disease; and (iv) did not succumb to lethal infection (p < 0.005), following intravaginal HSV-2 challenge. Polyfunctional CD8+ T cells, producing IFN-γ, TNF-α and IL-2 and exhibiting cytotoxic activity, were associated with protection (p < 0.005). The protective CD8+ T cell response was significantly compromised in the absence of the adaptor myeloid differentiation factor 88 (MyD88) (p = 0.0001). Taken together, these findings indicate that targeting the VM with a Lipo/rAdv5 prime/boost vaccine elicits a potent, MyD88-dependent, and long-lasting mucosal CD8+ T cell protective immunity against sexually transmitted herpes infection and disease. PMID:23018456

  16. Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex.

    PubMed

    Bolzoni, Francesco; Esposti, Roberto; Bruttini, Carlo; Zenoni, Giuseppe; Jankowska, Elzbieta; Cavallari, Paolo

    2017-11-01

    Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Investigating the acceptability of non-mesh, long-lasting insecticidal nets amongst nomadic communities in Garissa County, Kenya using a prospective, longitudinal study design and cross-sectional household surveys.

    PubMed

    Gore-Langton, Georgia R; Mungai, James; Alenwi, Nfornuh; Abagira, Abdulla; Bicknell, Owen M; Harrison, Rebecca; Hassan, Farah A; Munga, Stephen; Njoroge, Francis; Juma, Elizabeth; Allan, Richard

    2015-02-05

    North East Kenya is an area of semi-arid terrain, prone to malaria epidemics. The distribution of long-lasting insecticidal nets (LLINs) has long been a key malaria intervention, however, for nomadic populations who live and sleep outside, in harsh climates and areas with increasing reports of exophagic behaviour of mosquitoes, traditional LLINs are often inadequate. This study investigates the acceptability of non-mesh LLINs, specifically designed to suit nomadic, outdoor sleeping communities. In September 2011, 13,922 non-mesh LLINs were distributed to 8,511 nomadic households in Garissa County, North East Province, Kenya. A prospective, longitudinal study design was used to assess the acceptability of this novel type of LLIN. Cross-sectional household surveys, focus group discussions (FGDs), and key informant interviews (KIs) were used to collect data on attitudes and practices regarding the Dumuria nets. A very high level of acceptability was reported with 95.3% of respondents stating they liked the nets. Of the factors reportedly determining net use the most frequently mentioned was "vulnerability". Of those with concerns about the nets, the colour (white) was the most frequently reported. The tailoring of LLINs to specific communities and contexts leads to increased levels of acceptability. Large-scale, blanket net distribution campaigns, which are currently the standard practice, do not cater for the specific and nuanced needs of the differing communities they often serve. This non-mesh LLIN offers a highly effective and desirable malaria prevention option to a typically hard to reach and underserved nomadic population at increased risk of malaria infection.

  18. Structural synaptic plasticity in the hippocampus induced by spatial experience and its implications in information processing.

    PubMed

    Carasatorre, M; Ramírez-Amaya, V; Díaz Cintra, S

    2016-10-01

    Long-lasting memory formation requires that groups of neurons processing new information develop the ability to reproduce the patterns of neural activity acquired by experience. Changes in synaptic efficiency let neurons organise to form ensembles that repeat certain activity patterns again and again. Among other changes in synaptic plasticity, structural modifications tend to be long-lasting which suggests that they underlie long-term memory. There is a large body of evidence supporting that experience promotes changes in the synaptic structure, particularly in the hippocampus. Structural changes to the hippocampus may be functionally implicated in stabilising acquired memories and encoding new information. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. NMR contributions to structural dynamics studies of intrinsically disordered proteins☆

    PubMed Central

    Konrat, Robert

    2014-01-01

    Intrinsically disordered proteins (IDPs) are characterized by substantial conformational plasticity. Given their inherent structural flexibility X-ray crystallography is not applicable to study these proteins. In contrast, NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This article will summarize key advances in basic physical-chemistry and NMR methodology, outline their limitations and envision future R&D directions. PMID:24656082

  20. NMR contributions to structural dynamics studies of intrinsically disordered proteins.

    PubMed

    Konrat, Robert

    2014-04-01

    Intrinsically disordered proteins (IDPs) are characterized by substantial conformational plasticity. Given their inherent structural flexibility X-ray crystallography is not applicable to study these proteins. In contrast, NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This article will summarize key advances in basic physical-chemistry and NMR methodology, outline their limitations and envision future R&D directions. Copyright © 2013 The Author. Published by Elsevier Inc. All rights reserved.

