Imaging and translational research: neuro degenerative diseases

International Nuclear Information System (INIS)

Hantraye, P.

2009-01-01

Advances in neuroimaging of neuro-degenerative diseases over the past two decades are the product of breakthroughs in imaging technology, more powerful computers, image-processing software, and expanding knowledge in basic and clinical neuro-science. In addition to the insights into normal brain structure and function that such methods provide, and the information that can be gained from disease-related changes in structure and function, functional imaging offers the promise of monitoring brain lesions and quantifying the therapeutic efficacy of innovative treatments for these largely incurable disorders. (author)

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

Directory of Open Access Journals (Sweden)

Vinet Jonathan

2012-01-01

Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

PET-based molecular nuclear neuro-imaging

International Nuclear Information System (INIS)

Kim, Jong Ho

2004-01-01

Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy

PET-based molecular nuclear neuro-imaging

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong Ho [Gil Medical Center, Gachon (Korea, Republic of)

2004-04-01

Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy.

BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB

Science.gov (United States)

Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)

2003-01-01

The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.

Is hair loss a reality in neuro-interventional radiology?

LENUS (Irish Health Repository)

Gavagan, L

2012-02-01

Reports in the literature of radiation-induced hair loss are becoming increasingly common. This work describes a retrospective dose study of patients (n = 958) undergoing diagnostic (primarily cerebral angiograms) and therapeutic (primarily cerebral embolisation) procedures in a neuro-interventional suite. A comparison of patient doses as dose area product (DAP) readings from a single-plane image intensifier system (mean DAP value of 8772 cGy cm(2)) were compared with patient doses from a flat panel biplane system (mean DAP value of 7855 cGy cm(2)). Over 80 % of patients requiring neuro-interventional procedures were found to undergo two procedures or more. An estimated 7 % of therapeutic procedures were found to reach the International Commission on Radiological Protection threshold for temporary epilation.

Development of PET tracers for neuro inflammation imaging in neuro degenerative diseases; Developpement de radiotraceurs de la neuroinflammation pour l'imagerie des pathologies neurodegeneratives

Energy Technology Data Exchange (ETDEWEB)

Chauveau, F

2007-10-15

Inflammatory processes such as micro-glial or endothelial activation are involved in many neuro-degenerative conditions. Neuro-inflammation imaging is considered an attractive tool for fundamental research, diagnosis and therapeutic evaluation in neuro-pathologies. First, an aptamer was selected against a recombinant fragment of the endothelial target VCAM-1, but proved unable to bind the target protein in native conformation, as expressed by a cell line. Second, five radioligands of the peripheral benzodiazepine receptor (PBR), a marker of micro-glial activation, were evaluated in vivo using PET (Positron Emission Tomography) imaging in a rat model of neuro-inflammation, and were compared to [11C]PK11195. Four radiotracers displayed a better contrast than [11C]PK11195. In a competitive field of research, this work demonstrates the efficiency of in vivo screening of radiotracers for fast selection of clinically relevant molecules. (author)

Novel application of stem cell-derived neurons to evaluate the time- and dose-dependent progression of excitotoxic injury.

Directory of Open Access Journals (Sweden)

Ian M Gut

Full Text Available Glutamate receptor (GluR-mediated neurotoxicity is implicated in a variety of disorders ranging from ischemia to neural degeneration. Under conditions of elevated glutamate, the excessive activation of GluRs causes internalization of pathologic levels of Ca(2+, culminating in bioenergetic failure, organelle degradation, and cell death. Efforts to characterize cellular and molecular aspects of excitotoxicity and conduct therapeutic screening for pharmacologic inhibitors of excitogenic progression have been hindered by limitations associated with primary neuron culture. To address this, we evaluated glutamate-induced neurotoxicity in highly enriched glutamatergic neurons (ESNs derived from murine embryonic stem cells. As of 18 days in vitro (DIV 18, ESNs were synaptically coupled, exhibited spontaneous network activity with neurotypic mEPSCs and expressed NMDARs and AMPARs with physiological current:voltage behaviors. Addition of 0.78-200 μM glutamate evoked reproducible time- and dose-dependent metabolic failure in 6 h, with a calculated EC50 value of 0.44 μM at 24 h. Using a combination of cell viability assays and electrophysiology, we determined that glutamate-induced toxicity was specifically mediated by NMDARs and could be inhibited by addition of NMDAR antagonists, increased extracellular Mg(2+ or substitution of Ba(2+ for Ca(2+. Glutamate treatment evoked neurite fragmentation and focal swelling by both immunocytochemistry and scanning electron microscopy. Presentation of morphological markers of cell death was dose-dependent, with 0.78-200 μM glutamate resulting in apoptosis and 3000 μM glutamate generating a mixture of necrosis and apoptosis. Addition of neuroprotective small molecules reduced glutamate-induced neurotoxicity in a dose-dependent fashion. These data indicate that ESNs replicate many of the excitogenic mechanisms observed in primary neuron culture, offering a moderate-throughput model of excitotoxicity that combines the

The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential

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Johannes Burtscher

2017-08-01

Full Text Available Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients often develop cognitive deficits and emotional blunting along the progression of the disease. The high incidence of resistance to antiepileptic drugs and a frequent lack of admissibility to surgery poses an unmet medical challenge. In the urgent quest of novel treatment strategies, neuropeptides are interesting candidates, however, their therapeutic potential has not yet been exploited. This review focuses on the functional role of the endogenous opioid system with respect to temporal lobe epilepsy, specifically in the hippocampus. The role of dynorphins and kappa opioid receptors (KOPr as modulators of neuronal excitability is well understood: both the reduced release of glutamate as well of postsynaptic hyperpolarization were shown in glutamatergic neurons. In line with this, low levels of dynorphin in humans and mice increase the risk of epilepsy development. The role of enkephalins is not understood so well. On one hand, some agonists of the delta opioid receptors (DOPr display pro-convulsant properties probably through inhibition of GABAergic interneurons. On the other hand, enkephalins play a neuro-protective role under hypoxic or anoxic conditions, most probably through positive effects on mitochondrial function. Despite the supposed absence of endorphins in the hippocampus, exogenous activation of the mu opioid receptors (MOPr induces pro-convulsant effects. Recently-expanded knowledge of the complex ways opioid receptors ligands elicit their effects (including biased agonism, mixed binding, and opioid receptor heteromers, opens up exciting new therapeutic potentials with regards to seizures and epilepsy. Potential adverse side effects of KOPr agonists may be minimized through functional selectivity. Preclinical data suggest a high potential of such compounds to control seizures, with a strong predictive validity toward human

Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

DEFF Research Database (Denmark)

Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R

1993-01-01

In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

Development of PET tracers for neuro inflammation imaging in neuro degenerative diseases; Developpement de radiotraceurs de la neuroinflammation pour l'imagerie des pathologies neurodegeneratives

Energy Technology Data Exchange (ETDEWEB)

Chauveau, F

2007-10-15

Inflammatory processes such as micro-glial or endothelial activation are involved in many neuro-degenerative conditions. Neuro-inflammation imaging is considered an attractive tool for fundamental research, diagnosis and therapeutic evaluation in neuro-pathologies. First, an aptamer was selected against a recombinant fragment of the endothelial target VCAM-1, but proved unable to bind the target protein in native conformation, as expressed by a cell line. Second, five radioligands of the peripheral benzodiazepine receptor (PBR), a marker of micro-glial activation, were evaluated in vivo using PET (Positron Emission Tomography) imaging in a rat model of neuro-inflammation, and were compared to [11C]PK11195. Four radiotracers displayed a better contrast than [11C]PK11195. In a competitive field of research, this work demonstrates the efficiency of in vivo screening of radiotracers for fast selection of clinically relevant molecules. (author)

Neuro-ophthalmology update.

Science.gov (United States)

Weber, Konrad P; Straumann, Dominik

2014-07-01

This review summarizes the most relevant articles from the field of neuro-ophthalmology published in the Journal of Neurology from January 2012 to July 2013. With the advent of video-oculography, several articles describe new applications for eye movement recordings as a diagnostic tool for a wide range of disorders. In myasthenia gravis, anti-Kv1.4 and anti-Lrp4 have been characterized as promising novel autoantibodies for the diagnosis of hitherto 'seronegative' myasthenia gravis. Several articles address new diagnostic and therapeutic approaches to neuromyelitis optica, which further sharpen its profile as a distinct entity. Additionally, 4-aminopyridine has become a standard therapeutic for patients with cerebellar downbeat nystagmus. Finally, revised diagnostic criteria have been proposed for chronic relapsing inflammatory optic neuropathy based on a careful literature review over the last decade.

Excitotoxicity and neuronal death in epilepsy

OpenAIRE

Lorigados, Lourdes; Orozco, Sandra; Morales, Lilia; Estupiñán, Bárbara; García, Iván; Rocha, Luisa

2013-01-01

Epilepsy is a recurrent, often progressive neurological disorder with a chronic evolution, affecting 1 to 2 % of the world population. Research with experimental models and imaging analysis of diseased patients have been used to show that recurrent episodes produce oxidative stress, most of which is related to neuronal excitability phenomena. It is known that the excessive stimulation of glutamate receptors results in neurotoxicity; a process that, under the denomination of excitotoxicity, is...

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease

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Despina Kokona

2016-01-01

Full Text Available The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP. This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease.

An evaluation of Neuro-Physiological Psychotherapy: An integrative therapeutic approach to working with adopted children who have experienced early life trauma.

Science.gov (United States)

McCullough, Elaine; Gordon-Jones, Susi; Last, Anna; Vaughan, Jay; Burnell, Alan

2016-10-01

Research into the effectiveness of therapeutic interventions for older children who have experienced multiple forms of trauma within the context of their early development is scant. This article explores the effectiveness of Neuro-Physiological Psychotherapy (NPP): a wrap-around multi-disciplinary, neuro-sequential, attachment-focussed intervention for children and families who present with multiple, clinically significant, emotional and behavioural difficulties. In total, 31 young people and their adoptive parents took part in the study. Baseline measures were repeated and parents and children interviewed. An assessment of the parent/child relationship and child attachment was undertaken but not analysed for this article. Analysis of the repeated measures received statistically significant changes in behavioural regulation, metacognitive executive functioning and externalising and internalising difficulties, alongside an improvement in thought and social problems. An analysis of the parent interviews provided positive results in terms of the children's engagement in education, an absence of further mental health diagnosis or involvement in the criminal justice system. Further hypotheses are posited regarding the impact of the treatment and further research into the effectiveness of the model outlined. © The Author(s) 2016.

Single-cell imaging of bioenergetic responses to neuronal excitotoxicity and oxygen and glucose deprivation.

Science.gov (United States)

Connolly, Niamh M C; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen H M

2014-07-30

Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca(2+)/Na(+) influx into neurons, energetic stress, and subsequent neuronal injury. We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contribution of effects of non-neuronal cells. Hence, we here characterized bioenergetics during transient excitotoxicity in rat and mouse primary neurons at the single-cell level using fluorescent sensors for intracellular glucose, ATP, and activation of the energy sensor AMP-activated protein kinase (AMPK). We identified ATP depletion and recovery to energetic homeostasis, along with AMPK activation, as surprisingly rapid and plastic responses in two excitotoxic injury paradigms. We observed rapid recovery of neuronal ATP levels also in the absence of extracellular glucose, or when glycolytic ATP production was inhibited, but found mitochondria to be critical for fast and complete energetic recovery. Using an injury model of oxygen and glucose deprivation, we identified a similarly rapid bioenergetics response, yet with incomplete ATP recovery and decreased AMPK activity. Interestingly, excitotoxicity also induced an accumulation of intracellular glucose, providing an additional source of energy during and after excitotoxicity-induced energy depletion. We identified this to originate from extracellular, AMPK-dependent glucose uptake and from intracellular glucose mobilization. Surprisingly, cells recovering their elevated glucose levels faster to baseline survived longer, indicating that the plasticity of neurons to adapt to bioenergetic challenges is a key indicator of neuronal viability. Copyright © 2014 the authors 0270-6474/14/3410192-14$15.00/0.

MRI in neuro-Behcet's disease

International Nuclear Information System (INIS)

Tali, E.T.; Atilla, S.; Keskin, T.; Simonson, T.; Isik, S.; Yuh, W.T.C.

1997-01-01

Our purpose was to characterise specific MRI findings and to determine their value in neuro-Behcet's disease. We examined 17 patients (14 men, 3 women) with neuro-Behcet's disease using T1- and T2-weighted spin-echo images and contrast-enhanced images at 0.5 T. There were 13 patients (76.5 %) who had single or multiple lesions. Most of these were in the basal ganglia, brain stem or deep white matter region, giving high signal on T2-weighted images and isointense or low signal on T1-weighted images. In 3 cases (17.6 %) there was linear high signal along the posterior limb of the internal capsule on T2-weighted images. This was considered as a potential differentiating feature of neuro-Behcet's disease. Contrast-enhancement was seen in 17 lesions in 7 patients. (orig.). With 5 figs., 2 tabs

GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

DEFF Research Database (Denmark)

Bonde, C; Kristensen, B W; Blaabjerg, M

2000-01-01

-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN......The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN...

Parent perceptions of the quality of life of pet dogs living with neuro-typically developing and neuro-atypically developing children: An exploratory study.

Science.gov (United States)

Hall, Sophie S; Wright, Hannah F; Mills, Daniel S

2017-01-01

There is growing scientific and societal recognition of the role that pet dogs can play in healthy development of children; both those who are neuro-typically developing and those who live with a neuro-developmental disorder, such as autism or attention deficit hyperactivity disorder. However, little attention has been paid to how living with children positively and negatively affects quality of life of a pet dog. In this exploratory study we conducted semi-structured interviews with parents of neuro-typically developing children (n = 18) and those with a neuro-developmental disorder (n = 18) who owned a pet dog, until no new factors were identified. Living with children brought potentially positive benefits to the dog's life including: imposition of a routine, participation in recreational activities and the development of a strong bond between the child and the dog. The importance of maintaining a routine was particularly prevalent in families with children with neuro-developmental disorders. Potential negative factors included having to cope with child meltdowns and tantrums, over stimulation from child visitors, harsh contact and rough and tumble play with the child. The regularity and intensity of meltdowns and tantrums was particularly evident in responses from parents with children with a neuro-developmental disorder. However, child visitors and rough play and contact were mentioned similarly across the groups. Protective factors included having a safe haven for the dog to escape to, parent's awareness of stress signs and child education in dog-interaction. Parents were also asked to complete a stress response scale to provide an initial quantitative comparison of stress responses between dogs living with the two family-types. Parents with neuro-typically developing children more frequently observed their dog rapidly running away from a situation and less frequently observed their dog widening their eyes, than parents with children with a neuro

Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats

DEFF Research Database (Denmark)

Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá

2017-01-01

Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also...... assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects...... be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were...

Delayed Administration of VEGF Rescues Spinal Motor Neurons from Death with a Short Effective Time Frame in Excitotoxic Experimental Models in Vivo

Directory of Open Access Journals (Sweden)

Luis B Tovar-y-Romo

2012-02-01

Full Text Available VEGF (vascular endothelial growth factor prevents neuronal death in different models of ALS (amyotrophic lateral sclerosis, but few studies have addressed the efficacy of VEGF to protect motor neurons after the onset of symptoms, a critical point when considering VEGF as a potential therapeutic target for ALS. We studied the capability of VEGF to protect motor neurons after an excitotoxic challenge in two models of spinal neurodegeneration in rats induced by AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid administered either chronically with osmotic minipumps or acutely by microdialysis. VEGF was administered through osmotic minipumps in the chronic model or injected intracerebroventricularly in the acute model, and its effects were assessed by immunohistochemical and histological analyses and motor performance tests. In the chronic model, VEGF stopped the progression of the paralysis and protected motor neurons when administered after AMPA before the onset of the motor symptoms, whereas no protection was observed when administered after the onset. VEGF was also protective in the acute model, but with a short time window, since the protection was effective when administered 1 h but not 2 h after AMPA. Our results indicate that while VEGF has an indubitable neuroprotective effect, its therapeutic potential for halting or delaying the progression of motor neuron loss in ALS would likely have a short effective time frame.

Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

DEFF Research Database (Denmark)

Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.

2002-01-01

-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest...... receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA...... a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo....

Red Ginseng Extract Attenuates Kainate-Induced Excitotoxicity by Antioxidative Effects

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Jin-Yi Han

2012-01-01

Full Text Available This study investigated the neuroprotective activity of red ginseng extract (RGE, Panax ginseng, C. A. Meyer against kainic acid- (KA- induced excitotoxicity in vitro and in vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the MTT assay. To study the possible mechanisms of the RGE-mediated neuroprotective effect against KA-induced cytotoxicity, we examined the levels of intracellular reactive oxygen species (ROS and [Ca2+]i in cultured hippocampal neurons and found that RGE treatment dose-dependently inhibited intracellular ROS and [Ca2+]i elevation. Oral administration of RGE (30 and 200 mg/kg in mice decreased the malondialdehyde (MDA level induced by KA injection (30 mg/kg, i.p.. In addition, similar results were obtained after pretreatment with the radical scavengers Trolox and N, N′-dimethylthiourea (DMTU. Finally, after confirming the protective effect of RGE on hippocampal brain-derived neurotropic factor (BDNF protein levels, we found that RGE is active compounds mixture in KA-induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals, and the IC50 was approximately 10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl radical (•OH, was similar to trolox. The second-order rate constant of RGE for •OH was 3.5–4.5×109 M−1·S−1. Therefore, these results indicate that RGE possesses radical reduction activity and alleviates KA-induced excitotoxicity by quenching ROS in hippocampal neurons.

Parent perceptions of the quality of life of pet dogs living with neuro-typically developing and neuro-atypically developing children: An exploratory study.

Directory of Open Access Journals (Sweden)

Sophie S Hall

Full Text Available There is growing scientific and societal recognition of the role that pet dogs can play in healthy development of children; both those who are neuro-typically developing and those who live with a neuro-developmental disorder, such as autism or attention deficit hyperactivity disorder. However, little attention has been paid to how living with children positively and negatively affects quality of life of a pet dog. In this exploratory study we conducted semi-structured interviews with parents of neuro-typically developing children (n = 18 and those with a neuro-developmental disorder (n = 18 who owned a pet dog, until no new factors were identified. Living with children brought potentially positive benefits to the dog's life including: imposition of a routine, participation in recreational activities and the development of a strong bond between the child and the dog. The importance of maintaining a routine was particularly prevalent in families with children with neuro-developmental disorders. Potential negative factors included having to cope with child meltdowns and tantrums, over stimulation from child visitors, harsh contact and rough and tumble play with the child. The regularity and intensity of meltdowns and tantrums was particularly evident in responses from parents with children with a neuro-developmental disorder. However, child visitors and rough play and contact were mentioned similarly across the groups. Protective factors included having a safe haven for the dog to escape to, parent's awareness of stress signs and child education in dog-interaction. Parents were also asked to complete a stress response scale to provide an initial quantitative comparison of stress responses between dogs living with the two family-types. Parents with neuro-typically developing children more frequently observed their dog rapidly running away from a situation and less frequently observed their dog widening their eyes, than parents with children with a

Neuro-ophthalmology as a career.

Science.gov (United States)

Spitze, Arielle; Al-Zubidi, Nagham; Lam, Peter; Yalamanchili, Sushma; Lee, Andrew G

2014-10-01

This essay was written to discuss the reasoning behind the personal decisions made by 2 current neuro-ophthalmology fellows to pursue neuro-ophthalmology as a career. It is meant to enlighten the reader about what role neuro-ophthalmologists play in clinical practice, what makes neuro-ophthalmology unique to all other sub-specialties, and how this contributes to making neuro-ophthalmology not only one of the most medically interesting, yet rewarding sub-specialties in ophthalmology.

A new infectious encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX).

Science.gov (United States)

Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Yasukawa, Kumi; Takanashi, Jun-Ichi

2017-09-15

Acute infectious encephalopathy is often observed in children in East Asia including Japan. More than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanisms in those with unclassified encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among seven patients with acute encephalopathy admitted to our hospital from June 2016 to May 2017, three were classified into acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). The other four showed consciousness disturbance lasting more than three days with no parenchymal lesion visible on MRI, which led to a diagnosis of unclassified encephalopathy. MR spectroscopy in these four patients, however, revealed an increase of glutamine with a normal N-acetyl aspartate level on days 5 to 8, which had normalized by follow-up studies on days 11 to 16. The four patients clinically recovered completely. Among 27 patients with encephalopathy, including the present seven patients, admitted to our hospital from January 2015 to March 2017, seven (26%) were classified into this type, which we propose is a new encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX). MEEX is the second most common subtype, following AESD (30%). This study suggests that excitotoxicity may be a common underlying pathomechanism of acute infectious encephalopathy, and prompt astrocytic neuroprotection from excitotoxicity may prevent progression of MEEX into AESD. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential therapeutic applications of biosurfactants.

Science.gov (United States)

Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

2013-12-01

Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS.

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Vidya Sagar

Full Text Available The neurological complications of AIDS (neuroAIDS during the infection of human immunodeficiency virus (HIV are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome. These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying-and so far unknown-genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.

Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

DEFF Research Database (Denmark)

Kristensen, B W; Noraberg, J; Jakobsen, B

1999-01-01

of the cytosolic enzyme lactate dehydrogenase (LDH) into the culture medium and loss of glutamic acid decarboxylase (GAD) activity in the tissue. Histological sections were also stained by the fluorescent dye Fluoro-Jade (FJ), for degenerating neurons and by immunocytochemical staining for gamma-aminobutyric acid...... density of Fluoro-Jade staining, (3) loss of GAD-activity in tissue homogenates, and (4) loss of GABA-immunostained neurons. We conclude that both differences between compounds (AMPA vs. KA) and brain areas (striatum vs. cortex) can be demonstrated in corticostriatal slice cultures, which in conjunction...... in corticostriatal slice cultures. The purpose was to examine the feasibility of these cultures for excitotoxic studies, and to demonstrate possible differential excitotoxic effects of KA and AMPA on striatal and cortical neurons. Slices of dorsolateral striatum with overlying neocortex were obtained from neonatal...

Clinical point of view, imaging and neuro physiology of the case with diagnosis of neuro fibrosarcomas sacrococcigeo

International Nuclear Information System (INIS)

Hernandez Hernandez, Barbara Aymee; Brown Martinez, Marta

2004-01-01

It was considered a case with diagnosis of neuro fibrosarcomas sacrococcigeo, which was very well studied from the clinical point of view, imaging and neuro physiology; with the objective of showing the correlation degree among these studies. He/she was carried out study of nervous conduction of nerve later, reflective tibial H, electromiografia of dependent muscles of the plexo lumbosacro, potentials evoked somatosensoriales and wave F of nerve later tibial. With this the existence of a functional dysfunction was demonstrated in the medullary segments from L4-S2 with prevalence motor. He/she was also carried out mielografia and nuclear magnetic resonance that it evidenced the existence from an expansible process to the level sacrococcigeo. The utility of the neuro physiological studies was demonstrated in the diagnosis of affections tumorales, cocktails with the imagenological studies that define the anatomical alterations and the diagnosis morfofuncional of these pathologies is completed

The insulin/IGF signaling regulators cytohesin/GRP-1 and PIP5K/PPK-1 modulate susceptibility to excitotoxicity in C. elegans.