  1. Intrinsic Motivation in Physical Education

    ERIC Educational Resources Information Center

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  2. Intrinsic Rewards in School Crime.

    ERIC Educational Resources Information Center

    Csikszentmihalyi, Mihaly; Larson, Reed

    One of 52 theoretical papers on school crime and its relation to poverty, this chapter deals with the intrinsic motivation that the systemic structure of a school provides for opportunities for both prosocial and antisocial behavior. On the basis of previous research, the authors propose that the state of enjoyment occurs when a person is…

  3. Reading: Intrinsic versus Extrinsic Motivation.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Much debate centers on motivating student in reading achievement. Should students feel motivated from within (intrinsic motivation), or is it better to have extrinsic motivation whereby external stimuli are used to help learners achieve optimally in reading? This paper aims to analyze the two points of view about motivating students in reading…

  4. Evaluation of the efficacy of DDT indoor residual spraying and long-lasting insecticidal nets against insecticide resistant populations of Anopheles arabiensis Patton (Diptera: Culicidae) from Ethiopia using experimental huts

    PubMed Central

    2014-01-01

    Background Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal nets (LLINs) are major malaria vector control tools in Ethiopia. However, recent reports from different parts of the country showed that populations of Anopheles arabiensis, the principal malaria vector, have developed resistance to most families of insecticides recommended for public health use which may compromise the efficacy of both of these key vector control interventions. Thus, this study evaluated the efficacy of DDT IRS and LLINs against resistant populations of An. arabiensis using experimental huts in Asendabo area, southwestern Ethiopia. Methods The susceptibility status of populations of An. arabiensis was assessed using WHO test kits to DDT, deltamethrin, malathion, lambda-cyhalothrin, fenitrothion and bendiocarb. The efficacy of LLIN (PermaNet® 2.0), was evaluated using the WHO cone bioassay. Moreover, the effect of the observed resistance against malaria vector control interventions (DDT IRS and LLINs) were assessed using experimental huts. Results The findings of this study revealed that populations of An. arabiensis were resistant to DDT, deltamethrin, lambda-cyhalothrin and malathion with mortality rates of 1.3%, 18.8%, 36.3% and 72.5%, respectively but susceptible to fenitrothion and bendiocarb with mortality rates of 98.81% and 97.5%, respectively. The bio-efficacy test of LLIN (PermaNet® 2.0) against An. arabiensis revealed that the mosquito population showed moderate knockdown (64%) and mortality (78%). Moreover, mosquito mortalities in DDT sprayed huts and in huts with LLINs were not significantly different (p > 0.05) from their respective controls. Conclusion The evaluation of the efficacy of DDT IRS and LLINs using experimental huts showed that both vector control tools had only low to moderate efficacy against An. arabiensis populations from Ethiopia. Despite DDT being replaced by carbamates for IRS, the low efficacy of LLINs against the resistant population of An

  5. Mechanisms of Action of Escapin, a Bactericidal Agent in the Ink Secretion of the Sea Hare Aplysia californica: Rapid and Long-Lasting DNA Condensation and Involvement of the OxyR-Regulated Oxidative Stress Pathway

    PubMed Central

    Ko, Ko-Chun; Tai, Phang C.

    2012-01-01

    The marine snail Aplysia californica produces escapin, an l-amino acid oxidase, in its defensive ink. Escapin uses l-lysine to produce diverse products called escapin intermediate products of l-lysine (EIP-K), including α-amino-ε-caproic acid, Δ1-piperidine-2-carboxylic acid, and Δ2-piperidine-2-carboxylic acid. EIP-K and H2O2 together, but neither alone, is a powerful bactericide. Here, we report bactericidal mechanisms of escapin products on Escherichia coli. We show that EIP-K and H2O2 together cause rapid and long-lasting DNA condensation: 2-min treatment causes significant DNA condensation and killing, and 10-min treatment causes maximal effect, lasting at least 70 h. We isolated two mutants resistant to EIP-K plus H2O2, both having a single missense mutation in the oxidation regulatory gene, oxyR. A complementation assay showed that the mutated gene, oxyR(A233V), renders resistance to EIP-K plus H2O2, and a gene dosage effect leads to reduction of resistance for strains carrying wild-type oxyR. Temperature stress with EIP-K does not produce the bactericidal effect, suggesting the effect is due to a specific response to oxidative stress. The null mutant for any single DNA-binding protein—Dps, H-NS, Hup, Him, or MukB—was not resistant to EIP-K plus H2O2, suggesting that no single DNA-binding protein is necessary to mediate this bactericidal effect, but allowing for the possibility that EIP-K plus H2O2 could function through a combination of DNA-binding proteins. The bactericidal effect of EIP-K plus H2O2 was eliminated by the ferrous ion chelator 1,10-phenanthroline, and it was reduced by the hydroxyl radical scavenger thiourea, suggesting hydroxyl radicals mediate the effects of EIP-K plus H2O2. PMID:22232273