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Nazila Tehrani

Full Text Available During ischemic stroke, malfunction of excitatory amino acid transporters and reduced synaptic clearance causes accumulation of Glutamate (Glu and excessive stimulation of postsynaptic neurons, which can lead to their degeneration by excitotoxicity. The balance between cell death-promoting (neurotoxic and survival-promoting (neuroprotective signaling cascades determines the fate of neurons exposed to the excitotoxic insult. The evolutionary conserved Insulin/IGF Signaling (IIS cascade can participate in this balance, as it controls cell stress resistance in nematodes and mammals. Blocking the IIS cascade allows the transcription factor FoxO3/DAF-16 to accumulate in the nucleus and activate a transcriptional program that protects cells from a range of insults. We study the effect of IIS cascade on neurodegeneration in a C. elegans model of excitotoxicity, where a mutation in a central Glu transporter (glt-3 in a sensitizing background causes Glu-Receptor -dependent neuronal necrosis. We expand our studies on the role of the IIS cascade in determining susceptibility to excitotoxic necrosis by either blocking IIS at the level of PI3K/AGE-1 or stimulating it by removing the inhibitory effect of ZFP-1 on the expression of PDK-1. We further show that the components of the Cytohesin/GRP-1, Arf, and PIP5K/PPK-1 complex, known to regulate PIP2 production and the IIS cascade, modulate nematode excitotoxicity: mutations that are expected to reduce the complex's ability to produce PIP2 and inhibit the IIS cascade protect from excitotoxicity, while overstimulation of PIP2 production enhances neurodegeneration. Our observations therefore affirm the importance of the IIS cascade in determining the susceptibility to necrotic neurodegeneration in nematode excitotoxicity, and demonstrate the ability of Cytohesin/GRP-1, Arf, and PIP5K/PPK-1 complex to modulate neuroprotection.

Neuro-Oncology Branch

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... BTTC are experts in their respective fields. Neuro-Oncology Clinical Fellowship This is a joint program with ... can increase survival rates. Learn more... The Neuro-Oncology Branch welcomes Dr. Mark Gilbert as new Branch ...

Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding

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Svetlana A. Ivanova

2016-01-01

Full Text Available A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington’s disease. Huntington’s disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs: postsynaptic density- (PSD- 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson’s disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.

Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit: an in silico study elucidating a novel mechanism of action of the drug.

Science.gov (United States)

Mazumder, Muhammed Khairujjaman; Borah, Anupom

2014-12-01

Hyperactivation of GluN2B subunit containing N-methyl-d-aspartate receptors (NMDARs) significantly contributes to the development of several neurodegenerative diseases through a process called excitotoxicity. NMDARs are voltage-gated Ca2+ channels which when activated lead to excessive influx of Ca2+ into neurons thereby exacerbating several calcium-dependent pathways that cause oxidative stress and apoptosis. Several drugs are presently in use to counter the NMDAR-mediated excitotoxic events among which Ifenprodil and its derivatives are GluN2B selective allosteric antagonists. Certain non-steroidal anti-inflammatory drugs (NSAIDs) have also been reported to inhibit NMDARs and the resultant pathologies. Meanwhile, Piroxicam, which is a NSAID, has been reported to be protective in cerebral ischemia-induced neurodegeneration through various pathways. Since Piroxicam has more number of interacting groups as compared to other NSAIDs and also has structural similarities with Ifenprodil, we thought it prudent that Piroxicam may inhibit NMDARs similar to Ifenprodil. By using molecular docking as a tool, we validated the hypothesis and hereby report for the first time that Piroxicam can inhibit GluN2B containing NMDARs through allosteric mode similar to the well known selective antagonist--Ifenprodil; and thus can be a therapeutic drug for the prevention of excitotoxic neurodegeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pilocarpine-induced status epilepticus in rats involves ischemic and excitotoxic mechanisms.

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Paolo Francesco Fabene

Full Text Available The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE. Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology.

Neuro-otological and peripheral nerve involvement in Fabry disease

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Sergio Carmona

2017-07-01

Full Text Available Fabry disease (FD is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain, vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%, vertigo (27.8% or both (25%. An involvement of either cochlear or vestibular function was identified in most patients (75%. In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neurootological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

ASIC channel inhibition enhances excitotoxic neuronal death in an in vitro model of spinal cord injury.

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Mazzone, Graciela L; Veeraraghavan, Priyadharishini; Gonzalez-Inchauspe, Carlota; Nistri, Andrea; Uchitel, Osvaldo D

2017-02-20

In the spinal cord high extracellular glutamate evokes excitotoxic damage with neuronal loss and severe locomotor impairment. During the cell dysfunction process, extracellular pH becomes acid and may activate acid-sensing ion channels (ASICs) which could be important contributors to neurodegenerative pathologies. Our previous studies have shown that transient application of the glutamate analog kainate (KA) evokes delayed excitotoxic death of spinal neurons, while white matter is mainly spared. The present goal was to enquire if ASIC channels modulated KA damage in relation to locomotor network function and cell death. Mouse spinal cord slices were treated with KA (0.01 or 0.1mM) for 1h, and then washed out for 24h prior to analysis. RT-PCR results showed that KA (at 0.01mM concentration that is near-threshold for damage) increased mRNA expression of ASIC1a, ASIC1b, ASIC2 and ASIC3, an effect reversed by the ASIC inhibitor 4',6-diamidino-2-phenylindole (DAPI). A KA neurotoxic dose (0.1mM) reduced ASIC1a and ASIC2 expression. Cell viability assays demonstrated KA-induced large damage in spinal slices from mice with ASIC1a gene ablation. Likewise, immunohistochemistry indicated significant neuronal loss when KA was followed by the ASIC inhibitors DAPI or amiloride. Electrophysiological recording from ventral roots of isolated spinal cords showed that alternating oscillatory cycles were slowed down by 0.01mMKA, and intensely inhibited by subsequently applied DAPI or amiloride. Our data suggest that early rise in ASIC expression and function counteracted deleterious effects on spinal networks by raising the excitotoxicity threshold, a result with potential implications for improving neuroprotection. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Clinical Nihilism in Neuro-Emergencies

Science.gov (United States)

Hemphill, J. Claude; White, Douglas B.

2009-01-01

Mortality and morbidity remain high from neurological emergencies such as acute stroke, traumatic brain injury, and hypoxic-ischemic encephalopathy after cardiac arrest. Decisions regarding initial aggressiveness of care must be made at the time of presentation and perceived prognosis is often used as part of this decision-making process. However, these decisions are predicated on the accuracy of early outcome prediction. Decisions to limit treatment early after neuro-emergencies must be balanced with avoidance of self-fulfilling prophecies of poor outcome due to clinical nihilism. This article examines the role of prognostication early after neuro-emergencies, the potential impact of early treatment limitations, and how these may relate to communication with patients and surrogate decision makers in the context of these acute neurological events. PMID:19218017

Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury

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Bryan Leaw

2017-07-01

Full Text Available Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI, there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.

Force spectroscopy measurements show that cortical neurons exposed to excitotoxic agonists stiffen before showing evidence of bleb damage.

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Shan Zou

Full Text Available In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D-aspartic acid, NMDA and sodium (Nav channels trigger excitotoxic neuron death. Na(+, Ca(++ and H2O influx into affected neurons elicits swelling (increased cell volume and pathological blebbing (disassociation of the plasma membrane's bilayer from its spectrin-actomyosin matrix. Though usually conflated in injured tissue, cell swelling and blebbing are distinct processes. Around an injury core, salvageable neurons could be mildly swollen without yet having suffered the bleb-type membrane damage that, by rendering channels leaky and pumps dysfunctional, exacerbates the excitotoxic positive feedback spiral. Recognizing when neuronal inflation signifies non-lethal osmotic swelling versus blebbing should further efforts to salvage injury-penumbra neurons. To assess whether the mechanical properties of osmotically-swollen versus excitotoxically-blebbing neurons might be cytomechanically distinguishable, we measured cortical neuron elasticity (gauged via atomic force microscopy (AFM-based force spectroscopy upon brief exposure to hypotonicity or to excitotoxic agonists (glutamate and Nav channel activators, NMDA and veratridine. Though unperturbed by solution exchange per se, elasticity increased abruptly with hypotonicity, with NMDA and with veratridine. Neurons then invariably softened towards or below the pre-treatment level, sometimes starting before the washout. The initial channel-mediated stiffening bespeaks an abrupt elevation of hydrostatic pressure linked to NMDA or Nav channel-mediated ion/H2O fluxes, together with increased [Ca(++]int-mediated submembrane actomyosin contractility. The subsequent softening to below-control levels is consistent with the onset of a lethal level of bleb damage. These findings indicate that dissection/identification of molecular events during the excitotoxic transition from stiff/swollen to soft/blebbing is warranted and should be

Neuro-Music Therapy for Recent-Onset Tinnitus

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Miriam Grapp

2013-05-01

Full Text Available The aim of this pilot study was the evaluation of the neuro-music therapy approach as a new treatment option for patients with recent-onset tinnitus whose tinnitus symptoms were enduring after initial pharmacological treatment. In all, 15 patients with recent-onset tinnitus took part in our manualized short-term music-therapeutic treatment. Tinnitus severity and individual tinnitus distress were assessed by the German version of the tinnitus questionnaire (TQ and the Attention and Performance Self-Assessment Scale (APSA at three different measurement times: baseline (T0, start of treatment (T1, and end of treatment (T2. Score changes in TQ and APSA from start to end of treatment indicated significant improvements in tinnitus-related distress. According to the Jacobson and Truax reliable change index (RC, 73.3% of the patients showed a reliable reduction in individual TQ-score. The neuro-music therapy for recent-onset tinnitus according to the “Heidelberg Model” introduced in this pilot study seems to provide an effective treatment option for patients with recent-onset tinnitus.

Green Tea Polyphenols Attenuated Glutamate Excitotoxicity via Antioxidative and Antiapoptotic Pathway in the Primary Cultured Cortical Neurons

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Lin Cong

2016-01-01

Full Text Available Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury

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Chiu Li Shan

2017-11-01

Full Text Available Cationic arginine-rich and poly-arginine peptides (referred to as CARPs have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model, R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.

Intracranial Aneurysms of Neuro-Ophthalmologic Relevance.

Science.gov (United States)

Micieli, Jonathan A; Newman, Nancy J; Barrow, Daniel L; Biousse, Valérie

2017-12-01

Intracranial saccular aneurysms are acquired lesions that often present with neuro-ophthalmologic symptoms and signs. Recent advances in neurosurgical techniques, endovascular treatments, and neurocritical care have improved the optimal management of symptomatic unruptured aneurysms, but whether the chosen treatment has an impact on neuro-ophthalmologic outcomes remains debated. A review of the literature focused on neuro-ophthalmic manifestations and treatment of intracranial aneurysms with specific relevance to neuro-ophthalmologic outcomes was conducted using Ovid MEDLINE and EMBASE databases. Cavernous sinus aneurysms were not included in this review. Surgical clipping vs endovascular coiling for aneurysms causing third nerve palsies was compared in 13 retrospective studies representing 447 patients. Complete recovery was achieved in 78% of surgical patients compared with 44% of patients treated with endovascular coiling. However, the complication rate, hospital costs, and days spent in intensive care were reported as higher in surgically treated patients. Retrospective reviews of surgical clipping and endovascular coiling for all ocular motor nerve palsies (third, fourth, or sixth cranial nerves) revealed similar results of complete resolution in 76% and 49%, respectively. Improvement in visual deficits related to aneurysmal compression of the anterior visual pathways was also better among patients treated with clipping than with coiling. The time to treatment from onset of visual symptoms was a predictive factor of visual recovery in several studies. Few reports have specifically assessed the improvement of visual deficits after treatment with flow diverters. Decisions regarding the choice of therapy for intracranial aneurysms causing neuro-ophthalmologic signs ideally should be made at high-volume centers with access to both surgical and endovascular treatments. The status of the patient, location of the aneurysm, and experience of the treating physicians

SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons

International Nuclear Information System (INIS)

Jia, Ning; Sun, Qinru; Su, Qian; Chen, Guomin

2016-01-01

It is widely accepted that accumulation of extracellular glutamate mediates neuronal injuries in a number of neurological disorders via binding glutamate receptors. However, usage of the glutamate receptor antagonists aimed to prevent glutamate excitotoxicity is still controversial. As a polyphenol natural product, curcumin, has been implied multiple bioactivities. In this study, we explored whether the silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-coactivator 1α (PGC1α) pathway participated in the protection of curcumin against glutamate excitotoxicity. The cultured primary cortical neurons were treated with glutamate to set up a neuronal excitotoxicity model. The MTT and TUNEL methods were employed to measure cell viability and apoptosis, respectively. The mitochondrial function, the expression levels of SIRT1, PGC1α and acetylated PGC1α (ac-PGC1α) were measured to explore the mechanism of curcumin against glutamate excitotoxicity. The results showed that glutamate significantly induced cell death and apoptosis, which was blocked by pretreatment with curcumin. Meanwhile, curcumin preserved mitochondrial function, increased the expression level of SIRT1 and reduced the level of ac-PGC1α in the presence of glutamate. These results suggest that SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin against glutamate excitotoxicity. - Highlights: • Curcumin attenuates glutamate induced cell death and apoptosis in cultured neurons. • Curcumin preserves mitochondrial function in the presence of glutamate. • Curcumin enhanced the expression of SIRT1 in the glutamate rich environment. • SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin.

Urgences en neuro-ophtalmologie

DEFF Research Database (Denmark)

Caignard, A.; Leruez, S.; Milea, D.

2017-01-01

Neuro-ophthalmic emergencies can cause life-threatening or sight-threatening complications. Various conditions may have acute neuro-ophthalmic manifestations, including inflammatory or ischemic processes, as well as tumoral, aneurysmal compression or metabolic and systemic diseases. Diplopia...

Therapeutic potential of curcumin in gastrointestinal diseases

OpenAIRE

Rajasekaran, Sigrid A

2011-01-01

Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more system...

Neuro-ophthalmology and neuro-otology update.

Science.gov (United States)

Gold, Daniel R; Zee, David S

2015-12-01

This review summarizes topical papers from the fields of neuro-ophthalmology and neuro-otology published from August 2013 to February 2015. The main findings are: (1) diagnostic criteria for pseudotumor cerebri have been updated, and the Idiopathic Intracranial Hypertension Treatment Trial evaluated the efficacy of acetazolamide in patients with mild vision loss, (2) categorization of vestibular disorders through history and ocular motor examination is particularly important in the acute vestibular syndrome, where timely distinction between a central or peripheral localization is essential, (3) the newly described "sagging eye syndrome" provides a mechanical explanation for an isolated esodeviation that increases at distance in the aging population and (4) eye movement recordings better define how cerebellar dysfunction and/or sixth nerve palsy may play a role in other patients with esodeviations that increase at distance.

IGF-1-Involved Negative Feedback of NR2B NMDA Subunits Protects Cultured Hippocampal Neurons Against NMDA-Induced Excitotoxicity.

Science.gov (United States)

Li, Yun; Sun, Wei; Han, Song; Li, Jianing; Ding, Shu; Wang, Wei; Yin, Yanling

2017-01-01

Insulin-like growth factor 1 (IGF-1) is a multifunctional protein involved in neuronal polarity and axonal guidance. In our previous study, it was discovered that IGF-1 alleviated 50-μM NMDA-induced excitotoxicity against neuronal autophagy via depression of NR2B p-Ser1303 activation. However, it was found that NMDA at a higher dose did not cause neuronal autophagy. And, the performance of IGF-1 under severe excitotoxicity still needs to be clarified. In this study, we observed that IGF-1 can salvage the hippocampal neurons in an autophagy-independent manner after 150-μM NMDA exposure using thiazolyl blue tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Western blot assay, and transmission electron microscopy. In addition, over-activation of post-synaptic NMDARs was found with the whole-cell patch clamp recording method. In order to explore whether there is a positive feedback way for post-synaptic NMDARs and the different pathway caused by 150 μM NMDA, the phosphorylation level of Fyn and the phosphorylation site of NR2B were investigated. It was observed that NR2B p-Tyr1472 was increased by the activation of Fyn after 150-μM NMDA exposure. When the neutralizing antibody against NR2B p-Ser1303 was added into the medium, both the activations of Fyn and NR2B p-Tyr1472 were blocked, suggesting NR2B p-Ser1303 may be the initial step of NMDA-induced excitotoxicity. In addition, since IGF-1 can block the initial step of NR2B activation, its effect is concluded to continue with the development of excitotoxicity. Overall, this study strongly indicates that the relationship between different phosphorylation sites of NR2B should be laid more emphasis on, which may be a vital target for the NR2B-involved excitotoxicity.

NeuroQuiz

DEFF Research Database (Denmark)

Brent, Mikkel Bo; Emmanuel, Thomas

2016-01-01

NeuroQuiz er en quiz-app udviklet til neuroanatomi. Den består af mere end 1500 spørgsmål og over 350 anatomiske billeder. Alle spørgsmål tager udgangspunkt i lærebogen Neuroanatomi af Carsten Reidies Bjarkam.......NeuroQuiz er en quiz-app udviklet til neuroanatomi. Den består af mere end 1500 spørgsmål og over 350 anatomiske billeder. Alle spørgsmål tager udgangspunkt i lærebogen Neuroanatomi af Carsten Reidies Bjarkam....

An Aid to Neuro-Ophthalmology

OpenAIRE

Akram, Muhammad

2011-01-01

Muhammad Shoaib AkramDepartment of Ophthalmology, King Fahad Military Hospital, Khamis Mushyat, Saudi ArabiaNeuro-ophthalmology is a very interesting field. Localizing a lesion in various pathways can be challenging, particularly for beginners. One needs a solid foundation of the neuro-anatomy of visual pathways to enhance understanding. The author aims to provide medical students and residents with the basic concepts of neuro-ophthalmology. This text attempts to simplify the complex problems...

Mathematical Modeling of Neuro-Vascular Coupling in Rat Cerebellum

DEFF Research Database (Denmark)

Rasmussen, Tina

Activity in the neurons called climbing fibers causes blood flow changes. But the physiological mechanisms which mediate the coupling are not well understood. This PhD thesis investigates the mechanisms of neuro-vascular coupling by means of mathematical methods. In experiments, the extracellularly...... measured field potential is used as an indicator of neuronal activity, and the cortical blood flow is measured by means of laser-Doppler flowmetry. Using system identification methods, these measurements have been used to construct and validate parametric mathematical models of the neuro-vascular system...

Neuro degenerative diseases: clinical concerns; Les maladies neuro-degeneratives: problemes cliniques

Energy Technology Data Exchange (ETDEWEB)

Ibanez, V. [Hopitaux Universitaires de Geneve (HUG), Unite de Neuroimagerie, Dept. de Psychiatrie (Switzerland)

2005-04-15

Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [{sup 18}F]-deoxyglucose and [{sup 18}F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [{sup 18}F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [{sup 18}F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

Adaptive Neuro-Fuzzy Modeling of UH-60A Pilot Vibration

Science.gov (United States)

Kottapalli, Sesi; Malki, Heidar A.; Langari, Reza

2003-01-01

Adaptive neuro-fuzzy relationships have been developed to model the UH-60A Black Hawk pilot floor vertical vibration. A 200 point database that approximates the entire UH-60A helicopter flight envelope is used for training and testing purposes. The NASA/Army Airloads Program flight test database was the source of the 200 point database. The present study is conducted in two parts. The first part involves level flight conditions and the second part involves the entire (200 point) database including maneuver conditions. The results show that a neuro-fuzzy model can successfully predict the pilot vibration. Also, it is found that the training phase of this neuro-fuzzy model takes only two or three iterations to converge for most cases. Thus, the proposed approach produces a potentially viable model for real-time implementation.

The Importance of the Brain Neuro-Programming Technologies in National and Regional Security

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Vasyl H. Fatkhutdinov

2018-02-01

Full Text Available The authors’ understanding of neuro-programming is the result of the impact on the human brain of information and communication technology (including educational one, through which in the human brain the programs of manifestation in the ontogenesis of internal creative potentials are written. This article summarizes the history of the formation of key neuro-programming technologies of the human brain as well as proves that the changes in the society’s worldview are caused by the possibilities and quality of neuro-programming technologies that society uses. Having influence over worldview stereotypes and behaviour set by the society, neuro-programming technologies essentially ensure the national security of any state and the peaceful coexistence of states in the regions and on the planet as a whole. Using historical and philosophical methods, methods of conceptualization, systematization, modeling, etc., the authors have come to the conclusion that the modern world lies in a confrontation of security strategies, in which neuro-programming technologies play a key role.

The Danish Neuro-Oncology Registry

DEFF Research Database (Denmark)

Hansen, Steinbjørn

2016-01-01

AIM OF DATABASE: The Danish Neuro-Oncology Registry (DNOR) was established by the Danish Neuro-Oncology Group as a national clinical database. It was established for the purpose of supporting research and development in adult patients with primary brain tumors in Denmark. STUDY POPULATION: DNOR has...... advantage of reporting indicators is the related multidisciplinary discussions giving a better understanding of what actually is going on, thereby facilitating the work on adjusting the national guidelines in the Danish Neuro-Oncology Group. CONCLUSION: The establishment of DNOR has optimized the quality...

Therapeutic potential of fecal microbiota transplantation

NARCIS (Netherlands)

Smits, Loek P.; Bouter, Kristien E. C.; de Vos, Willem M.; Borody, Thomas J.; Nieuwdorp, Max

2013-01-01

There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal

The endocannabinoid anandamide regulates the peristaltic reflex by reducing neuro-neuronal and neuro-muscular neurotransmission in ascending myenteric reflex pathways in rats.

Science.gov (United States)

Sibaev, Andrei; Yuece, Birol; Allescher, Hans Dieter; Saur, Dieter; Storr, Martin; Kurjak, Manfred

2014-04-01

Endocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are involved in the regulation of motility in the gastrointestinal (GI) tract. However, the underlying physiological mechanisms are not completely resolved. The purpose of this work was to study the physiological influence of the endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and of the CB1 receptor on ascending peristaltic activity and to identify the involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms. The effects of anandamide and the CB1 receptor antagonist SR141716A were investigated on contractions of the circular smooth muscle of rat ileum and in longitudinal rat ileum segments where the ascending myenteric part of the peristaltic reflex was studied in a newly designed organ bath. Additionally intracellular recordings were performed in ileum and colon. Anandamide significantly reduced cholinergic twitch contractions of ileum smooth muscle whereas SR141716A caused an increase. Anandamide reduced the ascending peristaltic contraction by affecting neuro-neuronal and neuro-muscular neurotransmission. SR141716A showed opposite effects and all anandamide effects were antagonized by SR141716A (1 μM). Anandamide reduced excitatory junction potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal slow waves were not affected. CB1 receptors regulate force and timing of the intestinal peristaltic reflex and these actions involve interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates these effects by activation of CB1 receptors. The endogenous cannabinoid system is permanently active, suggesting the CB1 receptor being a possible target for the treatment of motility related disorders. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The human resource crisis in neuro-ophthalmology.

Science.gov (United States)

Frohman, Larry P

2008-09-01

Neuro-ophthalmology is facing a serious human resource issue. Few are entering the subspecialty, which is perceived as being poorly compensated compared with other subspecialties of ophthalmology. The low compensation comes from the fact that 1) non-procedural encounters remain undervalued, 2) efforts that benefit other medical specialists are not counted, and 3) the relatively low expenses of neuro-ophthalmologists are not factored into compensation formulas. Mission-based budgeting, which forces academic departments to be financially accountable without the expectation of fiscal relief from medical schools or practice plans, has exacerbated the compensation issue. Solutions must come from within neuro-ophthalmology, academic departments, medical schools, and medical practice plans. They include 1) providing educational resources so that neuro-ophthalmologists need not spend so much time teaching the basics, 2) factoring into compensation the impact of neuro-ophthalmologists in teaching and on revenue generation by procedure-based specialists, 3) improving the efficiency of neuro-ophthalmologists in their consultative practices by providing ample clerical support and other measures, 4) providing contractual salary compensation by departments such as neurosurgery to recognize the contributions made by neuro-ophthalmologists, and 5) reorganizing the academic clinical effort as multidisciplinary rather than departmental.

Inflammatory bowel disease: potential therapeutic strategies

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Bregenholt, S

1997-01-01

This review deals with potential and possibly primary therapeutics that, through insight into the inflammatory cascade, result in more rational treatment principles replacing the classical therapy of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). These ne...

The clinical neuro-ophthalmology of vision

International Nuclear Information System (INIS)

Kashii, Satoshi

2008-01-01

To diagnose a patient with a failing visual system, it is necessary to localize the site of the lesion in the system, and identify the etiology that has produced it. Physicians do not see diseases but just their manifestations. Clinical neuro-ophthalmology provides the basic principles on how to progress from manifestations to the diseases they indicate. The Frank B. Walsh Neuro-Ophthalmology Society (the Walsh Society) that originated in 1969 in the United States has been the center of clinical neuro-ophthalmology case studies throughout the world. In Japan, the Ronald M. Burde Clinical Neuro-Ophthalmology Study Group (the RMB Society) was organized in 2001 to establish and promote a clinicopathologic conference in the style of the Walsh Society. On this occasion, Prof. Burde was invited to the Annual Japanese Ophthalmological Society meeting. Based on some illustrative cases presented at the annual meetings of the RMB society, this review was carried out to present the current knowledge of clinical neuro-ophthalmology. (author)

A Profile of Neuro-Ophthalmic Practice Around the World.

Science.gov (United States)

Frohman, Larry P

2018-03-01

To compare contrast neuro-ophthalmic practice in various countries, an 18-question survey was sent to the international North American Neuro-Ophthalmology Society (NANOS) members in the spring of 2016. At least 1 NANOS member was contacted for each non-US nation in the NANOS membership roster. If there were multiple NANOS members from 1 country, multiple were contacted. If responses were received from more than 1 person from a single country, the first response received was used as the source data. The survey (in English) was emailed to 47 NANOS members from 31 countries. Twenty responses were received representing members from 15 nations. In all 15 nations, at least half of the neuro-ophthalmologists were trained as ophthalmologists. In 60% of nations, at least half of the neuro-ophthalmologists were trained internally, whereas in 33% of countries, at least half were trained in the United States. The number of physicians who practiced a significant amount of neuro-ophthalmology ranged from low (0.08/million, India) to high (3.10/million, Israel). Countries having the highest percentage of neuro-ophthalmologists exclusively practicing neuro-ophthalmology also were those with better patient access to neuro-ophthalmic care. Requirement of approval to see a neuro-ophthalmologist or for imaging studies requested by neuro-ophthalmologists was not typical. In most nations, academic neuro-ophthalmologists were paid a straight salary. In no nation were neuro-ophthalmologists paid more than another ophthalmic subspecialty. Individual national health care system designs and compensation models have had a profound influence on the rewards and challenges that face neuro-ophthalmologists. There seems to have been a connection between recognition of the discipline, financial rewards of neuro-ophthalmic practice, conditions that permit full-time neuro-ophthalmic practice, and patient access to care. A higher percentage of gross national product for health care did not seem to

Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality

Directory of Open Access Journals (Sweden)

Senija Selimovic-Hamza

2017-01-01

Full Text Available Next-generation sequencing (NGS has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections.

NeuroManager: A workflow analysis based simulation management engine for computational neuroscience

Directory of Open Access Journals (Sweden)

David Bruce Stockton

2015-10-01

Full Text Available We developed NeuroManager, an object-oriented simulation management software engine for computational neuroscience. NeuroManager automates the workflow of simulation job submissions when using heterogeneous computational resources, simulators, and simulation tasks. The object-oriented approach 1 provides flexibility to adapt to a variety of neuroscience simulators, 2 simplifies the use of heterogeneous computational resources, from desktops to super computer clusters, and 3 improves tracking of simulator/simulation evolution. We implemented NeuroManager in Matlab, a widely used engineering and scientific language, for its signal and image processing tools, prevalence in electrophysiology analysis, and increasing use in college Biology education. To design and develop NeuroManager we analyzed the workflow of simulation submission for a variety of simulators, operating systems, and computational resources, including the handling of input parameters, data, models, results, and analyses. This resulted in twenty-two stages of simulation submission workflow. The software incorporates progress notification, automatic organization, labeling, and time-stamping of data and results, and integrated access to Matlab's analysis and visualization tools. NeuroManager provides users with the tools to automate daily tasks, and assists principal investigators in tracking and recreating the evolution of research projects performed by multiple people. Overall, NeuroManager provides the infrastructure needed to improve workflow, manage multiple simultaneous simulations, and maintain provenance of the potentially large amounts of data produced during the course of a research project.

Cyclic peptides as potential therapeutic agents for skin disorders.

Science.gov (United States)

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

NeuroMorpho

Data.gov (United States)

U.S. Department of Health & Human Services — NeuroMorpho.Org is a centrally curated inventory of digitally reconstructed neurons associated with peer-reviewed publications. It contains contributions from over...

Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

Directory of Open Access Journals (Sweden)

Marina Rubio

Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

A neuro-fuzzy inference system for sensor monitoring

International Nuclear Information System (INIS)

Na, Man Gyun

2001-01-01

A neuro-fuzzy inference system combined with the wavelet denoising, PCA (principal component analysis) and SPRT (sequential probability ratio test) methods has been developed to monitor the relevant sensor using the information of other sensors. The paramters of the neuro-fuzzy inference system which estimates the relevant sensor signal are optimized by a genetic algorithm and a least-squares algorithm. The wavelet denoising technique was applied to remove noise components in input signals into the neuro-fuzzy system. By reducing the dimension of an input space into the neuro-fuzzy system without losing a significant amount of information, the PCA was used to reduce the time necessary to train the neuro-fuzzy system, simplify the structure of the neuro-fuzzy inference system and also, make easy the selection of the input signals into the neuro-fuzzy system. By using the residual signals between the estimated signals and the measured signals, the SPRT is applied to detect whether the sensors are degraded or not. The proposed sensor-monitoring algorithm was verified through applications to the pressurizer water level, the pressurizer pressure, and the hot-leg temperature sensors in pressurized water reactors

Potential application of lithium in Parkinson’s and other neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Carol A Lazzara

2015-10-01

Full Text Available Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson’s disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of Calpain-1. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

A neuro-immune, neuro-oxidative and neuro-nitrosative model of prenatal and postpartum depression.

Science.gov (United States)

Roomruangwong, Chutima; Anderson, George; Berk, Michael; Stoyanov, Drozdstoy; Carvalho, André F; Maes, Michael

2018-02-02

A large body of evidence indicates that major affective disorders are accompanied by activated neuro-immune, neuro-oxidative and neuro-nitrosative stress (IO&NS) pathways. Postpartum depression is predicted by end of term prenatal depressive symptoms whilst a lifetime history of mood disorders appears to increase the risk for both prenatal and postpartum depression. This review provides a critical appraisal of available evidence linking IO&NS pathways to prenatal and postpartum depression. The electronic databases Google Scholar, PubMed and Scopus were sources for this narrative review focusing on keywords, including perinatal depression, (auto)immune, inflammation, oxidative, nitric oxide, nitrosative, tryptophan catabolites (TRYCATs), kynurenine, leaky gut and microbiome. Prenatal depressive symptoms are associated with exaggerated pregnancy-specific changes in IO&NS pathways, including increased C-reactive protein, advanced oxidation protein products and nitric oxide metabolites, lowered antioxidant levels, such as zinc, as well as lowered regulatory IgM-mediated autoimmune responses. The latter pathways coupled with lowered levels of endogenous anti-inflammatory compounds, including ω3 polyunsaturated fatty acids, may also underpin the pathophysiology of postpartum depression. Although increased bacterial translocation, lipid peroxidation and TRYCAT pathway activation play a role in mood disorders, similar changes do not appear to be relevant in perinatal depression. Some IO&NS biomarker characteristics of mood disorders are found in prenatal depression indicating that these pathways partly contribute to the association of a lifetime history of mood disorders and perinatal depression. However, available evidence suggests that some IO&NS pathways differ significantly between perinatal depression and mood disorders in general. This review provides a new IO&NS model of prenatal and postpartum depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Radioisotopic Imaging of Neuro-inflammation

International Nuclear Information System (INIS)

Winkeler, A.; Boisgard, R.; Martin, M.; Tavitian, B.

2010-01-01

Inflammatory responses are closely associated with many neurologic disorders and influence their outcome. In vivo imaging can document events accompanying neuro-inflammation, such as changes in blood flow, vascular permeability, tightness of the blood-to-brain barrier, local metabolic activity, and expression of specific molecular targets. Here, we briefly review current methods for imaging neuro-inflammation, with special emphasis on nuclear imaging techniques. (authors)

Psycho-Neuro-Endocrine-Immunology: A Psychobiological Concept.

Science.gov (United States)

França, Katlein; Lotti, Torello M

2017-01-01

Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) is a scientific field of study that investigates the link between bidirectional communications among the nervous system, the endocrine system, and the immune system and the correlations of this cross-talk with physical health. The P.N.E.I. innovative medical approach represents a paradigm shift from a strictly biomedical view of health and disease taken as hermetically sealed compartments to a more interdisciplinary one. The key element of P.N.E.I. approach is represented by the concept of bidirectional cross-talk between the psychoneuroendocrine and immune systems. The Low Dose Medicine is one of the most promising approaches able to allow the researchers to design innovative therapeutic strategies for the treatment of skin diseases based on the rebalance of the immune response.

Protection of neurons in the retinal ganglion cell layer against excitotoxicity by the N-acylethanolamine, N-linoleoylethanolamine

Directory of Open Access Journals (Sweden)

Duncan RS

2011-04-01

Full Text Available R. Scott Duncan1,*, Hua Xin1,*, Daryl L Goad1, Kent D Chapman2,3, Peter Koulen1,31Vision Research Center and Departments of Ophthalmology and Basic Medical Science, School of Medicine, University of Missouri, Kansas City, MO, USA; 2Department of Biological Sciences, University of North Texas, Denton, TX, USA; 3Center for Plant Lipid Research, University of North Texas, Denton, TX, USA *Authors contributed equallyAbstract: Retinal ganglion cell (RGC death is a hallmark of neurodegenerative diseases and disease processes of the eye, including glaucoma. The protection of RGCs has been an important strategy for combating glaucoma, but little clinical success has been reported to date. One pathophysiological consequence of glaucoma is excessive extracellular glutamate subsequently leading to excitotoxicity in the retina. Endocannabinoids, such as the N-acylethanolamine (NAE, arachidonylethanolamine (NAE 20:4, exhibit neuroprotective properties in some models of neurodegenerative disease. The majority of NAEs, however, are not cannabinoids, and their physiological function is not clear. Here, we determined whether the noncannabinoid NAE, linoleoylethanolamine (NAE18:2, protects neurons in the RGC layer against glutamate excitotoxicity in ex-vivo retina cultures. Using a terminal deoxynucleotidyl transferase-mediated dUTP (2´-deoxyuridine 5´-triphosphate nick-end labeling (TUNEL assay, we determined that NAE18:2 reduces the number of apoptotic RGC layer neurons in response to glutamate and conclude that NAE18:2 is a neuroprotective compound with potential for treating glaucomatous retinopathy.Keywords: neuroprotection, glutamate, calcium signaling, immunocytochemistry, eye, vision, glaucoma.

[To strengthen the education on basic knowledge and skills of neuro-ophthalmology].

Science.gov (United States)

Zhang, Xiao-jun; Wang, Ning-li

2011-12-01

Basic knowledge and skills are cornerstone of the diagnosis and treatment of neuro-ophthalmology diseases in ophthalmology practice. Due to the interdisciplinary features of neuro-ophthalmology, neuro-anatomy, neuro-physiology related to eyes, neuro-image and neuro-electrodiagnosis, these should be included in the education for the ophthalmologist. Special attention should be paid to training on capability of logically thinking in neuro-ophthalmology. Multiple ways can be used for the education of ophthalmologists and neurologists for the enhancement of basic knowledge and skills of neuro-ophthalmology in China.

Neuro degenerative diseases: clinical concerns

International Nuclear Information System (INIS)

Ibanez, V.

2005-01-01

Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [ 18 F]-deoxyglucose and [ 18 F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [ 18 F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [ 18 F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

Neuroprotection by delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Stelt, M. van der; Veldhuis, W.B.; Bär, P.R; Veldink, G.A.; Nicolay, K.

2001-01-01

Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that delta9-tetrahydrocannabinol (delta9-THC), the main active compound in

The Nasal Route as a Potential Pathway for Delivery of Erythropoietin in the Treatment of Acute Ischemic Stroke in Humans

Directory of Open Access Journals (Sweden)

Julio Cesar García-Rodríguez

2009-01-01

Full Text Available Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB in order to deliver therapeutic agents to the brain. This method allows drugs that do not cross the BBB to be delivered to the central nervous system in a few minutes. With this technology, it will be possible to eliminate systemic administration and its potential side effects. Using the intranasal delivery system, researchers have demonstrated neuroprotective effects in different animal models of stroke using erythropoietin (EPO as a neuroprotector or other different types of EPO without erythropoiesis-stimulating activity. These new molecules retain their ability to protect neural tissue against injury and they include Asialoerythropoietin (asialoEPO carbamylated EPO (CEPO, and rHu-EPO with low sialic acid content (Neuro-EPO. Contrary to the other EPO variants, Neuro-EPO is not chemically modified, making it biologically similar to endogenous EPO, with the advantage of less adverse reactions when this molecule is applied chronically. This constitutes a potential benefit of Neuro-EPO over other variants of EPO for the chronic treatment of neurodegenerative illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic approach. However, it will be necessary to initiate clinical trials in stroke patients using intranasal delivery in order to obtain the clinical evidence of its neuroprotectant capacity in the treatment of patients with acute stroke and other neurodegenerative disorders. This new therapeutic approach could revolutionize the treatment of neurodegenerative disorders in the 21st century.

Single-Cell Imaging of Bioenergetic Responses to Neuronal Excitotoxicity and Oxygen and Glucose Deprivation

OpenAIRE

Connolly, Niamh M; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen HM

2014-01-01

Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca2+/Na+ influx into neurons, energetic stress, and subsequent neuronal injury.We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contributio...

Magnetic resonance imaging in neuro-Behcet's disease

International Nuclear Information System (INIS)

Kojima, Shigeyuki; Fukutake, Toshio; Hirayama, Keizo; Iwamoto, Itsuo

1987-01-01

In four patients with neuro-Behcet's disease, the findings of magnetic resonance imaging (MRI) were evaluated in comparison with the results of X-ray computed tomography (CT), especially for brainstem lesions. MRI was able to reveal brainstem lesions in three patients, in addition to lesions of basal ganglia, internal capsule and thalamus in the same patients. In contrast, X-ray CT demonstrated lesions of basal ganglia and internal capsule in only one patient, and it did not detect any brainstem lesions. Non-specific findings, including cerebral and brainstem atrophy, were revealed more clearly in inversion recovery images than in X-ray CT. Spin echo images were superior to inversion recovery images for detecting the lesions of demyelination, necrosis, gliosis and so on in neuro-Behcet's disease. The brainstem lesions visualized by MRI were situated in the regions of the basis pontis, cerebral peduncle and tectum of the midbrain. In neuro-Behcet's disease, the main pathological lesions are known occur in the ventral parts of the brainstem, but X-ray CT cannot always reveale these brainstem lesions because it produces bone artifacts. For this reason, the X-ray CT findings of neuro-Behcet's disease reported previously have been nonspecific cerebral or brainstem atrophy and decreased attenuations in the basal ganglia or subcortical white matter. Thus it is generally difficult to differentiate neuro-Behcet's disease from other intracranial lesions on the basis of the supratentorial X-ray CT findings. However, the above mentioned brainstem lesions visualized by MRI are consistent with the pathologically preferential site in neuro-Behcet's disease, and MRI can assist in the clinical diagnosis of neuro-Behcet's disease by demonstrating the brainstem lesions clearly, even when neurological involvement precedes the typical dermatologic and ophthalmologic manifestations. (author)

Neuroprotection by Δ9-Tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity

NARCIS (Netherlands)

Stelt, van der M.; Veldhuis, W.B.; Bär, P.R.; Veldink, G.A.; Vliegenthart, J.F.G.; Nicolaij, K.

2001-01-01

Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that ¿9-tetrahydrocannabinol (¿9-THC), the main active compound in marijuana,

Updates from the 2013 Society for Neuro-Oncology annual and World Federation for Neuro-Oncology quadrennial meeting.

Science.gov (United States)

Lukas, Rimas V; Amidei, Christina

2014-01-01

We present an overview of a number of key clinical studies in infiltrating gliomas presented at the 2013 Society for Neuro-Oncology and World Federation of Neuro-Oncology joint meeting. This review focuses on efficacy results, including quality of life studies, from larger clinical trials in both high- and low-grade infiltrating gliomas.

2nd International Conference on NeuroRehabilitation

CERN Document Server

Andersen, Ole; Akay, Metin

2014-01-01

The book is the proceedings of the 2nd International Conference on NeuroRehabilitation (ICNR 2014), held 24th-26th June 2014 in Aalborg, Denmark. The conference featured the latest highlights in the emerging and interdisciplinary field of neural rehabilitation engineering and identified important healthcare challenges the scientific community will be faced with in the coming years. Edited and written by leading experts in the field, the book includes keynote papers, regular conference papers, and contributions to special and innovation sessions, covering the following main topics: neuro-rehabilitation applications and solutions for restoring impaired neurological functions; cutting-edge technologies and methods in neuro-rehabilitation; and translational challenges in neuro-rehabilitation. Thanks to its highly interdisciplinary approach, the book will not only be a  highly relevant reference guide for academic researchers, engineers, neurophysiologists, neuroscientists, physicians and physiotherapists workin...

From ‘Hard’ Neuro-Tools to ‘Soft’ Neuro-Toys? : Refocussing the Neuro-Enhancement Debate

NARCIS (Netherlands)

Brenninkmeijer, Jonna; Zwart, Hub

2016-01-01

Since the 1990’s, the debate concerning the ethical, legal and societal aspects of ‘neuro-enhancement’ has evolved into a massive discourse, both in the public realm and in the academic arena. This ethical debate, however, tends to repeat the same sets of arguments over and over again. Normative

Therapeutic potential of cannabis-related drugs.

Science.gov (United States)

Alexander, Stephen P H

2016-01-04

In this review, I will consider the dual nature of Cannabis and cannabinoids. The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every other medicinal drug of course, the 'trick' will be to maximise the benefit and minimise the cost. After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuro-epistemology: a post-modernist analysis of the neuro ...

African Journals Online (AJOL)

This paper examines the theoretical framework in which we construct our terms of reference when examining patients from an integrated Meyerian biopsychosocial perspective. We coin the term iยDneuro-epistemologylo, defining the frame for scientific inquiry into the nature and status of knowledge in neuro-sciences, ...

The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

DEFF Research Database (Denmark)

Olsen, Lars Rønn

or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... of genomics and proteomics, and clinical studies need to be combined. These analyses produce large amounts of data that require advanced bioinformatics methods for collection, management, integration and interpretation. In this thesis, I have explored the potential of tumor antigens as biomarkers...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

Clinical Relevance of Steroid Use in Neuro-Oncology.

Science.gov (United States)

Ly, K Ina; Wen, Patrick Y

2017-01-01

Corticosteroids are commonly used in the management of primary central nervous system (CNS) tumors and CNS metastases to treat cancer- and treatment-related cerebral edema and improve neurologic function. However, they are also associated with significant morbidity and mortality, given their wide range of adverse effects. To review the mechanism of action, pharmacology, and toxicity profile of corticosteroids and to critically appraise the evidence that supports their use in neuro-oncologic practice based on the latest scientific and clinical data. Recent data suggest that corticosteroids may negatively impact survival in glioma patients. In addition, corticosteroids should be incorporated as a standard criterion to assess a patient's clinical and radiographic response to treatment. Corticosteroids should be used judiciously in neuro-oncologic patients, given the potential deleterious effects on clinical outcome and patient survival. Anti-angiogenic agents, which lack these adverse effects, may be a reasonable alternative to corticosteroids.

Randomized, multicenter, comparative study of NEURO versus CIMT in poststroke patients with upper limb hemiparesis: the NEURO-VERIFY Study.

Science.gov (United States)

Abo, Masahiro; Kakuda, Wataru; Momosaki, Ryo; Harashima, Hiroaki; Kojima, Miki; Watanabe, Shigeto; Sato, Toshihiro; Yokoi, Aki; Umemori, Takuma; Sasanuma, Jinichi

2014-07-01

Many poststroke patients suffer functional motor limitation of the affected upper limb, which is associated with diminished health-related quality of life. The aim of this study is to conduct a randomized, multicenter, comparative study of low-frequency repetitive transcranial magnetic stimulation combined with intensive occupational therapy, NEURO (NovEl intervention Using Repetitive TMS and intensive Occupational therapy) versus constraint-induced movement therapy in poststroke patients with upper limb hemiparesis. In this randomized controlled study of NEURO and constraint-induced movement therapy, 66 poststroke patients with upper limb hemiparesis were randomly assigned at 2:1 ratio to low-frequency repetitive transcranial magnetic stimulation plus occupational therapy (NEURO group) or constraint-induced movement therapy (constraint-induced movement therapy group) for 15 days. Fugl-Meyer Assessment and Wolf Motor Function Test and Functional Ability Score of Wolf Motor Function Test were used for assessment. No differences in patients' characteristics were found between the two groups at baseline. The Fugl-Meyer Assessment score was significantly higher in both groups after the 15-day treatment compared with the baseline. Changes in Fugl-Meyer Assessment scores and Functional Ability Score of Wolf Motor Function Test were significantly higher in the NEURO group than in the constraint-induced movement therapy group, whereas the decrease in the Wolf Motor Function Test log performance time was comparable between the two groups (changes in Fugl-Meyer Assessment score, NEURO: 5·39 ± 4·28, constraint-induced movement therapy: 3·09 ± 4·50 points; mean ± standard error of the mean; P < 0·05) (changes in Functional Ability Score of Wolf Motor Function Test, NEURO: 3·98 ± 2·99, constraint-induced movement therapy: 2·09 ± 2·96 points; P < 0·05). The results of the 15-day rehabilitative protocol showed the superiority of NEURO

A neuro-fuzzy computing technique for modeling hydrological time series

Science.gov (United States)

Nayak, P. C.; Sudheer, K. P.; Rangan, D. M.; Ramasastri, K. S.

2004-05-01

Intelligent computing tools such as artificial neural network (ANN) and fuzzy logic approaches are proven to be efficient when applied individually to a variety of problems. Recently there has been a growing interest in combining both these approaches, and as a result, neuro-fuzzy computing techniques have evolved. This approach has been tested and evaluated in the field of signal processing and related areas, but researchers have only begun evaluating the potential of this neuro-fuzzy hybrid approach in hydrologic modeling studies. This paper presents the application of an adaptive neuro fuzzy inference system (ANFIS) to hydrologic time series modeling, and is illustrated by an application to model the river flow of Baitarani River in Orissa state, India. An introduction to the ANFIS modeling approach is also presented. The advantage of the method is that it does not require the model structure to be known a priori, in contrast to most of the time series modeling techniques. The results showed that the ANFIS forecasted flow series preserves the statistical properties of the original flow series. The model showed good performance in terms of various statistical indices. The results are highly promising, and a comparative analysis suggests that the proposed modeling approach outperforms ANNs and other traditional time series models in terms of computational speed, forecast errors, efficiency, peak flow estimation etc. It was observed that the ANFIS model preserves the potential of the ANN approach fully, and eases the model building process.