  6. Comparative field evaluation of combinations of long-lasting insecticide treated nets and indoor residual spraying, relative to either method alone, for malaria prevention in an area where the main vector is Anopheles arabiensis

    PubMed Central

    2013-01-01

    Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Methods Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. Results All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Conclusions Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In

  7. Comparative field evaluation of combinations of long-lasting insecticide treated nets and indoor residual spraying, relative to either method alone, for malaria prevention in an area where the main vector is Anopheles arabiensis.

    PubMed

    Okumu, Fredros O; Mbeyela, Edgar; Lingamba, Godfrey; Moore, Jason; Ntamatungiro, Alex J; Kavishe, Deo R; Kenward, Michael G; Turner, Elizabeth; Lorenz, Lena M; Moore, Sarah J

    2013-02-22

    Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS

  8. A cross-sectional study assessing the residual bio-efficacy and durability of field-distributed long-lasting insecticidal nets in malaria endemic ethnic communities of Assam, Northeast India.

    PubMed

    Dev, Vas; Barman, Keshab; Khound, Kamal

    2016-01-01

    Long-lasting insecticidal nets (LLINs) are being promoted for malaria vector control in the northeastern Indian state of Assam. A cross-sectional study was conducted to assess the current residual bio-efficacy and durability of both the Olyset(®) and PermaNet(®)2.0 LLINs that were distributed earlier in 2009, 2011 and 2013 to help formulate informed policy regarding net procurement, supplies and replacement. The study was undertaken in three different malaria endemic blocks of Assam during the period of June to October of 2014. The residual bio-efficacies were ascertained using the WHO cone-bioassay method for mosquito mortality post-exposure and corroborated with the ring-net assay for the median knockdown times of both types of LLINs in use by these communities. Cross-sectional community surveys were distributed to assess net ownership, utilization, community practices and the physical conditions of the nets in terms of being torn and the numbers of holes per position. Both the Olyset(®) and PermaNet(®)2.0 LLINs that were distributed in 2009 (i.e., nearly after five years of community usage) were completely torn, worn out and obsolete. However, the LLINs distributed in 2011 (i.e., three years of community usage) retained their residual bio-efficacies in susceptibility ranges that varied from 57% to 79%. However, for the LLINs that were distributed in 2013, the observed residual efficacy was adequate and resulted in a mosquito mortality rate >80 percent. Of the two types of LLINs inspected, the Olyset(®)nets were more durable and robust in terms of being torn less frequently (37.1%, 39/105) compared with the PermaNet(®)2.0 nets (51.8%, 204/394). Regarding the LLINs that were distributed in 2013, all were physically intact and in good condition. The majority of the distributed LLINs (99.2%, 639/644) were still in the possession of the householders of the surveyed populations. This study revealed that the serviceable life of the nets was slightly less than

  9. A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    PubMed

    Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

    2016-02-01

    Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Plastic casting resin poisoning

    MedlinePlus

    Epoxy poisoning; Resin poisoning ... Epoxy and resin can be poisonous if they are swallowed or their fumes are breathed in. ... Plastic casting resins are found in various plastic casting resin products.

  11. Plastic encapsulated parts

    SciTech Connect

    Castillo, T.

    1994-10-01

    Plastic semiconductor packages were characterized as possible alternatives for canned devices, which are susceptible to internal shorts caused by conductive particles. Highly accelerated stress testing (HAST) as well as electrical and mechanical testing were conducted on plastic technology devices.

  12. #PlasticSurgery.