Ayahuasca: Pharmacology, neuroscience and therapeutic potential.

Science.gov (United States)

Domínguez-Clavé, Elisabet; Soler, Joaquim; Elices, Matilde; Pascual, Juan C; Álvarez, Enrique; de la Fuente Revenga, Mario; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi

2016-09-01

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT 2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one's own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Exosomes and Their Therapeutic Potentials of Stem Cells

Directory of Open Access Journals (Sweden)

Chao Han

2016-01-01

Full Text Available Exosomes, a group of vesicles originating from the multivesicular bodies (MVBs, are released into the extracellular space when MVBs fuse with the plasma membrane. Numerous studies indicate that exosomes play important roles in cell-to-cell communication, and exosomes from specific cell types and conditions display multiple functions such as exerting positive effects on regeneration in many tissues. It is widely accepted that the therapeutic potential of stem cells may be mediated largely by the paracrine factors, so harnessing the paracrine effects of stem and progenitor cells without affecting these living, replicating, and potentially pluripotent cell populations is an advantage in terms of safety and complexity. Ascending evidence indicated that exosomes might be the main components of paracrine factors; thus, understanding the role of exosomes in each subtype of stem cells is far-reaching. In this review, we discuss the functions of exosomes from different types of stem cells and emphasize the therapeutic potentials of exosomes, providing an alternative way of developing strategies to cure diseases.

Heidelberg Neuro-Music Therapy for chronic-tonal tinnitus - treatment outline and psychometric evaluation.

Science.gov (United States)

Argstatter, Heike; Grapp, Miriam; Plinkert, Peter K; Bolay, Hans Volker

2012-01-01

Musical training positively influences the cortical plasticity of the brain and has proven to be effective in treating chronic tinnitus. A neuro-music therapy concept, the "Heidelberg Neuro-Music Therapy" treatment was developed and evaluated. A prospective, cross-sectional design was used. N = 135 patients (mean age 47 years) with chronic, tonal tinnitus attended a standardized protocol for Neuro-Music Therapy (either "standard therapy" ST or "compact therapy" CT). The results were compared to a cognitive behavioral placebo music therapy procedure (PT). Tinnitus distress was assessed using the German version of the Tinnitus-Questionnaire (TQ) at admission, at discharge and six months after therapy. Changes were assessed statistically and by means of clinical significance. TQ scores significantly improved - independent of group allocation. But more than 80% of the music therapy patients (both ST and CT) revealed a reliable improvement ("responder") compared to 44% in the PT group. Therapy impact seems to be lasting since TQ scores remained stable until follow-up at six months. The "Heidelberg Neuro-Music Therapy" is a method with fast onset and long lasting effect for patients with "tonal" tinnitus. A number of potential working factors accounting for the treatment success are highlighted.

Significance of head CT in neuro-ophthalmology

International Nuclear Information System (INIS)

Nishimoto, Yuichiro; Masuyama, Yoshimasa; Nakamura, Yasuko; Fujimoto, Toshiro.

1979-01-01

It is important to perform CT purposefully in patients with some neuro-ophthalmological disorders. Using Hitachi CT-H250 with the finer matrix of 256 x 256 and a section thickness of 5 mm and 10 mm, we performed head CT in 98 patients with various kinds of neuro-ophthalmological disorders in these 30 months. Neuro-ophthalmological findings in these patients were visual disturbance, visual field defects (hemianopsia, quandrantanopsia, enlargement of the blind spot, central scotoma), papilledema, optic nerve atrophy, difficulties in ocular movements, and others. In 44 (44.9%) of these 98 patients, abnormal findings were displayed in the head CT, characterizing intracranial tumors, intracranial infarction, aneurysms in intracranial vessels, arterio-venous malformation, enlargement of the ventricle or the cistern. In some cases the head CT was the decisive procedure in ensuring a correct diagnosis. We presented findings in the head CT in several interesting cases. We recognized the necessity of the head CT in patients with neuro-ophthalmological disorders. (author)

Accelerating Translational Research through Open Science: The Neuro Experiment.

Science.gov (United States)

Gold, E Richard

2016-12-01

Translational research is often afflicted by a fundamental problem: a limited understanding of disease mechanisms prevents effective targeting of new treatments. Seeking to accelerate research advances and reimagine its role in the community, the Montreal Neurological Institute (Neuro) announced in the spring of 2016 that it is launching a five-year experiment during which it will adopt Open Science-open data, open materials, and no patenting-across the institution. The experiment seeks to examine two hypotheses. The first is whether the Neuro's Open Science initiative will attract new private partners. The second hypothesis is that the Neuro's institution-based approach will draw companies to the Montreal region, where the Neuro is based, leading to the creation of a local knowledge hub. This article explores why these hypotheses are likely to be true and describes the Neuro's approach to exploring them.

Accelerating Translational Research through Open Science: The Neuro Experiment.

Directory of Open Access Journals (Sweden)

E Richard Gold

2016-12-01

Full Text Available Translational research is often afflicted by a fundamental problem: a limited understanding of disease mechanisms prevents effective targeting of new treatments. Seeking to accelerate research advances and reimagine its role in the community, the Montreal Neurological Institute (Neuro announced in the spring of 2016 that it is launching a five-year experiment during which it will adopt Open Science-open data, open materials, and no patenting-across the institution. The experiment seeks to examine two hypotheses. The first is whether the Neuro's Open Science initiative will attract new private partners. The second hypothesis is that the Neuro's institution-based approach will draw companies to the Montreal region, where the Neuro is based, leading to the creation of a local knowledge hub. This article explores why these hypotheses are likely to be true and describes the Neuro's approach to exploring them.

Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

International Nuclear Information System (INIS)

Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

2007-01-01

It has been six decades since synthesis of organophosphates, but this chapter has not yet come to a closure. Toxic effects of organophosphates are well known and the current therapeutic scheme includes supportive therapy and antidotes. There is a dilemma on whether and when to apply gastric lavage and activated charcoal. According to Position Statement (by EAPCCT) it should be applied only if the patient presents within one hour of ingestion, with potentially lethal ingested dose. Atropine, a competitive antagonist of acetylcholine at m-receptors, which antagonizes bronchosecretion and bronchoconstriction, is the corner stone of acute organophosphate poisoning therapy. There were many attempts to find a more efficient drug, including glycopyrrolate which has been used even in clinical trials, but it still can not replace atropine. The only dilemma about atropine usage which still exists, concerns usage of high atropine dose and scheme of application. The most efficient atropinization is achieved with bolus doses of 1-2mg of atropine i.v push, with repeating the dose on each 5 minutes until signs of atropinization are registered. Diazepam, with its GABA stabilizing effect, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated acetylcholinesterase, which still has not gone ageing, reducing acetylcholine concentration and cholinergic crisis. These effects are clearly demonstrated in experimental conditions, but the clinical significance of oximes is still unclear and there are still those who question oxime therapy. For those who approve it, oxime dosage, duration of therapy, the choice of oxime for certain OP is still an open issue. We need new, more efficient antidotes, and those that are in use are only the small part of the therapy which could be used. Experimental studies show favorable therapeutic effect of many agents, but none of them has been introduced in standard treatment of OPI poisoning in the last 30

Therapeutic potential of stem cells in veterinary practice

Directory of Open Access Journals (Sweden)

Nitin E Gade

Full Text Available Stem cell research acquired great attention during last decade inspite of incredible therapeutic potential of these cells the ethical controversies exists. Stem cells have enormous uses in animal cloning, drug discovery, gene targeting, transgenic production and regenerative therapy. Stem cells are the naïve cells of body which can self-renew and differentiate into other cell types to carry out multiple functions, these properties have been utilized in therapeutic application of stem cells in human and veterinary medicine. The application of stem cells in human medicine is well established and it is commonly used for chronic and accidental injuries. In Veterinary sciences previous studies mostly focused on establishing protocols for isolation and their characterization but with advancement in array of techniques for in vitro studies, stem cells rapidly became a viable tool for regenerative therapy of chronic, debilitating and various unresponsive clinical diseases and disorders. Multipotent adult stem cells have certain advantages over embryonic stem cells like easy isolation and expansion from numerous sources, less immunogenicity and no risk of teratoma formation hence their use is preferred in therapeutics. Adult stem cells have been utilized for treatment of spinal injuries, tendonitis, cartilage defects, osteoarthritis and ligament defects, liver diseases, wounds, cardiac and bone defects in animals. The multi-potential capability of these cells can be better utilized in near future to overcome the challenges faced by the clinicians. This review will emphasize on the therapeutic utilization and success of stem cell therapies in animals. [Vet. World 2012; 5(8.000: 499-507

Positron computed tomography studies: potential use in neuro-psychiatric disorders

International Nuclear Information System (INIS)

Yamasaki, T.; Tateno, Y.; Shishido, F.

1982-01-01

Since November 1979 positron computed tomography (PCT) have been performed to study subjects in a variety of states and varied disorders, using 13 NH 3 , 11 CO and 18 F-2-fluorodeoxyglucose ( 18 FDG) at the National Institute of Radiological Sciences, Japan. In neuro-psychiatric studies, normal volunteers and patients including schizophrenia, affective disorders, Alzheimer's disease, Huntigton's chorea were studied. Tomographic images were analyzed by visual observation and activity counting in regions selected. In degenerative disorder group, 18 FDG revealed decreased accumulation in target areas, whereas in functional psychosis group both in medicating patients and in non-medicated patients, positron images were basically similar to normal controls. Especially in a patient with Huntington's chorea, 18 FDG accumulation in striatal region was markedly decreased without significant change in the same region on X-ray CT and 13 NH 3 PCT

In vivo imaging of neuro-inflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

International Nuclear Information System (INIS)

Chauveau, F.; Boutin, H.; Van Camp, N.; Thominiaux, C.; Dolle, F.; Tavitian, B.; Chauveau, F.; Boutin, H.; Van Camp, N.; Tavitian, B.; Hantraye, P.; Rivron, L.; Marguet, F.; Castel, M.N.; Rooney, T.; Benavides, J.; Chauveau, F.; Boutin, H.

2011-01-01

Purpose Neuro-inflammation is involved in neurological disorders through the activation of micro-glial cells. Imaging of neuro-inflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive bio-marker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N, N, 5- trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino[4, 5-b] indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuro-protective effects. Methods Here we report the radiolabelling of SSR180575 with 11 C and in vitro and in vivo imaging in an acute model of neuro-inflammation in rats. Results The image contrast and the binding of [ 11 C] SSR180575 are higher than that obtained with the isoquinoline- based TSPO radioligand, [ 11 C]PK11195. Competition studies demonstrate that [ 11 C]SSR180575 has high specific binding for the TSPO. Conclusion [ 11 C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuro-inflammation in animal models and in the clinic. (authors)

[Neuro-ophthalmology: the eye as a window to the brain].

Science.gov (United States)

Kesler, Anat

2013-02-01

Neuro-ophthalmology focuses on the diagnosis and treatment of visual disorders related to the neurological system rather than the globe itself. Being a subspecialty of both neurology and ophthalmology, it requires specialized training and expertise in diseases of the eye, brain, nerves and muscles. Commonly encountered pathologies in neuro-ophthalmology include: optic neuropathies (such as optic neuritis and ischemic optic neuropathy), visual field loss (transient, constant, unexplained), transient visual loss, unspecified visual disturbances, diplopia, abnormal eye movements, thyroid eye disease, myasthenia gravis, anisocoria, and eyelid abnormalities. The current issue of "Harefuah" is dedicated to contemporary knowledge in neuro-opthalmology, and spans from studies of neuromyelitis optica (NMO), ischemic optic neuropathies, and optic neuropathies induced by phosphodiesterase inhibitors, to the management of sight-threatening carotid-cavernous fistulas, and more. These studies emphasize the importance of an interdisciplinary treatment team consisting of a neuro-ophthalmologist, a neuro-radiologist, and sometimes, even a neuro-surgeon. Such an approach may prove to be beneficial to the patient, by optimizing follow-up and treatment decisions. This issue emphasizes how a correct and timely diagnosis is of paramount significance in patients with neuro-ophthalmological disorders.

Improving English Instruction through Neuro-Linguistic Programming

Science.gov (United States)

Helm, David Jay

2009-01-01

This study examines the background information and numerous applications of neuro-linguistic programming as it applies to improving English instruction. In addition, the N.L.P. modalities of eye movement, the use of predicates, and posturing are discussed. Neuro-linguistic programming presents all students of English an opportunity to reach their…

Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

Science.gov (United States)

Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

2014-01-01

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

The Danish Neuro-Oncology Registry

DEFF Research Database (Denmark)

Hansen, Steinbjørn; Nielsen, Jan; Laursen, René J

2016-01-01

BACKGROUND: The Danish Neuro-Oncology Registry (DNOR) is a nationwide clinical cancer database that has prospectively registered data on patients with gliomas since January 2009. The purpose of this study was to describe the establishment of the DNOR and further to evaluate the database completen......BACKGROUND: The Danish Neuro-Oncology Registry (DNOR) is a nationwide clinical cancer database that has prospectively registered data on patients with gliomas since January 2009. The purpose of this study was to describe the establishment of the DNOR and further to evaluate the database...

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

Science.gov (United States)

Coder, Brandon; Wang, Weikan; Wang, Liefeng; Wu, Zhongdao; Zhuge, Qichuan; Su, Dong-Ming

2017-01-24

The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymus-inflammaging-neurodegeneration axis".

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

Science.gov (United States)

Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

Science.gov (United States)

Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

2016-12-01

In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Routine Data for Quality Assessment in NeuroNet Telestroke Care

DEFF Research Database (Denmark)

Theiss, Stephan; Günzel, Franziska; Storm, Anna

2013-01-01

: Routine clinical data from the HELIOS hospital information system were compared before and after implementation of the NeuroNet concept, including neurologic acute stroke teleconsultations, standard operating procedures, and peer review quality management in 3 hospital cohorts: 5 comprehensive stroke...... centers, 5 NeuroNet hospitals, and 5 matched control hospitals. RESULTS: During the study period, the rate of thrombolytic therapy increased by 4.8% in NeuroNet hospitals, while ischemic stroke in-hospital mortality decreased (relative risk reduction ∼29% in NeuroNet and control hospitals). The odds ratio...... for thrombolytic therapy in comprehensive stroke centers compared to NeuroNet hospitals was reduced from 3.7 to 1.3 between 2006 and 2009. Comprehensive stroke care coding according to German Diagnosis Related Groups definitions increased by 45% in NeuroNet (P

Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

Science.gov (United States)

Wolbring, Gregor; Diep, Lucy; Yumakulov, Sophya; Ball, Natalie; Leopatra, Verlyn; Yergens, Dean

2013-01-01

So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE). We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a) healthcare, healthcare policy, and healthcare ethics, (b) disability and (c) health consumers and how visible various assessment fields are within Neuro/Cogno/Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers) is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements. PMID:27429129

Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

Directory of Open Access Journals (Sweden)

Gregor Wolbring

2013-07-01

Full Text Available So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE. We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a healthcare, healthcare policy, and healthcare ethics, (b disability and (c health consumers and how visible various assessment fields are within Neuro/Cogno/ Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements.

Dynamics of Trace Element Concentration During Development and Excitotoxic Cell Death in the Cerebellum of Lurcher Mutant Mice

Czech Academy of Sciences Publication Activity Database

Bäurle, J.; Kučera, Jan; Frischmuth, S.; Lambertz, M.; Kranda, Karel

2009-01-01

Roč. 19, č. 4 (2009), s. 586-595 ISSN 1015-6305 R&D Projects: GA ČR GA309/09/1189 Institutional research plan: CEZ:AV0Z10480505 Keywords : apoptosis * copper * excitotoxicity Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 5.903, year: 2009

Mass Spectrometry Strategies for Clinical Metabolomics and Lipidomics in Psychiatry, Neurology, and Neuro-Oncology

Science.gov (United States)

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed. PMID:23842599

Mass spectrometry strategies for clinical metabolomics and lipidomics in psychiatry, neurology, and neuro-oncology.

Science.gov (United States)

Wood, Paul L

2014-01-01

Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed.

Phytochemical and therapeutic potential of cucumber.

Science.gov (United States)

Mukherjee, Pulok K; Nema, Neelesh K; Maity, Niladri; Sarkar, Birendra K

2013-01-01

Cucumber (Cucumis sativus L.) is a member of the Cucurbitaceae family like melon, squash and pumpkins. It is a popular vegetable crop used in Indian traditional medicine since ancient times. This vegetable is very high in water content and very low in calories. It has potential antidiabetic, lipid lowering and antioxidant activity. Cucumber has a cleansing action within the body by removing accumulated pockets of old waste materials and chemical toxins. Fresh fruit juice is used for nourishing the skin. It gives a soothing effect against skin irritations and reduces swelling. Cucumber also has the power to relax and alleviate the sunburn's pain. The fruit is refrigerant, haemostatic, tonic and useful in hyperdipsia, thermoplegia etc. The seeds also have a cooling effect on the body and they are used to prevent constipation. Several bioactive compounds have been isolated from cucumber including cucurbitacins, cucumegastigmanes I and II, cucumerin A and B, vitexin, orientin, isoscoparin 2″-O-(6‴-(E)-p-coumaroyl) glucoside, apigenin 7-O-(6″-O-p-coumaroylglucoside) etc. Despite huge exploration of cucumber in agricultural field, comparatively very few studies have been published about its chemical profile and its therapeutic potential. This article reviews the therapeutic application, pharmacological and phytochemical profile of different parts of C. sativus. In this review we have explored the current phytochemical and pharmacological knowledge available with this well known plant and several promising aspects for research on cucumber. Copyright © 2012 Elsevier B.V. All rights reserved.

NIH NeuroBioBank

Data.gov (United States)

Federal Laboratory Consortium — The NIH NeuroBioBank (NBB), supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy...

Ophthalmologic Findings in Patients with Neuro-metabolic Disorders.

Science.gov (United States)

Jafari, Narjes; Golnik, Karl; Shahriari, Mansoor; Karimzadeh, Parvaneh; Jabbehdari, Sayena

2018-01-01

We aimed to present the ophthalmic manifestations of neuro-metabolic disorders. Patients who were diagnosed with neuro-metabolic disorders in the Neurology Department of Mofid Pediatric Hospital in Tehran, Iran, between 2004 and 2014 were included in this study. Disorders were confirmed using clinical findings, neuroimaging, laboratory data, and genomic analyses. All enrolled patients were assessed for ophthalmological abnormalities. A total of 213 patients with 34 different neuro-metabolic disorders were included. Ophthalmological abnormalities were observed in 33.5% of patients. Abnormal findings in the anterior segment included Kayser-Fleischer rings, congenital or secondary cataracts, and lens dislocation into the anterior chamber. Posterior segment (i.e., retina, vitreous body, and optic nerve) evaluation revealed retinitis pigmentosa, cherry-red spots, and optic atrophy. In addition, strabismus, nystagmus, and lack of fixation were noted during external examination. Ophthalmological examination and assessment is essential in patients that may exhibit neuro-metabolic disorders.

Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, Friedreich's ataxia.

Science.gov (United States)

Chiang, Shannon; Kalinowski, Danuta S; Jansson, Patric J; Richardson, Des R; Huang, Michael L-H

2017-08-04

Mitochondrial homeostasis is essential for maintaining healthy cellular function and survival. The detrimental involvement of mitochondrial dysfunction in neuro-degenerative diseases has recently been highlighted in human conditions, such as Parkinson's, Alzheimer's and Huntington's disease. Friedreich's ataxia (FA) is another neuro-degenerative, but also cardio-degenerative condition, where mitochondrial dysfunction plays a crucial role in disease progression. Deficient expression of the mitochondrial protein, frataxin, is the primary cause of FA, which leads to adverse alterations in whole cell and mitochondrial iron metabolism. Dys-regulation of iron metabolism in these compartments, results in the accumulation of inorganic iron deposits in the mitochondrial matrix that is thought to potentiate oxidative damage observed in FA. Therefore, the maintenance of mitochondrial homeostasis is crucial in the progression of neuro-degenerative conditions, particularly in FA. In this review, vital mitochondrial homeostatic processes and their roles in FA pathogenesis will be discussed. These include mitochondrial iron processing, mitochondrial dynamics (fusion and fission processes), mitophagy, mitochondrial biogenesis, mitochondrial energy production and calcium metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

DEFF Research Database (Denmark)

Hwabejire, John O; Jin, Guang; Imam, Ayesha M

2013-01-01

Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether...

Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field

Directory of Open Access Journals (Sweden)

Lívia Brenelli de Paiva

2013-09-01

Full Text Available Ferulic acid is a phenolic acid widely distributed in the plant kingdom. It presents a wide range of potential therapeutic effects useful in the treatments of cancer, diabetes, lung and cardiovascular diseases, as well as hepatic, neuro and photoprotective effects and antimicrobial and anti-inflammatory activities. Overall, the pharmaceutical potential of ferulic acid can be attributed to its ability to scavenge free radicals. However, recent studies have revealed that ferulic acid presents pharmacological properties beyond those related to its antioxidant activity, such as the ability to competitively inhibit HMG-CoA reductase and activate glucokinase, contributing to reduce hypercholesterolemia and hyperglycemia, respectively. The present review addresses ferulic acid dietary sources, the pharmacokinetic profile, antioxidant action mechanisms and therapeutic effects in the treatment and prevention of various diseases, in order to provide a basis for understanding its mechanisms of action as well as its pharmaceutical potential.

NeuroD2 regulates the development of hippocampal mossy fiber synapses

Directory of Open Access Journals (Sweden)

Wilke Scott A

2012-02-01

Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

A comparative study of ANN and neuro-fuzzy for the prediction of ...

Indian Academy of Sciences (India)

Istanbul Technical University, Faculty of Civil Engineering, Hydraulics and Water. Resources Division, Maslak 34469, Istanbul, Turkey. Singh et al (2005) examined the potential of the ANN and neuro-fuzzy systems application for the prediction of dynamic constant of rockmass. However, the model proposed by them has ...

Quercetin: A wonder bioflvonoid with therapeutic potential in disease management

Directory of Open Access Journals (Sweden)

Alka Gupta

2016-03-01

Full Text Available In the last decade, considerable efforts have been made to develop health promising nutritional supplements. Quercetin is a plant-derived bioflavonoid which is recently gaining scientific interest for its antioxidant free radical scavenging effects and anti-inflammatory properties. This wonder flavanol exhibits therapeutic potential in various ailments like cancer, coronary artery, asthma and alzheimer (neurodegeneration diseases. Additional clinical uses include treatment of inflammatory conditions like gout, pancreatitis and prostatitis. It has been extensively studied for its gastroprotective effects, anti-obesity action, immune booster, reducing risk of cataract and reduction of diabetic complications. The present review briefly discusses about biological activity, mechanism of action and therapeutic potential of quercetin in prevention and mitigation of diseases.

Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

Science.gov (United States)

Simmons, Danielle A.

2017-01-01

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

Therapeutic potential of flurbiprofen against obesity in mice.