    PubMed

    Branford, Olivier A; Kamali, Parisa; Rohrich, Rod J; Song, David H; Mallucci, Patrick; Liu, Daniel Z; Lang, Dustin; Sun, Kristi; Stubican, Miran; Lin, Samuel J

    2016-12-01

    Social media use is growing inexorably, and there is public appetite for evidence-based information. Little is known about engagement by plastic surgeons with social media. The aim of this study was to examine posting about plastic surgery on Twitter, to best inform how board-certified plastic surgeons could use the hashtag #PlasticSurgery as a tool to educate patients and the public. A prospective analysis of 2880 "tweets" containing the words "plastic surgery" was performed. The following were assessed: identity of author, use of the hashtag #PlasticSurgery, subject matter, whether link to study was provided, and whether posts by surgeons were self-promotional or educational. Social media posting about plastic surgery is dominated by the public, accounting for 70.6 percent of posts versus only 6.0 percent by plastic surgeons. Only 5.4 percent of all tweets contained the hashtag #PlasticSurgery, although almost half of those that did were by plastic surgeons. Of these, 61.3 percent of posts by plastic surgeons were about aesthetic surgery; additional posts were about basic science, patient safety, and reconstruction (13.9, 4.0, and 2.3 percent, respectively). Eighteen scientific articles were referenced, with a link to the Journal site posted in two tweets. Of posts by plastic surgeons, 37.0 percent were self-promotional. The American Society of Plastic Surgeons and its Journal have recognized that social media may be used to educate and engage. Board-certified plastic surgeons have a great opportunity to promote evidence-based plastic practice by means of #PlasticSurgery in the interests of supporting patients and the profession.

  13. Plastics in Building.

    ERIC Educational Resources Information Center

    Skeist, Irving, Ed.

    The evaluation and use of plastics in the construction industry are explained. The contributors offer extensive, timely, and thoroughly researched data on the chemistry, properties, functions, engineering behavior, and specific applications of plastics to building requirements. The major subjects discussed in depth are--(1) the role of plastics in…

  14. Tomorrow's Plastic World

    ERIC Educational Resources Information Center

    Macdonald, Averil

    2005-01-01

    Far from being just cheap packaging materials, plastics may be the materials of tomorrow. Plastic can conduct electricity, and this opens up a host of high-tech possibilities in the home and in energy generation. These possibilities are discussed here along with how plastic can be recycled and perhaps even grown.

  15. Processing of plastics

    PubMed Central

    Spaak, Albert

    1975-01-01

    An overview is given of the processing of plastic materials from the handling of polymers in the pellet and powder form to manufacturing of a plastic fabricated product. Various types of equipment used and melt processing ranges of various polymer formulations to make the myriad of plastic products that are commercially available are discussed. PMID:1175556

  16. Intrinsic Patterns of Human Activity

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  17. Biodegradability of Plastics

    PubMed Central

    Tokiwa, Yutaka; Calabia, Buenaventurada P.; Ugwu, Charles U.; Aiba, Seiichi

    2009-01-01

    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed. PMID:19865515

  18. Preparing, Characterizing, and Investigating Luminescent Properties of a Series of Long-Lasting Phosphors in a SrO-Al[subscript 2]O[subscript 3] System: An Integrated and Inquiry-Based Experiment in Solid State Chemistry for the Undergraduate Laboratory

    ERIC Educational Resources Information Center

    Ma, Yan-Zi; Jia, Li; Ma, Kai-Guo; Wang, Hai-Hong; Jing, Xi-Ping

    2017-01-01

    An integrated and inquiry-based experiment on solid state chemistry is applied to an inorganic chemistry lab course to provide insight into the characteristics of the solid phase reaction. In this experiment, students have the opportunity to synthesize long-lasting phosphors with formula xSrO·yAl[subscript 2]O[subscript 3]:Eu[superscript 2+],…

  19. Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons.