Science.gov (United States)

Hosoi, Toru; Baba, Sachiko; Ozawa, Koichiro

2014-06-20

Obesity is associated with several diseases including diabetes, nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease, and cancer. Therefore, anti-obesity drugs have the potential to prevent these diseases. In the present study, we demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited therapeutic potency against obesity. Mice were fed a high-fat diet (HFD) for 6 months, followed by a normal-chow diet (NCD). The flurbiprofen treatment simultaneously administered. Although body weight was significantly decreased in flurbiprofen-treated mice, growth was not affected. Flurbiprofen also reduced the HFD-induced accumulation of visceral fat. Leptin resistance, which is characterized by insensitivity to the anti-obesity hormone leptin, is known to be involved in the development of obesity. We found that one of the possible mechanisms underlying the anti-obesity effects of flurbiprofen may have been mediated through the attenuation of leptin resistance, because the high circulating levels of leptin in HFD-fed mice were decreased in flurbiprofen-treated mice. Therefore, flurbiprofen may exhibit therapeutic potential against obesity by reducing leptin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuro-oncology of CNS tumors

International Nuclear Information System (INIS)

Tonn, J.C.

2006-01-01

Diagnosis and treatment modalities for neuro-oncologic diseases have made considerable advances in recent years. There is hardly a segment of the field of solid tumours that is experiencing such dynamic development with regard to basic scientific findings and clinical results. In the present book the world's leading experts have compiled the current practice-relevant knowledge of neuro-oncologic diseases. The book's clear structure and the uniform presentation of all chapters make this volume a valuable reference, especially for practice-oriented activities, allowing swift access to information about current treatment standards. Hence it will be of great value to both clinicians and researchers. (orig.)

The Neuro-Complex: Some Comments and Convergences

Directory of Open Access Journals (Sweden)

Paul Martin

2011-10-01

Full Text Available In this short think-piece we trace the newly emerging and rapidly expanding dimensions and dynamics of the “neuro-complex.” What this amounts to, we suggest, are a series of bio or neuro “convergences” of sorts regarding the brain and mental worlds, which in turn are traceable through what we term the bio-psych, pharma-psych, subjectivity-selves, wellness-enhancement, and the neuroculture-neurofutures relational nexuses. These issues are then illustrated through two brief case studies regarding brain scanning technologies and the problems and prospects of cognitive enhancement. The paper concludes with some final reflections on these matters and a call for further research in this rich and challenging domain as the neuro-complex continues to expand in expected and unexpected, yet equally rich and fascinating, ways.

Determination of the therapeutic potential of human umbilical cord ...

African Journals Online (AJOL)

This research was conducted to evaluate the therapeutic potential of human umbilical cord blood, by determining their effect on bacterial pathogens which included: Streptobacillus sp, Corynebacterium diphtheriae, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. Cord blood samples were obtained ...

Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

Science.gov (United States)

Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

2016-12-01

Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

From 'Hard' Neuro-Tools to 'Soft' Neuro-Toys? Refocussing the Neuro-Enhancement Debate.

Science.gov (United States)

Brenninkmeijer, Jonna; Zwart, Hub

2017-01-01

Since the 1990's, the debate concerning the ethical, legal and societal aspects of 'neuro-enhancement' has evolved into a massive discourse, both in the public realm and in the academic arena. This ethical debate, however, tends to repeat the same sets of arguments over and over again. Normative disagreements between transhumanists and bioconservatives on invasive or radical brain stimulators, and uncertainties regarding the use and effectivity of nootropic pharmaceuticals dominate the field. Building on the results of an extensive European project on responsible research and innovation in neuro-enhancement (NERRI), we observe and encourage that the debate is now entering a new and, as we will argue, more realistic and societally relevant stage. This new stage concerns those technologies that enter the market as ostensibly harmless contrivances that consumers may use for self-care or entertainment. We use the examples and arguments of participants in NERRI debates to describe three case studies of such purportedly innocent 'toys'. Based upon this empirical material, we argue that these 'soft' enhancement gadgets are situated somewhere in the boundary zone between the internal and the external, between the intimate and the intrusive, between the familiar and the unfamiliar, between the friendly and the scary and, in Foucauldian terms, between technologies of the self and technologies of control. Therefore, we describe their physiognomy with the help of a term borrowed from Jacques Lacan, namely as "extimate" technologies.

Clinical PET/MR Imaging in Dementia and Neuro-Oncology

DEFF Research Database (Denmark)

Henriksen, Otto M.; Marner, Lisbeth; Law, Ian

2016-01-01

The introduction of hybrid PET/MRI systems allows simultaneous multimodality image acquisition of high technical quality. This technique is well suited for the brain, and particularly in dementia and neuro-oncology. In routine use combinations of well-established MRI sequences and PET tracers....../MRI using [18F]-fluoro-ethyl-tyrosine (FET) also abide to the expectations of the adaptive and versatile diagnostic tool necessary in neuro-oncology covering both simple 20 min protocols for routine treatment surveillance and complicated 90 min brain and spinal cord protocols in pediatric neuro...

Sequential gadolinium-DTPA enhanced MRI studies in neuro-Behcet's disease

International Nuclear Information System (INIS)

Kazui, S.; Naritomi, H.; Ogawa, M.; Sawada, T.; Imakita, S.; Yamada, N.

1991-01-01

Sequential gadolinium-DTPA (Gd-DTPA) enhanced MR images were obtained before and after steroid therapy in a case of neuro-Behcet's disease. Multiple scattered lesions, which could not be detected on pre- and post-contrast CT, were demonstrated mainly in the white matter of the pons and/or the cerebrum with both T1- and T2-weighted images. Some of these lesions, however, were not enhanced at all by infusion of Gd-DTPA. The Gd-DTPA infusion study demonstrated marked enhancement in the white matter of the pons and cerebrum. Some lesions not seen with T2-weighted images were also strongly enhanced by Gd-DTPA infusion at the acute stage. After steroid therapy, the symptoms and abnormal laboratory findings were resolved. The pontine and cerebral lesions on plain MR images remained unchanged even after resolution of the symptoms, suggesting that they were inactive old foci. On the other hand, the lesions detected in the enhancement study before steroid therapy disappeared with the repeat Gd-DTPA enhanced MR images which were performed after resolution of the symptoms. Some active inflammatory lesions in neuro-Behcet's disease may be demonstrated only on Gd-DTPA enhanced MR images. Gd-DTPA enhanced MR imaging appears to be potentially useful for detecting active inflammatory lesions in neuro-Behcet's disease and for evaluating the efficacy of treatment. (orig.)

Adaptive neuro-fuzzy controller of switched reluctance motor

Directory of Open Access Journals (Sweden)

Tahour Ahmed

2007-01-01

Full Text Available This paper presents an application of adaptive neuro-fuzzy (ANFIS control for switched reluctance motor (SRM speed. The ANFIS has the advantages of expert knowledge of the fuzzy inference system and the learning capability of neural networks. An adaptive neuro-fuzzy controller of the motor speed is then designed and simulated. Digital simulation results show that the designed ANFIS speed controller realizes a good dynamic behaviour of the motor, a perfect speed tracking with no overshoot and a good rejection of impact loads disturbance. The results of applying the adaptive neuro-fuzzy controller to a SRM give better performance and high robustness than those obtained by the application of a conventional controller (PI.

C-arm flat detector computed tomography: the technique and its applications in interventional neuro-radiology

International Nuclear Information System (INIS)

Kamran, Mudassar; Nagaraja, Sanjoy; Byrne, James V.

2010-01-01

Flat detector computed tomography (FDCT) is an imaging tool that generates three-dimensional (3-D) volumes from data obtained during C-arm rotation using CT-like reconstruction algorithms. The technique is relatively new and, at current levels of performance, lags behind conventional CT in terms of image quality. However, the advantage of its availability in the interventional room has prompted neuro-radiologists to identify clinical settings where its role is uniquely beneficial. We performed a search of the online literature databases to identify studies reporting experience with FDCT in interventional neuro-radiology. The studies were systematically reviewed and their findings grouped according to specific clinical situation addressed. FDCT images allow detection of procedural complications, evaluation of low-radiopacity stents and assessment of endosaccular coil packing in intra-cranial aneurysms. Additional roles are 3-D angiography that provides an accurate depiction of vessel morphology with low concentrations of radiographic contrast media and a potential for perfusion imaging due to its dynamic scanning capability. A single scan combining soft tissue and angiographic examinations reduces radiation dose and examination time. Ongoing developments in flat detector technology and reconstruction algorithms are expected to further enhance its performance and increase this range of applications. FDCT images provide useful information in neuro-interventional setting. If current research confirms its potential for assessing cerebral haemodynamics by perfusion scanning, the combination would redefine it as an invaluable tool for interventional neuro-radiology procedures. This facility and its existing capabilities of parenchymal and angiographic imaging would also extend its use to the triage of acute stroke patients. (orig.)

Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

International Nuclear Information System (INIS)

Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

2014-01-01

Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

Transgenic mice expressing a Huntington s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

OpenAIRE

Hansson, Oskar; Petersén, Åsa; Leist, Marcel; Nicotera, Pierluigi; Castilho, Roger F.; Brundin, Patrik

1999-01-01

Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant HD gene mediates a slowly progressing striatal neurotoxicity is unknown. Glutamate receptor-mediated excitotoxicity has been hypothesized to contribute to the pathogenesis of HD. Here we show that transgenic HD mice expressing exon 1 of a human HD gene with an expanded number of CAG repeats (line R...

Neuro-immune interactions via the cholinergic anti-inflammatory pathway

Science.gov (United States)

Gallowitsch-Puerta, Margot; Pavlov, Valentin A.

2010-01-01

The overproduction of TNF and other cytokines can cause the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed “the cholinergic anti-inflammatory pathway” that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent excessive inflammation. Experimental evidence indicates that vagus nerve cholinergic anti-inflammatory signaling requires alpha7 nicotinic acetylcholine receptors expressed on non-neuronal cytokine producing cells. Alpha7 nicotinic acetylcholine receptor agonists inhibit cytokine release and protect animals in a variety of experimental lethal inflammatory models. Knowledge related to the cholinergic anti-inflammatory pathway can be exploited in therapeutic approaches directed towards counteracting abnormal chronic and hyper-activated inflammatory responses. PMID:17289087

Regulatory roles and therapeutic potential of microRNA in sarcoma.

Science.gov (United States)

Lim, Hui Jun; Yang, Jia-Lin

2016-01-01

MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in various biological processes, including cell differentiation and development. They play multiple key roles as tumour suppressors, oncogenes or both in particular cases. This review aims to summarise current findings of the expression of miRNAs and their role in clinical oncology. Current knowledge regarding the involvement of miRNAs in different sarcoma subtypes will be assessed, in conjunction with their potential application as therapeutic targets. Relevant articles in scientific databases were identified using a combination of search terms, including "microRNA," "deregulation," "sarcoma," and "targeted therapy". These databases included Medline, Embase, Cochrane Review, Pubmed and Scopus. Aberrant miRNA expression patterns have been identified in a range of sarcoma subtypes, and differences in miRNA expression profiles between malignant cells and their normal counterparts suggests that miRNAs play key roles in sarcoma development. The identification of unique miRNA patterns in individual tumour types could possibly be used as a diagnostic tool in sarcoma. Moreover, identification of these miRNAs provides novel targets for the development of therapeutic strategies in distinct sarcoma subtypes. miRNAs hold significant potential as diagnostic biomarkers, as well as therapeutic targets in sarcoma. Possible future clinical applications include the use of miRNA pathways as therapeutic targets or miRNA expression profiling as a means of patient selection. The involvement miRNAs will undoubtedly contribute to the advancement of future targeted therapeutic interventions in sarcoma, and further establishment of appropriate delivery systems is vital for their use in clinical settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[NEURO-ONCOLOGY A NEW FIELD IN DAVIDOFF CANCER CENTER AT RABIN MEDICAL CENTER].

Science.gov (United States)

Yust-Katz, Shlomit; Limon, Dror; Abu-Shkara, Ramez; Siegal, Tali

2017-08-01

Neuro-oncology is a subspecialty attracting physicians from medical disciplines such as neurology, neurosurgery, pediatrics, oncology, and radiotherapy. It deals with diagnosis and management of primary brain tumors, as well as metastatic and non-metastatic neurological manifestations that frequently affect cancer patients including brain metastases, paraneoplastic syndromes and neurological complications of cancer treatment. A neuro-oncology unit was established in Davidoff Cancer Center at Rabin Medical Center. It provides a multidisciplinary team approach for management of brain tumors and services, such as expert outpatient clinics and inpatient consultations for the departments of oncology, hematology, bone marrow transplantation and other departments in the Rabin Medical Center. In addition, expert consultation is frequently provided to other hospitals that treat cancer patients with neurological manifestations. The medical disciplines that closely collaborate for the daily management of neuro-oncology patients include radiotherapy, hematology, oncology, neuro-surgery, neuro-radiology and neuro-pathology. The neuro-oncology center is also involved in clinical and laboratory research conducted in collaboration with researchers in Israel and abroad. The new service contributes substantially to the improved care of cancer patients and to the advance of research topics in the field of neuro-oncology.

Neuroæstetik eller kunst på hjernen

DEFF Research Database (Denmark)

Clasen, Mathias

2009-01-01

Neuroæstetikken kombinerer hjerneforskning, æstetikforskning og eksperimentel psykologi -- alt sammen for at forstå en af Homo sapiens' mest bizarre hobbyer: kunst. Forskning i kunstens neurobiologi griber om sig.......Neuroæstetikken kombinerer hjerneforskning, æstetikforskning og eksperimentel psykologi -- alt sammen for at forstå en af Homo sapiens' mest bizarre hobbyer: kunst. Forskning i kunstens neurobiologi griber om sig....

[Neuro-rehabilitation after stroke].

Science.gov (United States)

Murie-Fernández, M; Irimia, P; Martínez-Vila, E; John Meyer, M; Teasell, R

2010-04-01

the high incidence of stroke results in significant mortality and disability leading to immense health care costs. These costs lead to socioeconomic, budgetary, and staffing repercussions in developing countries. Improvements in stroke management focus mainly on acute neurological treatment, admission to stroke units, fibrinolytic treatment for ischaemic strokes and rehabilitation processes. Among these, rehabilitation has the longest therapeutic window, can be applied in both ischaemic and haemorrhagic strokes, and can improve functional outcomes months after stroke. Neurologists, because of their knowledge in neuroanatomy, physiopathology, neuro-pharmacology, and brain plasticity, are in an ideal position to actively participate in the neurorehabilitation process. Several processes have been shown to play a role in determining the efficacy of rehabilitation; time from stroke onset to rehabilitation admission and the duration and intensity of treatment. neurorehabilitation is a sub-speciality in which neurologists should be incorporated into multidisciplinary neurorehabilitation teams. Early time to rehabilitation admission and greater intensity and duration of treatment are associated with better functional outcomes, lower mortality/institutionalisation, and shorter length of stay. In order to be efficient, a concerted effort must be made to ensure patients receive neurorehabilitation treatment in a timely manner with appropriate intensity to maximize patient outcomes during both inpatient and outpatient rehabilitation. Published by Elservier España, S.L. All rights reserved.

ON POLISH FANTASTIC LITERATURE FOR YOUNG PEOPLE AND ITS THERAPEUTIC POTENTIAL

Directory of Open Access Journals (Sweden)

Dominik Borowski

2017-04-01

Full Text Available The objective of this article is to provide an overview of the therapeutic potential of fantastic literature for young people on the example of the series of novels by Rafał Kosik. The paper consists of three parts. The first part presents the definition of fantastic literature with reference to the concepts introduced by Tzvetan Todorov, Roger Caillois, Eric Rabkin and dictionary entries. Then the therapeutic function of literature is discussed by citing psychological theses on the importance of narrative in human life, as well as Roman Ingarden’s theory of the aesthetic experience. This provides the basis for reflection on bibliotherapy and the use of fantastic literature within its framework. The third part of the article presents the concept of the series of novels about Felix, Net and Nika, referring to the opinions of critics and literary scholars. Subsequently the selected fragments of the novels are discussed, demonstrating their therapeutic potential.

Roles of neuro-exocytotic proteins at the neuromuscular junction

NARCIS (Netherlands)

Sons-Michel, Michèle S.

2011-01-01

The aim of the studies described in the thesis was to elucidate the roles of several neuro-exocytotic proteins at the motor nerve terminal in neuromuscular synaptic transmission, making use of genetic knockout (KO) mice, each missing one (or more) neuro-exocytotic proteins. In addition, it was

Pediatric neuro MRI. Tricks to minimize sedation

Energy Technology Data Exchange (ETDEWEB)

Barkovich, Matthew J.; Desikan, Rahul S. [University of California, San Francisco, Department of Radiology and Diagnostic Imaging, San Francisco, CA (United States); Xu, Duan; Barkovich, A.J. [University of California, San Francisco, Department of Radiology and Diagnostic Imaging, San Francisco, CA (United States); UCSF-Benioff Children' s Hospital, Department of Radiology, San Francisco, CA (United States); Williams, Cassandra [UCSF-Benioff Children' s Hospital, Department of Radiology, San Francisco, CA (United States)

2018-01-15

Magnetic resonance imaging (MRI) is the workhorse modality in pediatric neuroimaging because it provides excellent soft-tissue contrast without ionizing radiation. Until recently, studies were uninterpretable without sedation; however, given development of shorter sequences, sequences that correct for motion, and studies showing the potentially deleterious effects of sedation on immature laboratory animals, it is prudent to minimize sedation when possible. This manuscript provides basic guidelines for performing pediatric neuro MRI without sedation by both modifying technical factors to reduce scan time and noise, and using a multi-disciplinary team to coordinate imaging with the patient's biorhythms. (orig.)

Neuro-rejuvenation for neuronal function

Institute of Scientific and Technical Information of China (English)

Yuan Liu; Richard K. Lee

2016-01-01

Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell (RGC) death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu-rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.

Neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn. leaf in male Wistar rat model of cyclophosphamide-induced reproductive toxicity

Directory of Open Access Journals (Sweden)

Oladele Abiodun Ayoka

Full Text Available Cyclophosphamide (CP is a widely used cytotoxic alkylating agent with antitumor and immunosuppressant properties that is associated with various forms of reproductive toxicity. The significance of natural antioxidants of plant origin should be explored, especially in a world with increasing incidence of patients in need of chemotherapy. The neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn. leaf (AEAVL in Wistar rats with CP-induced reproductive toxicity was determined. Forty rats were used for this study such that graded doses of the extract were administered following CP-induced reproductive toxicity and comparisons were made against control, toxic and standard (vitamin E groups at p < 0.05. The synthetic drugs (CP, 65 mg/kg i.p. for 5 days; Vitamin E, 100 mg/kg p.o. for 30 days as well as the extract (100, 200 and 400 mg/kg p.o. for 30 days were administered to the rats at 0.2 mL/100 g. CP induced reproductive toxicity as evidenced by significantly lowered levels of FSH, LH and testosterone, perturbation of sperm characterization, deleterious disruptions of the antioxidant system as evidenced by decreased levels of GSH as well as elevation of TBARS activity. Histopathological examination showed hemorrhagic lesions with scanty and hypertrophied parenchymal cells in the pituitary while the testis showed ballooned seminiferous tubules with loosed connective tissues and vacuolation of testicular interstitium. These conditions were significantly reversed (p < 0.05 following administration of the graded doses of the extract. It was, therefore, concluded that AEAVL could potentially be a therapeutic choice in patients with CP-induced neuro-endocrine dysfunction and reproductive toxicity. Keywords: Cyclophosphamide, Neuro-endocrine dysfunction, Reproductive toxicity, Rats, Amaranthus viridis

Analysis and prediction of flow from local source in a river basin using a Neuro-fuzzy modeling tool.

Science.gov (United States)

Aqil, Muhammad; Kita, Ichiro; Yano, Akira; Nishiyama, Soichi

2007-10-01

Traditionally, the multiple linear regression technique has been one of the most widely used models in simulating hydrological time series. However, when the nonlinear phenomenon is significant, the multiple linear will fail to develop an appropriate predictive model. Recently, neuro-fuzzy systems have gained much popularity for calibrating the nonlinear relationships. This study evaluated the potential of a neuro-fuzzy system as an alternative to the traditional statistical regression technique for the purpose of predicting flow from a local source in a river basin. The effectiveness of the proposed identification technique was demonstrated through a simulation study of the river flow time series of the Citarum River in Indonesia. Furthermore, in order to provide the uncertainty associated with the estimation of river flow, a Monte Carlo simulation was performed. As a comparison, a multiple linear regression analysis that was being used by the Citarum River Authority was also examined using various statistical indices. The simulation results using 95% confidence intervals indicated that the neuro-fuzzy model consistently underestimated the magnitude of high flow while the low and medium flow magnitudes were estimated closer to the observed data. The comparison of the prediction accuracy of the neuro-fuzzy and linear regression methods indicated that the neuro-fuzzy approach was more accurate in predicting river flow dynamics. The neuro-fuzzy model was able to improve the root mean square error (RMSE) and mean absolute percentage error (MAPE) values of the multiple linear regression forecasts by about 13.52% and 10.73%, respectively. Considering its simplicity and efficiency, the neuro-fuzzy model is recommended as an alternative tool for modeling of flow dynamics in the study area.

Authenticity anyone? : the enhancement of emotions via neuro-psychopharmacology

NARCIS (Netherlands)

Kraemer, U.A.F.

2011-01-01

This article will examine how the notion of emotional authenticity is intertwined with the notions of naturalness and artificiality in the context of the recent debates about ‘neuro-enhancement’ and ‘neuro-psychopharmacology.’ In the philosophy of mind, the concept of authenticity plays a key role

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

Science.gov (United States)

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

Science.gov (United States)

Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

2013-04-01

Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

Potential of neuro-fuzzy methodology to estimate noise level of wind turbines

Science.gov (United States)

Nikolić, Vlastimir; Petković, Dalibor; Por, Lip Yee; Shamshirband, Shahaboddin; Zamani, Mazdak; Ćojbašić, Žarko; Motamedi, Shervin

2016-01-01

Wind turbines noise effect became large problem because of increasing of wind farms numbers since renewable energy becomes the most influential energy sources. However, wind turbine noise generation and propagation is not understandable in all aspects. Mechanical noise of wind turbines can be ignored since aerodynamic noise of wind turbine blades is the main source of the noise generation. Numerical simulations of the noise effects of the wind turbine can be very challenging task. Therefore in this article soft computing method is used to evaluate noise level of wind turbines. The main goal of the study is to estimate wind turbine noise in regard of wind speed at different heights and for different sound frequency. Adaptive neuro-fuzzy inference system (ANFIS) is used to estimate the wind turbine noise levels.

Sensitivity Verification of PWR Monitoring System Using Neuro-Expert For LOCA Detection

International Nuclear Information System (INIS)

Muhammad Subekti

2009-01-01

Sensitivity Verification of PWR Monitoring System Using Neuro-Expert For LOCA Detection. The present research was done for verification of previous developed method on Loss of Coolant Accident (LOCA) detection and perform simulations for knowing the sensitivity of the PWR monitoring system that applied neuro-expert method. The previous research continuing on present research, has developed and has tested the neuro-expert method for several anomaly detections in Nuclear Power Plant (NPP) typed Pressurized Water Reactor (PWR). Neuro-expert can detect the LOCA anomaly with sensitivity of primary coolant leakage of 7 gallon/min and the conventional method could not detect the primary coolant leakage of 30 gallon/min. Neuro expert method detects significantly LOCA anomaly faster than conventional system in Surry-1 NPP as well so that the impact risk is reducible. (author)

Improving neuro-oncological patients care: basic and practical concepts for nurse specialist in neuro-rehabilitation

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Bartolo Michelangelo

2012-10-01

Full Text Available Abstract Background Neuro-oncological population well expresses the complexity of neurological disability due to the multiple neurological deficits that affect these patients. Moreover, due to the therapeutical opportunities survival times for patients with brain tumor have increased and more of these patients require rehabilitation care. The figure of nurse in the interdisciplinary specialty of neurorehabilitation is not clearly defined, even if their role in this setting is recognized as being critical and is expanding. The purpose of the study is to identify the standard competencies for neurorehabilitation nurses that could be taught by means of a specialization course. Methods A literature review was conducted with preference given to works published between January 2000 and December 2008 in English. The search strategy identified 523 non-duplicated references of which 271 titles were considered relevant. After reviewing the abstracts, 147 papers were selected and made available to a group of healthcare professionals who were requested to classify them in few conceptual main areas defining the relative topics. Results The following five main areas were identified: clinical aspects of nursing; nursing techniques; nursing methodology; relational and organisational models; legal aspects of nursing. The relative topics were included within each area. As educational method a structured course based on lectures and practical sessions was designed. Also multi-choices questions were developed in order to evaluate the participants’ level of knowledge, while a semi-structured interview was prepared to investigate students’ satisfaction. Conclusions Literature shows that the development of rehabilitation depends on the improvement of scientific and practical knowledge of health care professionals. This structured training course could be incorporated into undergraduate nursing education programmes and also be inserted into continuing education

Contextualizing Neuro-Collaborations: Reflections on a Transdisciplinary fMRI Lie Detection Experiment

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Melissa M. Littlefield

2014-03-01

Full Text Available Recent neuroscience initiatives (including the E.U.’s Human Brain Project and the U.S.’s BRAIN Initiative have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers’ own experiences of working between disciplines – a phenomenon that we call ‘Disciplinary Double Consciousness’ (DDC. Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature, we argue that ‘neuro-collaborations’ inevitably engage researchers in DDC – a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a home discipline and a secondary discipline. Our case study is a five-year case study in fMRI lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations.

AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated and dependent upon receptor desensitization

DEFF Research Database (Denmark)

Jensen, J B; Schousboe, A; Pickering, D S

1998-01-01

with a fast and rapidly desensitizing response, this could explain the relatively low toxicity produced by 500 microM AMPA. This was investigated by blocking AMPA receptor desensitization with cyclothiazide. Using a lower concentration (25 microM) of AMPA, addition of 50 microM cyclothiazide increased...... the AMPA induced excitotoxicity in cultured cortical neurons at all DIV except for DIV 2. This combination of AMPA + cyclothiazide yielded 77% cell death for DIV 12 cultures. In contrast to the results observed with 500 microM AMPA, the neurotoxicity mediated directly by AMPA receptors when desensitization...

Palliative Care Needs Assessment in the Neuro-ICU: Effect on Family.

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Creutzfeldt, Claire J; Hanna, Marina G; Cheever, C Sherry; Lele, Abhijit V; Spiekerman, Charles; Engelberg, Ruth A; Curtis, J Randall

2017-10-01

Examine the association of a daily palliative care needs checklist on outcomes for family members of patients discharged from the neurosciences intensive care unit (neuro-ICU). We conducted a prospective, longitudinal cohort study in a single, thirty-bed neuro-ICU in a regional comprehensive stroke and level 1 trauma center. One of two neuro-ICU services that admit patients to the same ICU on alternating days used a palliative care needs checklist during morning work rounds. Between March and October, 2015, surveys were mailed to family members of patients discharged from the neuro-ICU. Nearly half of surveys (n = 91, 48.1%) were returned at a median of 4.7 months. At the time of survey completion, mean Modified rankin scale score (mRS) of neuro-ICU patients was 3.1 (SD 2). Overall ratings of quality of care were relatively high (82.2 on a 0-100 scale) with 32% of family members meeting screening criteria for depressive syndrome. The primary outcome measuring family satisfaction, consisting of eight items from the Family Satisfaction in the ICU questionnaire, did not differ significantly between families of patients from either ICU service nor did family ratings of depression (PHQ-8) and post-traumatic stress (PCL-17). Among families of patients discharged from the neuro-ICU, the daily use of a palliative care needs checklist had no measurable effect on family satisfaction scores or long-term psychological outcomes. Further research is needed to identify optimal interventions to meet the palliative care needs specific to family members of patients treated in the neuro-ICU.

Statistically qualified neuro-analytic failure detection method and system

Science.gov (United States)

Vilim, Richard B.; Garcia, Humberto E.; Chen, Frederick W.

2002-03-02

An apparatus and method for monitoring a process involve development and application of a statistically qualified neuro-analytic (SQNA) model to accurately and reliably identify process change. The development of the SQNA model is accomplished in two stages: deterministic model adaption and stochastic model modification of the deterministic model adaptation. Deterministic model adaption involves formulating an analytic model of the process representing known process characteristics, augmenting the analytic model with a neural network that captures unknown process characteristics, and training the resulting neuro-analytic model by adjusting the neural network weights according to a unique scaled equation error minimization technique. Stochastic model modification involves qualifying any remaining uncertainty in the trained neuro-analytic model by formulating a likelihood function, given an error propagation equation, for computing the probability that the neuro-analytic model generates measured process output. Preferably, the developed SQNA model is validated using known sequential probability ratio tests and applied to the process as an on-line monitoring system. Illustrative of the method and apparatus, the method is applied to a peristaltic pump system.

Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

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Mora Paolo

2013-01-01

Full Text Available Abstract Neuro-Behçet’s disease (NBD involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension; thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet’s disease (BD; the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1. We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases. In 19/53 patients (36%, neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine. Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our

Release of neuropeptides from a neuro-cutaneous co-culture model: A novel in vitro model for studying sensory effects of ciguatoxins.

Science.gov (United States)

Le Garrec, Raphaele; L'herondelle, Killian; Le Gall-Ianotto, Christelle; Lebonvallet, Nicolas; Leschiera, Raphael; Buhe, Virginie; Talagas, Matthieu; Vetter, Irina; Lewis, Richard J; Misery, Laurent

2016-06-15

Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuro-models for discharge air temperature system

International Nuclear Information System (INIS)

Zaheer-uddin, M.; Tudoroiu, N.

2004-01-01

Nonlinear neuro-models for a discharge air temperature (DAT) system are developed. Experimental data gathered in a heating ventilating and air conditioning (HVAC) test facility is used to develop multi-input multi-output (MIMO) and single-input single-output (SISO) neuro-models. Several different network architectures were explored to build the models. Results show that a three layer second order neural network structure is necessary to achieve good accuracy of the predictions. Results from the developed models are compared, and some observations on sensitivity and standard deviation errors are presented

Neuro-fuzzy modelling of hydro unit efficiency

International Nuclear Information System (INIS)

Iliev, Atanas; Fushtikj, Vangel

2003-01-01

This paper presents neuro-fuzzy method for modeling of the hydro unit efficiency. The proposed method uses the characteristics of the fuzzy systems as universal function approximates, as well the abilities of the neural networks to adopt the parameters of the membership's functions and rules in the consequent part of the developed fuzzy system. Developed method is practically applied for modeling of the efficiency of unit which will be installed in the hydro power plant Kozjak. Comparison of the performance of the derived neuro-fuzzy method with several classical polynomials models is also performed. (Author)

Therapeutic potential of abalone and status of bioactive molecules: A comprehensive review.

Science.gov (United States)

Suleria, H A R; Masci, P P; Gobe, G C; Osborne, S A

2017-05-24

Marine organisms are increasingly being investigated as sources of bioactive molecules with therapeutic applications as nutraceuticals and pharmaceuticals. In particular, nutraceuticals are gaining popularity worldwide owing to their therapeutic potential and incorporation in functional foods and dietary supplements. Abalone, a marine gastropod, contains a variety of bioactive compounds with anti-oxidant, anti-thrombotic, anti-inflammatory, anti-microbial, and anti-cancer activities. For thousands of years different cultures have used abalone as a traditional functional food believing consumption provides health benefits. Abalone meat is one of the most precious commodities in Asian markets where it is considered a culinary delicacy. Recent research has revealed that abalone is composed of many vital moieties like polysaccharides, proteins, and fatty acids that provide health benefits beyond basic nutrition. A review of past and present research is presented with relevance to the therapeutic potential of bioactive molecules from abalone.

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

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Chui-Mian Zeng

2018-05-01

Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Bernardino, Liliana; Xapelli, Sara; Silva, Ana P

2005-01-01

The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects...... of mouse recombinant TNF-alpha (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-alpha to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol....... By using TNF-alpha receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-alpha involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed...

Neuro-ophthalmic and clinical characteristics of brain tumours in a ...

African Journals Online (AJOL)

Background: Anecdotally, increasing number of patients are seen at Korle Bu Teaching Hospital (KBTH) with brain tumour. Neuro-ophthalmic symptoms and signs may help in timely diagnosis and intervention. Objective: To evaluate the neuro-ophthalmic and clinical characteristics of brain tumour in patients presenting at a ...

Cascade control of superheated steam temperature with neuro-PID controller.

Science.gov (United States)

Zhang, Jianhua; Zhang, Fenfang; Ren, Mifeng; Hou, Guolian; Fang, Fang

2012-11-01

In this paper, an improved cascade control methodology for superheated processes is developed, in which the primary PID controller is implemented by neural networks trained by minimizing error entropy criterion. The entropy of the tracking error can be estimated recursively by utilizing receding horizon window technique. The measurable disturbances in superheated processes are input to the neuro-PID controller besides the sequences of tracking error in outer loop control system, hence, feedback control is combined with feedforward control in the proposed neuro-PID controller. The convergent condition of the neural networks is analyzed. The implementation procedures of the proposed cascade control approach are summarized. Compared with the neuro-PID controller using minimizing squared error criterion, the proposed neuro-PID controller using minimizing error entropy criterion may decrease fluctuations of the superheated steam temperature. A simulation example shows the advantages of the proposed method. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

A neuro-fuzzy model for prediction of the indoor temperature in typical Australian residential buildings

Energy Technology Data Exchange (ETDEWEB)

Alasha' ary, Haitham; Moghtaderi, Behdad; Page, Adrian; Sugo, Heber [Priority Research Centre for Energy, Chemical Engineering, School of Engineering, Faculty of Engineering and Built Environment, the University of Newcastle, Callaghan, Newcastle, NSW 2308 (Australia)

2009-07-15

The Masonry Research Group at The University of Newcastle, Australia has embarked on an extensive research program to study the thermal performance of common walling systems in Australian residential buildings by studying the thermal behaviour of four representative purpose-built thermal test buildings (referred to as 'test modules' or simply 'modules' hereafter). The modules are situated on the university campus and are constructed from brick veneer (BV), cavity brick (CB) and lightweight (LW) constructions. The program of study has both experimental and analytical strands, including the use of a neuro-fuzzy approach to predict the thermal behaviour. The latter approach employs an experimental adaptive neuro-fuzzy inference system (ANFIS) which is used in this study to predict the room (indoor) temperatures of the modules under a range of climatic conditions pertinent to Newcastle (NSW, Australia). The study shows that this neuro-fuzzy model is capable of accurately predicting the room temperature of such buildings; thus providing a potential computationally efficient and inexpensive predictive tool for the more effective thermal design of housing. (author)

Dendrimers as Potential Therapeutic Tools in HIV Inhibition

Directory of Open Access Journals (Sweden)

Xiangbo Li

2013-07-01

Full Text Available The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection.

Bee venom therapy: Potential mechanisms and therapeutic applications.

Science.gov (United States)

Zhang, Shuai; Liu, Yi; Ye, Yang; Wang, Xue-Rui; Lin, Li-Ting; Xiao, Ling-Yong; Zhou, Ping; Shi, Guang-Xia; Liu, Cun-Zhi

2018-04-11

Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

Science.gov (United States)

Segal, Scott; Narayanan, Ramesh; Dalton, James T

2006-04-01

Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

[Whiplash injury as a function of the accident mechanism. Neuro-otological differential diagnostic findings].

Science.gov (United States)

Geiger, G; Aliyev, R M

2012-07-01

Depending on the type of collision, car occupants who are involved in traffic accidents are often exposed to the unexpected effects on the cervical spine of traumatic stimuli from different directions. In a rear-end collision or a frontal collision of the car it is most likely that there is an effect of linear acceleration and a lateral or side impact acceleration of axial rotation on the cervical spine. The neuro-otological manifestations of whiplash injuries that can occur in response to various trauma mechanisms have not yet been sufficiently investigated. Data from 64 patients who suffered a whiplash injury were selected for analysis. In 32 patients the trauma mechanism was a sudden action on the cervical spine from a linear impulse caused by a head-on collision of cars or rear-end collision. In the other 32 patients the trauma mechanism was a sudden action of an axial neck rotation at a side impact collision or a cross collision. The study compared the results of neuro-otological findings between the two patient groups. A comparison of the neuro-otological examination data of 64 patients revealed that there were 32 patients who had a sudden injury mechanism of cervical axial rotation, the prevalence of central vestibular and sensory impairments, such as pathological central nystagmus disinhibition, pathological changes in the auditory brainstem evoked potentials (ABEP), the auditory evoked cortical potentials (ALEP) and visual evoked potentials (VEP). In the second group of patients where the injury mechanism consisted of an unexpected linear momentum, peripheral vestibular and sensory disorders were predominant. The observed differences in neuro-otological manifestations of whiplash trauma, which occur depending on the trauma mechanism, can be used for differential diagnostic purposes. The whiplash injuries of the cervical spine induced by an axial rotation acceleration showed a prevalence of central vestibular and sensory disturbances, while the whiplash

Neuro-Ophthalmology at a Tertiary Eye Care Centre in India.

Science.gov (United States)

Dhiman, Rebika; Singh, Digvijay; Gantayala, Shiva P; Ganesan, Vaitheeswaran L; Sharma, Pradeep; Saxena, Rohit

2017-11-09

Neuro-ophthalmology as a specialty is underdeveloped in India. The aim of our study was to determine the spectrum and profile of patients presenting to a tertiary eye care center with neuro-ophthalmic disorders. A retrospective hospital-based study was conducted, and records of all patients seen at the neuro-ophthalmology clinic of Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India, over a 1-year period were retrieved and evaluated. Of a total of 30,111 patients referred to various specialty clinics in a span of 1 year, 1597 (5%) were referred for neuro-ophthalmology evaluation. The mean patient age was 30.8 ± 19.5 years, with a male dominance (M:F = 2.02:1). Among these patients, optic nerve disorders were noted in 63.8% (n = 1,020), cranial nerve palsy in 7% (n = 114), cortical visual impairment in 6.5% (n = 105), and others (eye/optic nerve hypophasia, blepharospasm, and optic disc drusen) in 6% (n = 95). Among the patients with optic nerve disorders, optic neuropathy without disc edema/(traumatic optic neuropathy, hereditary, tumor-related, retrobulbar neuritis, toxic, and idiopathic) was noted in 42.8% (n = 685) and optic neuropathy with disc edema (ischemic optic neuropathy, papilledema, post-papilledema optic atrophy, papillitis, neuroretinitis, and inflammatory optic neuropathy) in 20.9% (n = 335). Sixteen percent of patients (n = 263) were incorrect referrals. The neuro-ophthalmic clinic constitutes a significant referral unit in a tertiary eye care center in India. Traumatic and ischemic optic neuropathies are the most common diagnoses. Neuro-ophthalmology requires further development as a subspecialty in India to better serve the nation's population.

Urocortin 2 treatment is protective in excitotoxic retinal degeneration.

Science.gov (United States)

Szabadfi, K; Kiss, P; Reglodi, D; Fekete, E M; Tamas, A; Danyadi, B; Atlasz, T; Gabriel, R

2014-03-01

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

Science.gov (United States)

Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

2016-10-01

Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.

Science.gov (United States)

Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu

2017-03-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Gut microbiota drive the development of neuro-inflammatory response in cirrhosis

Science.gov (United States)

Kang, Dae Joong; Betrapally, Naga S; Ghosh, Siddhartha A; Sartor, R Balfour; Hylemon, Phillip B; Gillevet, Patrick M; Sanyal, Arun J; Heuman, Douglas M; Carl, Daniel; Zhou, Huiping; Liu, Runping; Wang, Xiang; Yang, Jing; Jiao, Chunhua; Herzog, Jeremy; Lippmann, H Robert; Sikaroodi, Masoumeh; Brown, Robert R; Bajaj, Jasmohan S

2016-01-01

The mechanisms behind the development of hepatic encephalopathy (HE) are unclear although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. Aim Define the individual contribution of hyperammonemia and systemic inflammation on neuro-inflammation in cirrhosis using germ-free (GF) and conventional mice. Methods GF and conventional C57BL/6 mice were made cirrhotic using CCl4 gavage. These were compared to their non-cirrhotic counterparts. Intestinal microbiota, systemic and neuro-inflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity and cecal glutamine content were compared between groups. Results GF-cirrhotic mice developed similar cirrhotic changes to the conventional mice after four extra weeks (16 vs. 12 weeks) of CCL4 gavage. GF-cirrhotic mice exhibited higher ammonia compared to the GF controls but this was not associated with systemic or neuro-inflammation. Ammonia was generated through increased small intestinal glutaminase activity with concomitantly reduced intestinal glutamine levels. However, conventional cirrhotic mice had intestinal dysbiosis as well as systemic inflammation, associated with increased serum ammonia compared to conventional controls. This was associated with neuro-inflammation and glial/microglial activation. Correlation network analysis in conventional mice showed significant linkages between systemic/neuro-inflammation, intestinal microbiota and ammonia. Specifically beneficial, autochthonous taxa were negatively linked with brain and systemic inflammation, ammonia and with Staphylococcaceae, Lactobacillaceae and Streptococcaceae. Enterobacteriaceae were positively linked with serum inflammatory cytokines Conclusions Gut microbiota changes drive the development of neuro- and systemic inflammatory responses in cirrhotic animals. PMID:27339732

Neuro-QoL health-related quality of life measurement system: Validation in Parkinson's disease.

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Nowinski, Cindy J; Siderowf, Andrew; Simuni, Tanya; Wortman, Catherine; Moy, Claudia; Cella, David

2016-05-01

Neuro-QoL is a multidimensional patient-reported outcome measurement system assessing aspects of physical, mental, and social health identified by neurology patients and caregivers as important. One of the first neurology-specific patient-reported outcome measure systems created using modern test development methods, Neuro-Qol enables brief, yet precise, assessment and the ability to conduct both PD-specific and cross-disease comparisons. We present results of Neuro-QoL clinical validation using a sample of PD patients. A total of 120 PD patients recruited from academic medical centers were assessed at baseline, 1 week, and 6 months. Assessments included Neuro-QoL and general and PD-specific validity measures. Participants were 62% male and 95% white (average age = 66); H & Y stages were 1 (16%), 2 (61%), 3 (18%), and 4 (5%). Internal consistency and test-retest reliability of Neuro-QoL ranged from Cronbach's alphas = 0.81 to 0.94 with intraclass correlation coefficients = 0.66 to 0.80. Pearson's correlations between Neuro-QoL and legacy measures were generally moderate and in expected directions. UPDRS Part 2 was moderately correlated with Neuro-QoL Upper Extremity and Mobility, respectively (r's = -0.44; -0.59). Parkinson's Disease Questionnaire-39 and Neuro-QoL measures of similar constructs showed strong-to-moderate correlations (r's = 0.70-0.44). Neuro-QoL measures of fatigue, mobility, positive emotion, and emotional/behavioral control showed responsiveness to self-reported change. Neuro-QoL is valid for use in PD clinical research. Reliability for all but two measures is sufficient for group comparisons, with some evidence supporting responsiveness to change. Neuro-QoL possesses characteristics, such as brevity, flexibility in administration, and suitability, for cross-disease comparisons that may be advantageous to users in a variety of settings. © 2016 Movement Disorder Society. © 2016 International Parkinson and Movement Disorder

Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.

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Rehana Parvin

Full Text Available The mechanism of the negative regulation of proopiomelanocortin gene (Pomc by glucocorticoids (Gcs is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1 in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX (1-100 nM and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58 activity was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter activity were inhibited by DEX in a dose-dependent manner. Deletion and point mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional repression was mediated via E-box that exists at -376/-371 in the promoter. Since NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose-dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb activity, and NeuroD1 protein expression in AtT20 cells. In addition, we confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on Pomc promoter by chromatin immunoprecipitation (ChIP assay. Finally, overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc mRNA expression and Pomc promoter activity. Taken together, it is suggested that the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box interaction may play an important role in the Gc-mediated negative regulation of Pomc.

A Portable Ultrasound System for Non-Invasive Ultrasonic Neuro-Stimulation.

Science.gov (United States)

Qiu, Weibao; Zhou, Juan; Chen, Yan; Su, Min; Li, Guofeng; Zhao, Huixia; Gu, Xianyi; Meng, De; Wang, Congzhi; Xiao, Yang; Lam, Kwok Ho; Dai, Jiyan; Zheng, Hairong

2017-12-01

Fundamental insights into the function of the neural circuits often follows from the advances in methodologies and tools for neuroscience. Electrode- and optical- based stimulation methods have been used widely for neuro-modulation with high resolution. However, they are suffering from inherent invasive surgical procedure. Ultrasound has been proved as a promising technology for neuro-stimulation in a non-invasive manner. However, no portable ultrasound system has been developed particularly for neuro-stimulation. The utilities used currently are assembled by traditional functional generator, power amplifier, and general transducer, therefore, resulting in lack of flexibility. This paper presents a portable system to achieve ultrasonic neuro-stimulation to satisfy various studies. The system incorporated a high voltage waveform generator and a matching circuit that were optimized for neuro-stimulation. A new switching mode power amplifier was designed and fabricated. The noise generated by the power amplifier was reduced (about 30 dB), and the size and weight were smaller in contrast with commercial equipment. In addition, a miniaturized ultrasound transducer was fabricated using Pb(Mg 1/3 Nb 2/3 )O 3 -PbTiO 3 (PMN-PT) 1-3 composite single crystal for the improved ultrasonic performance. The spatial peak temporal average pressure was higher than 250 kPa in the range of 0.5-5 MHz. In vitro and in vivo studies were conducted to show the performance of the system.

OpenCL Implementation of NeuroIsing

Science.gov (United States)

Zapart, C. A.

Recent advances in graphics card hardware combined with anintroduction of the OpenCL standard promise to accelerate numerical simulations across diverse scientific disciplines. One such field benefiting from new hardware/software paradigms is econophysics. The paper describes an OpenCL implementation of a selected econophysics model: NeuroIsing, which has been designed to execute in parallel on a vendor-independent graphics card. Originally introduced in the paper [C.~A.~Zapart, ``Econophysics in Financial Time Series Prediction'', PhD thesis, Graduate University for Advanced Studies, Japan (2009)], at first it was implemented on a CELL processor running inside a SONY PS3 games console. The NeuroIsing framework can be applied to predicting and trading foreign exchange as well as stock market index futures.

The Neuro-Image: Alain Resnais's Digital Cinema without the Digits

NARCIS (Netherlands)

Pisters, P.

2011-01-01

This paper proposes to read cinema in the digital age as a new type of image, the neuroimage. Going back to Gilles Deleuze's cinema books and it is argued that the neuro-image is based in the future. The cinema of Alain Resnais is analyzed as a neuro-image and digital cinema .

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

Science.gov (United States)

Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav

2018-05-18

Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

Determination of the Main Influencing Factors on Road Fatalities Using an Integrated Neuro-Fuzzy Algorithm

Directory of Open Access Journals (Sweden)

Amir Masoud Rahimi

Full Text Available Abstract This paper proposed an integrated algorithm of neuro-fuzzy techniques to examine the complex impact of socio-technical influencing factors on road fatalities. The proposed algorithm could handle complexity, non-linearity and fuzziness in the modeling environment due to its mechanism. The Neuro-fuzzy algorithm for determination of the potential influencing factors on road fatalities consisted of two phases. In the first phase, intelligent techniques are compared for their improved accuracy in predicting fatality rate with respect to some socio-technical influencing factors. Then in the second phase, sensitivity analysis is performed to calculate the pure effect on fatality rate of the potential influencing factors. The applicability and usefulness of the proposed algorithm is illustrated using the data in Iran provincial road transportation systems in the time period 2012-2014. Results show that road design improvement, number of trips, and number of passengers are the most influencing factors on provincial road fatality rate.