    PubMed

    Jędrzejewska-Szmek, Joanna; Damodaran, Sriraman; Dorman, Daniel B; Blackwell, Kim T

    2017-04-01

    The striatum is a major site of learning and memory formation for sensorimotor and cognitive association. One of the mechanisms used by the brain for memory storage is synaptic plasticity - the long-lasting, activity-dependent change in synaptic strength. All forms of synaptic plasticity require an elevation in intracellular calcium, and a common hypothesis is that the amplitude and duration of calcium transients can determine the direction of synaptic plasticity. The utility of this hypothesis in the striatum is unclear in part because dopamine is required for striatal plasticity and in part because of the diversity in stimulation protocols. To test whether calcium can predict plasticity direction, we developed a calcium-based plasticity rule using a spiny projection neuron model with sophisticated calcium dynamics including calcium diffusion, buffering and pump extrusion. We utilized three spike timing-dependent plasticity (STDP) induction protocols, in which postsynaptic potentials are paired with precisely timed action potentials and the timing of such pairing determines whether potentiation or depression will occur. Results show that despite the variation in calcium dynamics, a single, calcium-based plasticity rule, which explicitly considers duration of calcium elevations, can explain the direction of synaptic weight change for all three STDP protocols. Additional simulations show that the plasticity rule correctly predicts the NMDA receptor dependence of long-term potentiation and the L-type channel dependence of long-term depression. By utilizing realistic calcium dynamics, the model reveals mechanisms controlling synaptic plasticity direction, and shows that the dynamics of calcium, not just calcium amplitude, are crucial for synaptic plasticity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Dysregulation of Elongation Factor 1A Expression is Correlated with Synaptic Plasticity Impairments in Alzheimer's Disease.

    PubMed

    Beckelman, Brenna C; Day, Stephen; Zhou, Xueyan; Donohue, Maggie; Gouras, Gunnar K; Klann, Eric; Keene, C Dirk; Ma, Tao

    2016-09-06

    Synaptic dysfunction may represent an early and crucial pathophysiology in Alzheimer's disease (AD). Recent studies implicate a connection between synaptic plasticity deficits and compromised capacity of de novo protein synthesis in AD. The mRNA translational factor eukaryotic elongation factor 1A (eEF1A) is critically involved in several forms of long-lasting synaptic plasticity. By examining postmortem human brain samples, a transgenic mouse model, and application of synthetic human Aβ42 on mouse hippocampal slices, we demonstrated that eEF1A protein levels were significantly decreased in AD, particularly in the hippocampus. In contrast, brain levels of eukaryotic elongation factor 2 were unaltered in AD. Further, upregulation of eEF1A expression by the adenylyl cyclase activator forskolin, which induces long-lasting synaptic plasticity, was blunted in hippocampal slices derived from Tg2576 AD model mice. Finally, Aβ-induced hippocampal long-term potentiation defects were alleviated by upregulation of eEF1A signaling via brain-specific knockdown of the gene encoding tuberous sclerosis 2. In summary, our findings suggest a strong correlation between the dysregulation of eEF1A synthesis and AD-associated synaptic failure. These findings provide insights into the understanding of molecular mechanisms underlying AD etiology and may aid in identification of novel biomarkers and therapeutic targets.

  1. Logarithmic distributions prove that intrinsic learning is Hebbian

    PubMed Central

    Scheler, Gabriele

    2017-01-01

    In this paper, we present data for the lognormal distributions of spike rates, synaptic weights and intrinsic excitability (gain) for neurons in various brain areas, such as auditory or visual cortex, hippocampus, cerebellum, striatum, midbrain nuclei. We find a remarkable consistency of heavy-tailed, specifically lognormal, distributions for rates, weights and gains in all brain areas examined. The difference between strongly recurrent and feed-forward connectivity (cortex vs. striatum and cerebellum), neurotransmitter (GABA (striatum) or glutamate (cortex)) or the level of activation (low in cortex, high in Purkinje cells and midbrain nuclei) turns out to be irrelevant for this feature. Logarithmic scale distribution of weights and gains appears to be a general, functional property in all cases analyzed. We then created a generic neural model to investigate adaptive learning rules that create and maintain lognormal distributions. We conclusively demonstrate that not only weights, but also intrinsic gains, need to have strong Hebbian learning in order to produce and maintain the experimentally attested distributions. This provides a solution to the long-standing question about the type of plasticity exhibited by intrinsic excitability. PMID:29071065