Life on the line: the therapeutic potentials of computer-mediated conversation.

Science.gov (United States)

Miller, J K; Gergen, K J

1998-04-01

In what ways are computer networking practices comparable to face-to-face therapy? With the exponential increase in computer-mediated communication and the increasing numbers of people joining topically based computer networks, the potential for grass-roots therapeutic (or antitherapeutic) interchange is greatly augmented. Here we report the results of research into exchanges on an electronic bulletin board devoted to the topic of suicide. Over an 11-month period participants offered each other valuable resources in terms of validation of experience, sympathy, acceptance, and encouragement. They also asked provocative questions and furnished broad-ranging advice. Hostile entries were rare. However, there were few communiques that parallel the change-inducing practices more frequent within many therapeutic settings. In effect, on-line dialogues seemed more sustaining than transforming. Further limits and potentials of on-line communication are explored.

Uncommon presentation of neuro- cysticercosis

African Journals Online (AJOL)

Uncommon presentation of neuro- cysticercosis. Neurocysticercosis (NCC) is a common parasitic infection of the central nervous system caused by the pork tapeworm Taenia solium. The clinical presentation of NCC in children includes generalised and partial seizures with or without features of raised intracranial pressure.

Optimization of Neuro-Fuzzy System Using Genetic Algorithm for Chromosome Classification

Directory of Open Access Journals (Sweden)

M. Sarosa

2013-09-01

Full Text Available Neuro-fuzzy system has been shown to provide a good performance on chromosome classification but does not offer a simple method to obtain the accurate parameter values required to yield the best recognition rate. This paper presents a neuro-fuzzy system where its parameters can be automatically adjusted using genetic algorithms. The approach combines the advantages of fuzzy logic theory, neural networks, and genetic algorithms. The structure consists of a four layer feed-forward neural network that uses a GBell membership function as the output function. The proposed methodology has been applied and tested on banded chromosome classification from the Copenhagen Chromosome Database. Simulation result showed that the proposed neuro-fuzzy system optimized by genetic algorithms offers advantages in setting the parameter values, improves the recognition rate significantly and decreases the training/testing time which makes genetic neuro-fuzzy system suitable for chromosome classification.

Therapeutic potential of carbohydrates as regulators of macrophage activation.

Science.gov (United States)

Lundahl, Mimmi L E; Scanlan, Eoin M; Lavelle, Ed C

2017-12-15

It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants. Although there are numerous endogenous and exogenous factors that have an impact on the macrophage polarisation spectrum, this review will focus specifically on prominent macrophage-modulating carbohydrate motifs with a view towards highlighting structure-function relationships and therapeutic potential. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of ethics in data governance of large neuro-ICT projects.

Science.gov (United States)

Stahl, Bernd Carsten; Rainey, Stephen; Harris, Emma; Fothergill, B Tyr

2018-05-14

We describe current practices of ethics-related data governance in large neuro-ICT projects, identify gaps in current practice, and put forward recommendations on how to collaborate ethically in complex regulatory and normative contexts. We undertake a survey of published principles of data governance of large neuro-ICT projects. This grounds an approach to a normative analysis of current data governance approaches. Several ethical issues are well covered in the data governance policies of neuro-ICT projects, notably data protection and attribution of work. Projects use a set of similar policies to ensure users behave appropriately. However, many ethical issues are not covered at all. Implementation and enforcement of policies remain vague. The data governance policies we investigated indicate that the neuro-ICT research community is currently close-knit and that shared assumptions are reflected in infrastructural aspects. This explains why many ethical issues are not explicitly included in data governance policies at present. With neuro-ICT research growing in scale, scope, and international involvement, these shared assumptions should be made explicit and reflected in data governance.

Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig.

Science.gov (United States)

Wei, Lihua; Ge, Li; Qin, Shucun; Shi, Yunzhi; Du, Changqing; Du, Hui; Liu, Liwei; Yu, Yang; Sun, Xuejun

2012-01-01

Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

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Irune Diaz-Aparicio

2016-01-01

Full Text Available Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct observation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic cells, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neurological disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.

Investigation of elemental changes in brain tissues following excitotoxic injury

International Nuclear Information System (INIS)

Siegele, Rainer; Howell, Nicholas R.; Callaghan, Paul D.; Pastuovic, Zeljko

2013-01-01

Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca +2 cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca +2 cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma

Investigation of elemental changes in brain tissues following excitotoxic injury

Energy Technology Data Exchange (ETDEWEB)

Siegele, Rainer, E-mail: rns@ansto.gov.au [Institute for Environmental Research, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Howell, Nicholas R.; Callaghan, Paul D. [Life Sciences, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Pastuovic, Zeljko [Institute for Environmental Research, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia)

2013-07-01

Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca{sup +2} cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca{sup +2} cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma.

Antibody-based investigational approaches in neuro-proteomics and neurodegenerative diseases

Czech Academy of Sciences Publication Activity Database

Gadher, S. J.; Kovářová, Hana

2015-01-01

Roč. 78, Suppl 2 (2015), s. 10-10 ISSN 1210-7859. [Conference on Animal Models for neuro degenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : neuro degeneration * disease models * multiplexing Subject RIV: EB - Genetics ; Molecular Biology

Neuro-Behçet hos en kaukasid dansk patient

DEFF Research Database (Denmark)

Karshena, Ali; Koch-Henriksen, Nils

2010-01-01

. The diagnosis of neuro-Behçet can be difficult to establish if the mucocutaneous involvement is incomplete, absent, or unattended. We present an exceptional case of neuro-Behçet in a 38-year-old Caucasian Danish woman. On account of the risk of serious complication, it is important to make the diagnosis as soon...

Therapeutic potential of adult stem cells

DEFF Research Database (Denmark)

Serakinci, Nedime; Keith, W. Nicol

2006-01-01

is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple...... lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem...... cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest...

[Establishment of diagnosis and treatment patterns of holistic integrated medicine for neuro-ophthalmology].

Science.gov (United States)

Wang, Yanling

2014-12-01

Neuro-ophthalmology, as an interdisciplinary, covers at least three disciplines- ophthalmology, neurology and neurosurgery. With limited knowledge in each discipline, doctors often make misdiagnoses for neuro-ophthalmology diseases. Therefore, it is imperative to abandon the distinction between disciplines and combine all the knowledge to diagnose and treat patients in patterns of holistic integrated medicine in order to effectively improve the diagnosis and treatment of neuro-ophthalmology.

Potential Therapeutic Effects of Psilocybin.

Science.gov (United States)

Johnson, Matthew W; Griffiths, Roland R

2017-07-01

Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism.

Science.gov (United States)

Phan, Chia-Wei; David, Pamela; Naidu, Murali; Wong, Kah-Hui; Sabaratnam, Vikineswary

2015-01-01

Mushrooms have long been used not only as food but also for the treatment of various ailments. Although at its infancy, accumulated evidence suggested that culinary-medicinal mushrooms may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Therefore, efforts have been devoted to a search for more mushroom species that may improve memory and cognition functions. Such mushrooms include Hericium erinaceus, Ganoderma lucidum, Sarcodon spp., Antrodia camphorata, Pleurotus giganteus, Lignosus rhinocerotis, Grifola frondosa, and many more. Here, we review over 20 different brain-improving culinary-medicinal mushrooms and at least 80 different bioactive secondary metabolites isolated from them. The mushrooms (either extracts from basidiocarps/mycelia or isolated compounds) reduced beta amyloid-induced neurotoxicity and had anti-acetylcholinesterase, neurite outgrowth stimulation, nerve growth factor (NGF) synthesis, neuroprotective, antioxidant, and anti-(neuro)inflammatory effects. The in vitro and in vivo studies on the molecular mechanisms responsible for the bioactive effects of mushrooms are also discussed. Mushrooms can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro evidence and clinical trials with humans are needed.

NeuroD1: developmental expression and regulated genes in the rodent pineal gland

DEFF Research Database (Denmark)

Muñoz, Estela M; Bailey, Michael J; Rath, Martin F

2007-01-01

NeuroD1/BETA2, a member of the bHLH transcription factor family, is known to influence the fate of specific neuronal, endocrine and retinal cells. We report here that NeuroD1 mRNA is highly abundant in the developing and adult rat pineal gland. Pineal expression begins in the 17-day embryo at which...... time it is also detectable in other brain regions. Expression in the pineal gland increases during the embryonic period and is maintained thereafter at levels equivalent to those found in the cerebellum and retina. In contrast, NeuroD1 mRNA decreases markedly in non-cerebellar brain regions during...... development. Pineal NeuroD1 levels are similar during the day and night, and do not appear to be influenced by sympathetic neural input. Gene expression analysis of the pineal glands from neonatal NeuroD1 knockout mice identifies 127 transcripts that are down-regulated (>twofold, p

Therapeutic monoclonal antibody N-glycosylation - Structure, function and therapeutic potential.

Science.gov (United States)

Cymer, Florian; Beck, Hermann; Rohde, Adelheid; Reusch, Dietmar

2018-03-01

Therapeutic antibodies (IgG-type) contain several post-translational modifications (PTMs) whereby introducing a large heterogeneity, both structural and functional, into this class of therapeutics. Of these modifications, glycosylation in the fragment crystallizable (Fc) region is the most heterogeneous PTM, which can affect the stability of the molecule and interactions with Fc-receptors in vivo. Hence, the glycoform distribution can affect the mode of action and have implications for bioactivity, safety and efficacy of the drug. Main topics of the manuscript include: What factors influence the (Fc) glycan pattern in therapeutic antibodies and how can these glycans be characterized? How does structure of the Fc-glycan relate to function and what methods are available to characterize those functions? Although heterogeneous in their scope, the different sections are intended to combine current knowledge on structure-function correlations of IgG glycan structures with regard to Fc (effector) functions, as well as basic aspects and methodologies for their assessment. Copyright © 2017. Published by Elsevier Ltd.

Catamnesis results of an inpatient neuro-otologic and psychosomatic tinnitus therapy 1-5 years after discharge.

Science.gov (United States)

Schaaf, H; Weiß, S; Hesse, G

2017-02-01

even deteriorated (n = 2) demonstrated increased hearing impairment, requiring hearing aids. During the therapy, particularly, the neuro-otologic counselling, the psychotherapy, and the audio-therapy were experienced as effective. After discharge from hospital, especially, the progressive muscle relaxation according to Jacobsen was continued, as well as psychotherapy. With the corresponding symptomatic suffering, an inpatient hospitalisation and tinnitus therapy with neuro-otologic and psychosomatic alignment can achieve medium-to-high-grade therapeutic effects. This requires a disorder-specific approach, which also includes the elements of neuro-otologic counselling, psychotherapy as well as audio-therapy, and the possibility of providing hearing aids and an approach which aims at the continuation of the therapies experienced as helpful.

The Danish Neuro-Oncology Registry

Directory of Open Access Journals (Sweden)

Hansen S

2016-10-01

Full Text Available Steinbjørn Hansen Department of Oncology, Odense University Hospital and Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark Aim of database: The Danish Neuro-Oncology Registry (DNOR was established by the Danish Neuro-Oncology Group as a national clinical database. It was established for the purpose of supporting research and development in adult patients with primary brain tumors in Denmark. Study population: DNOR has registered clinical data on diagnostics and treatment of all adult patients diagnosed with glioma since January 1, 2009, which numbers approximately 400 patients each year. Main variables: The database contains information about symptoms, presurgical magnetic resonance imaging (MRI characteristics, performance status, surgical procedures, residual tumor on postsurgical MRI, postsurgical complications, diagnostic and histology codes, radiotherapy, and chemotherapy. Descriptive data: DNOR publishes annual reports on descriptive data. During the period of registration, postoperative MRI is performed in a higher proportion of the patients (Indicator II, and a higher proportion of patients have no residual tumor after surgical resection of the primary tumor (Indicator IV. Further data are available in the annual reports. The indicators reflect only minor elements of handling brain tumor patients. Another advantage of reporting indicators is the related multidisciplinary discussions giving a better understanding of what actually is going on, thereby facilitating the work on adjusting the national guidelines in the Danish Neuro-Oncology Group. Conclusion: The establishment of DNOR has optimized the quality in handling primary brain tumor patients in Denmark by reporting indicators and facilitating a better multidisciplinary collaboration at a national level. DNOR provides a valuable resource for research. Keywords: brain neoplasms, brain cancer, glioma, clinical quality indicators

The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

DEFF Research Database (Denmark)

Hudson, Brian D; Ulven, Trond; Milligan, Graeme

2013-01-01

G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

Kleptomania in Patients with Neuro-Behçet's Disease

OpenAIRE

Shugaiv, Erkingül; Kıyat-Atamer, Aslı; Tüzün, Erdem; Kürtüncü, Murat; Baral-Kulaksızoğlu, Işın; Akman Demir, Gülşen

2013-01-01

Objective This study was conducted to characterize the prevalence and clinical features of kleptomania, an impulse control disorder, in patients with Behçet's disease involving the central nervous system. Subjects and Methods Medical records of 350 patients with neuro-Behçet's disease were evaluated, and clinical and neuropsychological features of patients with kleptomania were noted. Results Of the 350 neuro-Behçet's disease patients 6 (1.7%) had presented with symptoms that fulfilled the cr...

Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.

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Diana L Price

2010-11-01

Full Text Available Dementia with Lewy bodies (DLB and Parkinson's Disease (PD are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn. Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR, particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipitated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the

From Patient-Specific Mathematical Neuro-Oncology to Precision Medicine

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Anne eBaldock

2013-04-01

Full Text Available Gliomas are notoriously aggressive, malignant brain tumors that have variable response to treatment. These patients often have poor prognosis, informed primarily by histopathology. Mathematical neuro-oncology (MNO is a young and burgeoning field that leverages mathematical models to predict and quantify response to therapies. These mathematical models can form the basis of modern precision medicine approaches to tailor therapy in a patient-specific manner. Patient specific models (PSMs can be used to overcome imaging limitations, improve prognostic predictions, stratify patients and assess treatment response in silico. The information gleaned from such models can aid in the construction and efficacy of clinical trials and treatment protocols, accelerating the pace of clinical research in the war on cancer. This review focuses on the growing translation of PSM to clinical neuro-oncology. It will also provide a forward-looking view on a new era of patient-specific mathematical neuro-oncology.

5th International Conference on Fuzzy and Neuro Computing

CERN Document Server

Panigrahi, Bijaya; Das, Swagatam; Suganthan, Ponnuthurai

2015-01-01

This proceedings bring together contributions from researchers from academia and industry to report the latest cutting edge research made in the areas of Fuzzy Computing, Neuro Computing and hybrid Neuro-Fuzzy Computing in the paradigm of Soft Computing. The FANCCO 2015 conference explored new application areas, design novel hybrid algorithms for solving different real world application problems. After a rigorous review of the 68 submissions from all over the world, the referees panel selected 27 papers to be presented at the Conference. The accepted papers have a good, balanced mix of theory and applications. The techniques ranged from fuzzy neural networks, decision trees, spiking neural networks, self organizing feature map, support vector regression, adaptive neuro fuzzy inference system, extreme learning machine, fuzzy multi criteria decision making, machine learning, web usage mining, Takagi-Sugeno Inference system, extended Kalman filter, Goedel type logic, fuzzy formal concept analysis, biclustering e...

Modeling of Activated Sludge Process Using Sequential Adaptive Neuro-fuzzy Inference System

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Mahsa Vajedi

2014-10-01

Full Text Available In this study, an adaptive neuro-fuzzy inference system (ANFIS has been applied to model activated sludge wastewater treatment process of Mobin petrochemical company. The correlation coefficients between the input variables and the output variable were calculated to determine the input with the highest influence on the output (the quality of the outlet flow in order to compare three neuro-fuzzy structures with different number of parameters. The predictions of the neuro-fuzzy models were compared with those of multilayer artificial neural network models with similar structure. The comparison indicated that both methods resulted in flexible, robust and effective models for the activated sludge system. Moreover, the root mean square of the error for neuro-fuzzy and neural network models were 5.14 and 6.59, respectively, which means the former is the superior method.

The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning

OpenAIRE

Lin, Chin-Hsing; Hansen, Stacey; Wang, Zhenshan; Storm, Daniel R.; Tapscott, Stephen J.; Olson, James M.

2005-01-01

The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this region. NeuroD2 heterozygous mice show profound deficits in emotional learning as assessed by fear conditioning. Unconditioned fear was also diminished in neuroD2 heterozygotes compared to wild-type controls. Several key molecular regulators ...

Neuro-fuzzy models for systems identification applied to the operation of nuclear power plants; Sistemas neuro-fuzzy para identificacao de sistemas aplicados a operacao de centrais nucleares

Energy Technology Data Exchange (ETDEWEB)

Alves, Antonio Carlos Pinto Dias

2000-09-01

A nuclear power plant has a myriad of complex system and sub-systems that, working cooperatively, make the control of the whole plant. Nevertheless their operation be automatic most of the time, the integral understanding of their internal- logic can be away of the comprehension of even experienced operators because of the poor interpretability those controls offer. This difficulty does not happens only in nuclear power plants but in almost every a little more complex control system. Neuro-fuzzy models have been used for the last years in a attempt of suppress these difficulties because of their ability of modelling in linguist form even a system which behavior is extremely complex. This is a very intuitive human form of interpretation and neuro-fuzzy model are gathering increasing acceptance. Unfortunately, neuro-fuzzy models can grow up to become of hard interpretation because of the complexity of the systems under modelling. In general, that growing occurs in function of redundant rules or rules that cover a very little domain of the problem. This work presents an identification method for neuro-fuzzy models that not only allows models grow in function of the existent complexity but that beforehand they try to self-adapt to avoid the inclusion of new rules. This form of construction allowed to arrive to highly interpretative neuro-fuzzy models even of very complex systems. The use of this kind of technique in modelling the control of the pressurizer of a PWR nuclear power plant allowed verify its validity and how neuro-fuzzy models so built can be useful in understanding the automatic operation of a nuclear power plant. (author)

NeuroSPECT assessment of ischemic penumbra in acute brain infarct: control of intra-arterial thrombolysis

International Nuclear Information System (INIS)

Mena, F.J.; Mena, I.; Contreras, I.; Soto, F.; Ducci, H.; Fruns, M.

2002-01-01

Introduction: Brain infarct is the most common cause of incapacity in adults, the second cause of dementia and the 2nd or 3rd cause of death. Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis in the first hours of evolution. Thrombolysis is now an approved and efficacious method of treatment for acute ischemic stroke. During the first 3 hours of evolution, intravenous administration of plasminogen activator (tPA) can be performed. The window of time of treatment is expanded to 6 hours with the intra-arterial super selective route for thrombolysis. Aim: The aim of this study was to define levels of reversible ischemia (penumbra) demonstrated by statistically evaluated HMPAO Tc99m NeuroSPECT performed before and after intra-arterial thrombolysis in the treatment of acute infarct. Materials and Methods: 21 patients were treated during the first 6 hours of evolution of an acute ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan to rule hemorrhage or established infarct. 3) I.V injection of 1100MBq Tc99m HMPAO (Ceretec tm) 4) Conventional cerebral angiography and intra-arterial thrombolysis and/or angioplasty/stenting if necessary. 5) NeuroSPECT assessment of ischemic penumbra. 6) Control at 24 hrs with NeuroSPECT. NeuroSPECT image acquisition is performed immediately following arterial thrombolysis with a dual Head Camera, SHR collimators and conventional protocol. Image processing was performed using the Segami Software, as previously reported in Alasbimn Journal2 (7): April 2000. http://www.alasbimnjournal.cl. The analysis consists of 1) Tallairach brain volume normalization. 2) Voxel by voxel comparison of the individual brain cortex uptake normalized to the maximum in the cortex with a normal database of 24 age-matched controls. Results: The results are expressed in standard deviations (S.D.) below the normal mean. Normal mean is 72% + 6. Only voxels between

Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis.

Science.gov (United States)

Nemoto, Kiyotaka; Dan, Ippeita; Rorden, Christopher; Ohnishi, Takashi; Tsuzuki, Daisuke; Okamoto, Masako; Yamashita, Fumio; Asada, Takashi

2011-01-25

A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites.

Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

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Sabrina Lusvarghi

2016-10-01

Full Text Available Griffithsin (GRFT, an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.

Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases

Science.gov (United States)

de Souza, Jessica M.; Goncalves, Bruno D. C.; Gomez, Marcus V.; Vieira, Luciene B.; Ribeiro, Fabiola M.

2018-01-01

Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death. Venoms are fruitful natural sources of new molecules, which have been relentlessly enhanced by evolution through natural selection. Several studies indicate that venom components can exhibit selectivity and affinity for a wide variety of targets in mammalian systems. For instance, an expressive number of natural peptides identified in venoms from animals, such as snakes, scorpions, bees, and spiders, were shown to lessen inflammation, regulate glutamate release, modify neurotransmitter levels, block ion channel activation, decrease the number of protein aggregates, and increase the levels of neuroprotective factors. Thus, these venom components hold potential as therapeutic tools to slow or even halt neurodegeneration. However, there are many technological issues to overcome, as venom peptides are hard to obtain and characterize and the amount obtained from natural sources is insufficient to perform all the necessary experiments and tests. Fortunately, technological improvements regarding heterologous protein expression, as well as peptide chemical synthesis will help to provide enough quantities and allow chemical and pharmacological enhancements of these natural occurring compounds. Thus, the main focus of this review is to highlight the most promising studies evaluating animal toxins as therapeutic tools to treat a wide variety of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, brain

Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?

Science.gov (United States)

Gopalakrishnan, Ranganath; Frolov, Andrey I; Knerr, Laurent; Drury, William J; Valeur, Eric

2016-11-10

Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.

GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization

Science.gov (United States)

Scandolera, Amandine; Hubert, Jane; Humeau, Anne; Lambert, Carole; De Bizemont, Audrey; Winkel, Chris; Kaouas, Abdelmajid; Renault, Jean-Hugues; Reynaud, Romain

2018-01-01

The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract

GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization

Directory of Open Access Journals (Sweden)

Amandine Scandolera

2018-03-01

Full Text Available The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae. Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR. An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1 receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus

Neuro-oncology Thallium 201 interest

International Nuclear Information System (INIS)

Guyot, M.; Latry, C.; Basse-Cathalinat, B.; Ducassou, D.; Guerin, J.; Maire, J.P.

1994-01-01

So and in spite of its histologic specificity absence, Tl 201 has an evident interest in neuro-oncology: for the low grade astrocytoma transformation diagnosis toward one higher grad; for the neoplasm residue and recidive diagnosis; and more generally as forecasted evolution element during the therapy. 2 figs., 4 tabs., 4 graphs

Progranulin as a biomarker and potential therapeutic agent.