  2. Intrinsic DNA curvature in trypanosomes.

    PubMed

    Smircich, Pablo; El-Sayed, Najib M; Garat, Beatriz

    2017-11-09

    Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed. In order to study whether this feature is conserved in trypanosomatids, we undertook a genome wide search for intrinsic DNA curvature in T. cruzi and T. brucei. Using a region integrated intrinsic curvature (RIIC) scoring that we previously developed, a non-random distribution of sequence-dependent curvature was observed. High RIIC scores were found to be significantly correlated with transcription start sites in T. cruzi, which have been mapped in divergent switch regions, whereas in T. brucei, the high RIIC scores correlated with sites that have been involved not only in RNA polymerase II initiation but also in termination. In addition, we observed regions with high RIIC score presenting in-phase tracts of Adenines, in the subtelomeric regions of the T. brucei chromosomes that harbor the variable surface glycoproteins genes. In both T. cruzi and T. brucei genomes, a link between DNA conformational signals and gene expression was found. High sequence dependent curvature is associated with transcriptional regulation regions. High intrinsic curvature also occurs at the T. brucei chromosome subtelomeric regions where the recombination processes involved in the evasion of the immune host system take place. These findings underscore the relevance of indirect DNA readout in these ancient eukaryotes.

  3. The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins.

    PubMed

    Uversky, Vladimir N

    2013-01-01

    The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their "disorder promoting potencies," which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue.

  4. The alphabet of intrinsic disorder: I. Act like a Pro: On the abundance and roles of proline residues in intrinsically disordered proteins.

    PubMed

    Theillet, Francois-Xavier; Kalmar, Lajos; Tompa, Peter; Han, Kyou-Hoon; Selenko, Philipp; Dunker, A Keith; Daughdrill, Gary W; Uversky, Vladimir N

    2013-01-01

    A significant fraction of every proteome is occupied by biologically active proteins that do not form unique three-dimensional structures. These intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) have essential biological functions and are characterized by extensive structural plasticity. Such structural and functional behavior is encoded in the amino acid sequences of IDPs/IDPRs, which are enriched in disorder-promoting residues and depleted in order-promoting residues. In fact, amino acid residues can be arranged according to their disorder-promoting tendency to form an alphabet of intrinsic disorder that defines the structural complexity and diversity of IDPs/IDPRs. This review is the first in a series of publications dedicated to the roles that different amino acid residues play in defining the phenomenon of protein intrinsic disorder. We start with proline because data suggests that of the 20 common amino acid residues, this one is the most disorder-promoting.

  5. Our plastic age

    PubMed Central

    Thompson, Richard C.; Swan, Shanna H.; Moore, Charles J.; vom Saal, Frederick S.

    2009-01-01

    Within the last few decades, plastics have revolutionized our daily lives. Globally we use in excess of 260 million tonnes of plastic per annum, accounting for approximately 8 per cent of world oil production. In this Theme Issue of Philosophical Transactions of the Royal Society, we describe current and future trends in usage, together with the many benefits that plastics bring to society. At the same time, we examine the environmental consequences resulting from the accumulation of waste plastic, the effects of plastic debris on wildlife and concerns for human health that arise from the production, usage and disposal of plastics. Finally, we consider some possible solutions to these problems together with the research and policy priorities necessary for their implementation. PMID:19528049

  6. Our plastic age.

    PubMed

    Thompson, Richard C; Swan, Shanna H; Moore, Charles J; vom Saal, Frederick S

    2009-07-27

    Within the last few decades, plastics have revolutionized our daily lives. Globally we use in excess of 260 million tonnes of plastic per annum, accounting for approximately 8 per cent of world oil production. In this Theme Issue of Philosophical Transactions of the Royal Society, we describe current and future trends in usage, together with the many benefits that plastics bring to society. At the same time, we examine the environmental consequences resulting from the accumulation of waste plastic, the effects of plastic debris on wildlife and concerns for human health that arise from the production, usage and disposal of plastics. Finally, we consider some possible solutions to these problems together with the research and policy priorities necessary for their implementation.

  7. The plasticity of cyanobacterial carbon metabolism

    SciTech Connect

    Xiong, Wei; Cano, Melissa; Wang, Bo; Douchi, Damien; Yu, Jianping

    2017-09-29

    This opinion article aims to raise awareness of a fundamental issue which governs sustainable production of biofuels and bio-chemicals from photosynthetic cyanobacteria. Discussed is the plasticity of carbon metabolism, by which the cyanobacterial cells flexibly distribute intracellular carbon fluxes towards target products and adapt to environmental/genetic alterations. This intrinsic feature in cyanobacterial metabolism is being understood through recent identification of new biochemical reactions and engineering on low-throughput pathways. We focus our discussion on new insights into the nature of metabolic plasticity in cyanobacteria and its impact on hydrocarbons (e.g. ethylene and isoprene) production. Here, we discuss approaches that need to be developed to rationally rewire photosynthetic carbon fluxes throughout primary metabolism. We also outline open questions about the regulatory mechanisms of the metabolic network that remain to be answered, which might shed light on photosynthetic carbon metabolism and help optimize design principles in order to improve the production of fuels and chemicals in cyanobacteria.

  8. Receptor trafficking and the regulation of synaptic plasticity by SUMO.

    PubMed

    Luo, Jia; Ashikaga, Emi; Rubin, Philip P; Heimann, Michaela J; Hildick, Keri L; Bishop, Paul; Girach, Fatima; Josa-Prado, Fernando; Tang, Leo T H; Carmichael, Ruth E; Henley, Jeremy M; Wilkinson, Kevin A

    2013-12-01

    Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.

  9. Cocaine-induced plasticity in the cerebellum of sensitised mice.

    PubMed

    Vazquez-Sanroman, Dolores; Carbo-Gas, Maria; Leto, Ketty; Cerezo-Garcia, Miguel; Gil-Miravet, Isis; Sanchis-Segura, Carla; Carulli, Daniela; Rossi, Ferdinando; Miquel, Marta

    2015-12-01

    Prior research has accumulated a substantial amount of evidence on the ability of cocaine to produce short- and long-lasting molecular and structural plasticity in the corticostriatal-limbic circuitry. However, traditionally, the cerebellum has not been included in the addiction circuitry, even though growing evidence supports its involvement in the behavioural changes observed after repeated drug experiences. In the present study, we explored the ability of seven cocaine administrations to alter plasticity in the cerebellar vermis. After six cocaine injections, one injection every 48 h, mice remained undisturbed for 1 month in their home cages. Following this withdrawal period, they received a new cocaine injection of a lower dose. Locomotion, behavioural stereotypes and several molecular and structural cerebellar parameters were evaluated. Cerebellar proBDNF and mature BDNF levels were both enhanced by cocaine. The high BDNF expression was associated with dendritic sprouting and increased terminal size in Purkinje neurons. Additionally, we found a reduction in extracellular matrix components that might facilitate the subsequent remodelling of Purkinje-nuclear neuron synapses. Although speculative, it is possible that these cocaine-dependent cerebellar changes were incubated during withdrawal and manifested by the last drug injection. Importantly, the present findings indicate that cocaine is able to promote plasticity modifications in the cerebellum of sensitised animals similar to those in the basal ganglia.

  10. HDAC2 negatively regulates memory formation and synaptic plasticity

    PubMed Central

    Guan, Ji-Song; Haggarty, Stephen J.; Giacometti, Emanuela; Dannenberg, Jan-Hermen; Joseph, Nadine; Gao, Jun; Nieland, Thomas J.F.; Zhou, Ying; Wang, Xinyu; Mazitschek, Ralph; Bradner, James E.; DePinho, Ronald A.; Jaenisch, Rudolf; Tsai, Li-Huei

    2012-01-01

    Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wildtype mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACi requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not HDAC1, reduced dendritic spine density, synapse number, synaptic plasticity, and memory formation. Conversely, HDAC2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic HDACi treatment in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic HDACi treatment. Correspondingly, HDACi treatment failed to further facilitate memory formation in HDAC2-deficient mice. Furthermore, analysis of promoter occupancy revealed association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Together, our results suggest that HDAC2 plays a role in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment. PMID:19424149

  11. Plasticized phenolphthalein polycarbonate

    NASA Technical Reports Server (NTRS)

    Harrison, E. S.

    1976-01-01

    Phenolphthalein polycarbonate was successfully plasticized with polychlorinated biphenyls (e.g., Aroclor 1231) or tricresyl phosphate and cast from tetrahydrofuran to give clear films without loss of fire resistance. At loadings of 20 to 30 percent plasticizer the Tg was lowered to approximately 100 C which would render phenolphthalein polycarbonate easily moldable. Although these materials had some mechanical integrity as shown by their film forming ability, the room temperature toughness of the plasticized polymer was not significantly improved over unmodified polymer.

  12. What Is