Science.gov (United States)

Abella, Vanessa; Pino, Jesús; Scotece, Morena; Conde, Javier; Lago, Francisca; Gonzalez-Gay, Miguel Angel; Mera, Antonio; Gómez, Rodolfo; Mobasheri, Ali; Gualillo, Oreste

2017-10-01

Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Garlic: a review of potential therapeutic effects

Science.gov (United States)

Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

2014-01-01

Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

Low-dimensional models of ‘Neuro-glio-vascular unit’ for describing neural dynamics under normal and energy-starved conditions

Directory of Open Access Journals (Sweden)

Karishma eChhabria

2016-03-01

Full Text Available The motivation of developing simple minimal models for neuro-glio-vascular system arises from a recent modeling study elucidating the bidirectional information flow within the neuro-glio-vascular system having 89 dynamic equations (Chander and Chakravarthy 2012. While this was one of the first attempts at formulating a comprehensive model for neuro-glia-vascular system, it poses severe restrictions in scaling up to network levels. On the contrary, low dimensional models are convenient devices in simulating large networks that also provide an intuitive understanding of the complex interactions occurring within the neuro-glio-vascular system. The key idea underlying the proposed models is to describe the glio-vascular system as a lumped system which takes neural firing rate as input and returns an ‘energy’ variable (analogous to ATP as output. To this end we present two models: Biophysical neuro-energy (Model #1 with 5 variables, comprising of KATP channel activity governed by neuronal ATP dynamics and the Dynamic threshold (Model #2 with 3 variables depicting the dependence of neural firing threshold on the ATP dynamics. Both the models show different firing regimes such as continuous spiking, phasic and tonic bursting depending on the ATP production coefficient, εp and external current. We then demonstrate that in a network comprising of such energy-dependent neuron units, εp could modulate the Local field potential (LFP frequency and amplitude. Interestingly, low frequency LFP dominates under low εp conditions, which is thought to be reminiscent of seizure-like activity observed in epilepsy. The proposed ‘neuron-energy’ unit may be implemented in building models of neuro-glio-vascular networks to simulate data obtained from multimodal neuroimaging systems such as fNIRS-EEG and fMRI-EEG. Such models could also provide a theoretical basis for devising optimal neurorehabilitation strategies such as non-invasive brain stimulation for

Neuro-oxidative-nitrosative stress in sepsis

DEFF Research Database (Denmark)

Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

2011-01-01

Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

The UC Davis/NIH NeuroMab Facility

Data.gov (United States)

Federal Laboratory Consortium — The mission of the UC Davis/NIH NeuroMab facility is to generate and distribute high quality, validated mouse monoclonal antibodies against molecular targets found...

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

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Sathish Sundar Dhilip Kumar

2018-04-01

Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

Science.gov (United States)

Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

2018-04-05

Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Directory of Open Access Journals (Sweden)

Anke Höllig

2014-10-01

Full Text Available Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last decades more and more reports demonstrated neuroprotective and organoprotective effects. Recent studies predominately use in vivo or in vitro models for ischemic pathologies to investigate the effect of argon treatment. Promising data has been published concerning pathologies like cerebral ischemia, traumatic brain injury and hypoxic ischemic encephalopathy. However, models applied and administration of the therapeutic gas vary. Here we provide a systematic review to summarize the available data on argon’s neuro- and organoprotective effects and discuss its possible mechanism of action. We aim to provide a summary to allow further studies with a more homogeneous setting to investigate possible clinical applications of argon.

Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

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Shih-Chang Chien

2015-01-01

Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

Neuro-Spect and neuropsychological test in the differential diagnosis of dementia

International Nuclear Information System (INIS)

Marroni, B.M.; Louzada, A.G.; Andrea, S.A.; Raupp, A.A.; Sprinz, C.S.; Marroni, S.M.; Canani, L.C.; Zagoury, E.Z.; Borneman, C.B.

2002-01-01

Background/Aim: The role of the Neuro-Spect scintigraphy as a diagnostic tool in central nervous system diseases is well established. However, the simultaneous application of a neuro-psychological test (NPT) may be used to enhance the diagnostic accuracy of the test. The aim of this study was to test if the concomitant use of the NPT may be used to improve the differential diagnostic accuracy of the scintigraphy. Methods: A total of 144 cerebral perfusion studies (CPS) (Tc-ECD, 1110 MBq) were performed between March and October 2001. From this total 63 patients with non-specific complains of memory loss formed the study group. Patients with cancer, psychiatric disturbs or craniotomies were excluded. For analysis the patients were divided in 3 subgroups according to the major complain: a) memory deficit, b) depression and C) organic syndrome that included patients with cerebral stroke, occult hydrocephalus and head trauma. All patients submitted to the Neuro-Spect underwent a simultaneous NPT. The NPT included the following tests: Digit Span (WAIS-R), verbal fluency, clock drawing task, Minimental State Examination (MMSE) and Rey Auditory Verbal Learning Test (RAVLT). Well-established criteria, such as symmetry and concentration of the Tc-ECD were used for evaluation of the CPS. Concordance of the findings in the CPS and the anatomic lesion was used to reinforce the final conclusions. A scale for Alzheimer's Like Dementia (ALD) from 1 to 8 was developed (where 1=normal and 8 suggests ALD) using as reference the study of Holmann BL. Results: The NPT showed a positive correlation with the Neuro-Spect's probability scale. The tests with the best correlation were the verbal fluency (p<0.001), RAVLT and the memory recall (p<0.01). The MMSE did not show association with the Neuro-Spect probability scale. Conclusions: There is a positive association between the NPT and the Neuro-Spect. These results suggest that the NPT added to the Neuro-Spect may the be useful in the

Clinical neuro-oncology formal education opportunities for medical students in the United States and Canada.

Science.gov (United States)

Dixit, Karan S; Nicholas, Martin Kelly; Lukas, Rimas V

2014-12-01

To develop an understanding of the availability of the formal clinical neuro-oncology educational opportunities for medical students. The curriculum websites of all medical schools accredited by the Liaison Committee on Medical Education were reviewed for the presence of clinical neuro-oncology electives as well as other relevant data. Ten (6.8%) of medical schools accredited by the Liaison Committee on Medical Education offer formal neuro-oncology electives. Half are clustered in the Midwest. Forty percent are at institutions with neuro-oncology fellowships. All are at institutions with neurosurgery and neurology residency programs. Formal clinical neuro-oncology elective opportunities for medical students in the United States and Canada are limited. Additional such opportunities may be of value in the education of medical students. Copyright © 2014 Elsevier Inc. All rights reserved.

ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.

Science.gov (United States)

Bonafede, Roberta; Mariotti, Raffaella

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.

NeuroMind : Past, present, and future

NARCIS (Netherlands)

Kubben, Pieter L

2017-01-01

This narrative report describes the underlying rationale and technical developments of NeuroMind, a mobile clinical decision support system for neurosurgery. From the perspective of a neurosurgeon - (app) developer it explains how technical progress has shaped the world's "most rated and highest

Translational research in NeuroAIDS: a neuroimmune pharmacology-related course.

Science.gov (United States)

Brown, Amanda; Shiramizu, Bruce; Nath, Avindra; Wojna, Valerie

2011-03-01

Neuroimmune pharmacology (NIP) can be considered a multidisciplinary science where areas of neuroscience, immunology, and pharmacology intersect in neurological disorders. The R25 training program titled "Translational Research in NeuroAIDS and Mental Health (TR-NAMH): An innovative mentoring program to promote diversity in NeuroAIDS Research (R25 MH080661)" at the Johns Hopkins University is a web-based interactive course with the goal to improve the capacity of high quality research by developing mentoring programs for (1) doctoral and postdoctoral candidates and junior faculty from racial and ethnic minorities and (2) non-minority individuals at the same levels, whose research focuses on NeuroAIDS disparity issues such as HIV-associated neurocognitive disorders (HAND). This web-based interactive course overcomes the limitations of traditional education such as access to expert faculty and financial burden of scientists from racial and ethnic minority groups in the field of NeuroAIDS research and NIP and identifies rich nurturing environments for investigators to support their careers. The TR-NAMH program identifies a cadre of talented students and investigators eager to commit to innovative educational and training sessions in NeuroAIDS and NIP. The interplay between NIP changes precipitated by HIV infection in the brain makes the study of HAND an outstanding way to integrate important concepts from these two fields. The course includes activities besides those related to didactic learning such as research training and long-term mentoring; hence, the newly learned topics in NIP are continually reinforced and implemented in real-time experiences. We describe how NIP is integrated in the TR-NAMH program in the context of HAND.

Adaptive neuro-fuzzy inference systems (ANFIS) application to investigate potential use of natural ventilation in new building designs in Turkey

Energy Technology Data Exchange (ETDEWEB)

Ayata, Tahir; Cam, Ertugrul; Yildiz, Osman [Kirikkale University, Faculty of Engineering, 71451, Campus, Kirikkale (Turkey)

2007-05-15

Natural ventilation in living and working places provides both circulation of clear air and a decrease of indoor temperature, especially during hot summer days. In addition to openings, the dimension ratio and position of buildings play a significant role to obtain a uniform indoor air velocity distribution. In this study, the potential use of natural ventilation as a passive cooling system in new building designs in Kayseri, a midsize city in Turkey, was investigated. First, indoor air velocity distributions with respect to changing wind direction and magnitude were simulated by the FLUENT package program, which employs finite element methods. Then, an adaptive neuro-fuzzy inference systems (ANFIS) model was employed to predict indoor average and maximum air velocities using the simulated data by FLUENT. The simulation results suggest that natural ventilation can be used to provide a thermally comfortable indoor environment during the summer season in the study area. Also, the ANFIS model can be proposed for estimation of indoor air velocity values in such studies. (author)

Evidence-based Neuro Linguistic Psychotherapy: a meta-analysis.

Science.gov (United States)

Zaharia, Cătălin; Reiner, Melita; Schütz, Peter

2015-12-01

Neuro Linguistic Programming (NLP) Framework has enjoyed enormous popularity in the field of applied psychology. NLP has been used in business, education, law, medicine and psychotherapy to identify people's patterns and alter their responses to stimuli, so they are better able to regulate their environment and themselves. NLP looks at achieving goals, creating stable relationships, eliminating barriers such as fears and phobias, building self-confidence, and self-esteem, and achieving peak performance. Neuro Linguistic Psychotherapy (NLPt) encompasses NLP as framework and set of interventions in the treatment of individuals with different psychological and/or social problems. We aimed systematically to analyse the available data regarding the effectiveness of Neuro Linguistic Psychotherapy (NLPt). The present work is a meta-analysis of studies, observational or randomized controlled trials, for evaluating the efficacy of Neuro Linguistic Programming in individuals with different psychological and/or social problems. The databases searched to identify studies in English and German language: CENTRAL in the Cochrane Library; PubMed; ISI Web of Knowledge (include results also from Medline and the Web of Science); PsycINFO (including PsycARTICLES); Psyndex; Deutschsprachige Diplomarbeiten der Psychologie (database of theses in Psychology in German language), Social SciSearch; National library of health and two NLP-specific research databases: one from the NLP Community (http://www.nlp.de/cgi-bin/research/nlprdb.cgi?action=res_entries) and one from the NLP Group (http://www.nlpgrup.com/bilimselarastirmalar/bilimsel-arastirmalar-4.html#Zweig154). From a total number of 425 studies, 350 were removed and considered not relevant based on the title and abstract. Included, in the final analysis, are 12 studies with numbers of participants ranging between 12 and 115 subjects. The vast majority of studies were prospective observational. The actual paper represents the first

Date Palm Tree (Phoenix dactylifera L.: Natural Products and Therapeutic Options

Directory of Open Access Journals (Sweden)

Reem A. Al-Alawi

2017-05-01

Full Text Available Many plants, including some of the commonly consumed herbs and spices in our daily food, can be safely and effectively used to prevent and/or treat some health concerns. For example, caffeine the active ingredient found in coffee beans (Coffea, shows biological activity in the treatment of the central nervous system (CNS disorders, indole-3-carbinol, and 3,3′-diindolylmethane are both broccoli (Brassica oleracea derived phytochemicals with potential anti-cancer activity, and resveratrol, isolated from grape (Vitis vinifera, is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects. Date palm fruits possess high nutritional and therapeutic value with significant antioxidant, antibacterial, antifungal, and anti-proliferative properties. This review focuses on the date fruit extracts and their benefits in individual health promoting conditions and highlights their applications as useful to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial products.

Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J

2001-01-01

) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed...... by fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity...

Neuro-fuzzy controller to navigate an unmanned vehicle.

Science.gov (United States)

Selma, Boumediene; Chouraqui, Samira

2013-12-01

A Neuro-fuzzy control method for an Unmanned Vehicle (UV) simulation is described. The objective is guiding an autonomous vehicle to a desired destination along a desired path in an environment characterized by a terrain and a set of distinct objects, such as obstacles like donkey traffic lights and cars circulating in the trajectory. The autonomous navigate ability and road following precision are mainly influenced by its control strategy and real-time control performance. Fuzzy Logic Controller can very well describe the desired system behavior with simple "if-then" relations owing the designer to derive "if-then" rules manually by trial and error. On the other hand, Neural Networks perform function approximation of a system but cannot interpret the solution obtained neither check if its solution is plausible. The two approaches are complementary. Combining them, Neural Networks will allow learning capability while Fuzzy-Logic will bring knowledge representation (Neuro-Fuzzy). In this paper, an artificial neural network fuzzy inference system (ANFIS) controller is described and implemented to navigate the autonomous vehicle. Results show several improvements in the control system adjusted by neuro-fuzzy techniques in comparison to the previous methods like Artificial Neural Network (ANN).

Neuro-genetic system for optimization of GMI samples sensitivity.

Science.gov (United States)

Pitta Botelho, A C O; Vellasco, M M B R; Hall Barbosa, C R; Costa Silva, E

2016-03-01

Magnetic sensors are largely used in several engineering areas. Among them, magnetic sensors based on the Giant Magnetoimpedance (GMI) effect are a new family of magnetic sensing devices that have a huge potential for applications involving measurements of ultra-weak magnetic fields. The sensitivity of magnetometers is directly associated with the sensitivity of their sensing elements. The GMI effect is characterized by a large variation of the impedance (magnitude and phase) of a ferromagnetic sample, when subjected to a magnetic field. Recent studies have shown that phase-based GMI magnetometers have the potential to increase the sensitivity by about 100 times. The sensitivity of GMI samples depends on several parameters, such as sample length, external magnetic field, DC level and frequency of the excitation current. However, this dependency is yet to be sufficiently well-modeled in quantitative terms. So, the search for the set of parameters that optimizes the samples sensitivity is usually empirical and very time consuming. This paper deals with this problem by proposing a new neuro-genetic system aimed at maximizing the impedance phase sensitivity of GMI samples. A Multi-Layer Perceptron (MLP) Neural Network is used to model the impedance phase and a Genetic Algorithm uses the information provided by the neural network to determine which set of parameters maximizes the impedance phase sensitivity. The results obtained with a data set composed of four different GMI sample lengths demonstrate that the neuro-genetic system is able to correctly and automatically determine the set of conditioning parameters responsible for maximizing their phase sensitivities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polyphenolic compounds with antioxidant potential and neuro-protective effect from Cimicifuga dahurica (Turcz.) Maxim.

Science.gov (United States)

Qin, Rulan; Zhao, Ying; Zhao, Yudan; Zhou, Wanrong; Lv, Chongning; Lu, Jincai

2016-12-01

Three new phenolic compounds (1-3), along with five known compounds (4-8) were isolated from the rhizome of Cimicifuga dahurica (Turcz.) Maxim. Their structures were elucidated by spectroscopic methods including 1D-NMR, 2D-NMR and HR-MS techniques. DPPH method and protective effect on PC12 cells against H 2 O 2 -induced oxidative damage model were carried to evaluate the antioxidant capability of these compounds. Compound 5 showed significant antioxidant activity with IC 50 values 9.33μM in DPPH assay and compound 2 displayed marked neuro-protective effect with 87.65% cell viability at the concentration of 10μM. Additionally, the possible structure-activity relationships of these phenolic compounds were tentatively discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism

Directory of Open Access Journals (Sweden)

Perrella Joel

2005-05-01

Full Text Available Abstract Background High concentrations of glutamate can accumulate in the brain and may be involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. This form of neurotoxicity involves changes in the regulation of cellular calcium (Ca2+ and generation of free radicals such as peroxynitrite (ONOO-. Estrogen may protect against glutamate-induced cell death by reducing the excitotoxic Ca2+ influx associated with glutamate excitotoxicity. In this study, the inhibition of N-methyl-D-aspartate (NMDA receptor and nitric oxide synthase (NOS along with the effect of 17β-estradiol (17β-E2 and a more potent antioxidant Δ8, 17β-estradiol (Δ8, 17β-E2 on cell viability and intracellular Ca2+ ([Ca2+]i, following treatment of rat cortical cells with glutamate, was investigated. Results Primary rat cortical cells were cultured for 7–12 days in Neurobasal medium containing B27 supplements. Addition of glutamate (200 μM decreased cell viability to 51.3 ± 0.7% compared to control. Treatment with the noncompetitive NMDAR antagonist, MK-801, and the NOS inhibitor, L-NAME, completely prevented cell death. Pretreatment (24 hrs with 17β-E2 and Δ8, 17β-E2 (0.01 to 10 μM significantly reduced cell death. 17β-E2 was more potent than Δ8, 17β-E2. Glutamate caused a rapid 2.5 fold increase in [Ca2+]i. Treatment with 0.001 to 10 μM MK-801 reduced the initial Ca2+ influx by 14–41% and increased cell viability significantly. Pretreatment with 17β-E2 and Δ8, 17β-E2 had no effect on Ca2+ influx but protected the cortical cells against glutamate-induced cell death. Conclusion Glutamate-induced cell death in cortical cultures can occur through NMDAR and NOS-linked mechanisms by increasing nitric oxide and ONOO-. Equine estrogens: 17β-E2 and Δ8, 17β-E2, significantly protected cortical cells against glutamate-induced excitotoxicity by a mechanism that appears to be independent of Ca2+ influx. To our knowledge, this is a first

Validation of the Neuro-QoL measurement system in children with epilepsy.

Science.gov (United States)

Lai, Jin-Shei; Nowinski, Cindy J; Zelko, Frank; Wortman, Katy; Burns, James; Nordli, Douglas R; Cella, David

2015-05-01

Children with epilepsy often face complex psychosocial consequences that are not fully captured by existing patient-reported outcome (PRO) measures. The Neurology Quality of Life Measurement System "Neuro-QoL" was developed to provide a set of common PRO measures that address issues important to people with neurologic disorders. This paper reports Neuro-QoL (anxiety, depression, interaction with peers, fatigue, pain, cognitive function, stigma, and upper and lower extremity functions) validation in children with epilepsy. Patients (aged 10-18years) diagnosed with epilepsy completed Neuro-QoL and legacy measures at time 1 (initial study visit) and 6-month follow-up. Internal consistency reliability was also evaluated. Concurrent validity was assessed by comparing Neuro-QoL measures with more established "legacy" measures of the same concepts. Clinical validity was evaluated by comparing mean Neuro-QoL scores of patients grouped by clinical anchors such as disease severity. Responsiveness of the Neuro-QoL from time 1 (initial study visit) to 6months was evaluated using self-reported change as the primary anchor. Sixty-one patients (mean age=13.4years; 62.3% male, 75.9% white) participated. Most patients (64.2%) had been seizure-free in the 3months prior to participation, and seizure frequency was otherwise described as follows: 17.8% daily, 13.3% weekly, 35.6% monthly, and 33.3% yearly. All patients were taking antiepileptic drugs. Patients reported better function/less symptoms compared to the reference groups. Internal consistency (alpha) coefficients ranged from 0.76 to 0.87. Patients with different seizure frequencies differed on anxiety (pNeuro-QoL measures were significantly correlated with other measures assessing similar domains. Stigma was related to self-reported change in several areas of functioning but in sometimes unexpected directions. The Neurology Quality of Life Measurement System is a valid and reliable assessment tool for children with epilepsy

Neuro-robotics from brain machine interfaces to rehabilitation robotics

CERN Document Server

Artemiadis

2014-01-01

Neuro-robotics is one of the most multidisciplinary fields of the last decades, fusing information and knowledge from neuroscience, engineering and computer science. This book focuses on the results from the strategic alliance between Neuroscience and Robotics that help the scientific community to better understand the brain as well as design robotic devices and algorithms for interfacing humans and robots. The first part of the book introduces the idea of neuro-robotics, by presenting state-of-the-art bio-inspired devices. The second part of the book focuses on human-machine interfaces for pe

The Effect of Neuro-Linguistic Programming (NLP) on Reading Comprehension in English for Specific Purposes Courses

Science.gov (United States)

Farahani, Fahimeh

2018-01-01

Neuro-Linguistic Programming (NLP) has potential to help language learners; however, it has received scant attention. The present study was an attempt to investigate the effect of NLP techniques on reading comprehension of English as a Foreign Language (EFL) learners at an English for Specific Purposes (ESP) course. To achieve this goal, two…

NeuroFlow: A General Purpose Spiking Neural Network Simulation Platform using Customizable Processors.

Science.gov (United States)

Cheung, Kit; Schultz, Simon R; Luk, Wayne

2015-01-01

NeuroFlow is a scalable spiking neural network simulation platform for off-the-shelf high performance computing systems using customizable hardware processors such as Field-Programmable Gate Arrays (FPGAs). Unlike multi-core processors and application-specific integrated circuits, the processor architecture of NeuroFlow can be redesigned and reconfigured to suit a particular simulation to deliver optimized performance, such as the degree of parallelism to employ. The compilation process supports using PyNN, a simulator-independent neural network description language, to configure the processor. NeuroFlow supports a number of commonly used current or conductance based neuronal models such as integrate-and-fire and Izhikevich models, and the spike-timing-dependent plasticity (STDP) rule for learning. A 6-FPGA system can simulate a network of up to ~600,000 neurons and can achieve a real-time performance of 400,000 neurons. Using one FPGA, NeuroFlow delivers a speedup of up to 33.6 times the speed of an 8-core processor, or 2.83 times the speed of GPU-based platforms. With high flexibility and throughput, NeuroFlow provides a viable environment for large-scale neural network simulation.

Religious Experience from a Neuro-Psychological View

Directory of Open Access Journals (Sweden)

Hadi Vakili

2011-08-01

Full Text Available The search for the basis of religious experience among neurological processes in the brain has resulted in a widespread debate within, as well as outside the academic world. The aim of this paper is to analyze to what extent a neuro-psychological theory could explain the phenomenon of  religious experience. To clarify what the neuro-psychological studies of  the present paper mean by the concept of  religious experience, the concept has been divided into three different types: The Erlebnis or RErl type, the Erfahrung or RErf type and the ideological type of religious experience or RIT type. Furthermore, the present paper is focused on the work of neuro-psychologist M. A. Persinger [1997, 1993, 1992, 1991, 1987, 1985, and 1984]. In his studies, Persinger indicates that mystical experience (RErl has its seat in the right hemisphere of the human brain, whereas (religious ideology (RIT is related to the left hemisphere. Consequently, the hemisphere in which the (religious experience is taking place seems to label the type of experience. Persinger, interested in the powerful effects of religious experience (of the RErf type on human beings, asserts that if we could understand the neuro-cognitive processes involved in experiencing religiously, such processes might be copied for clinical use in order to improve psychiatric therapy for curing depression. Thus, Persinger studied and compared people practicing religious meditation with people who did not, and also studied the results of PET scanning on the experiences of schizophrenic and epileptic patients. PET scanning measures the metabolic activity in the hemispheres, ranging it on a scale from under normal to over normal activity. This paper will account for the relevance of comparing these two apparently different studies and for the problem arising the experience of pain because, neurologically, pain, like religious experience,is said to be caused by processes in the human brain.

Significance of antioxidant potential of plants and its relevance to therapeutic applications.

Science.gov (United States)

Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong

2015-01-01

Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases

Directory of Open Access Journals (Sweden)

Taiwo Betty Ayeleso

2017-11-01

Full Text Available The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases.

A Genetic Based Neuro-Fuzzy Controller System

International Nuclear Information System (INIS)

Mohamed, A.H.

2014-01-01

Recently, the mobile robots have great importance in the manufacturing processes. They are widely used for assembling processes, handling the dangerous components, moving the weighted things, etc. Designing the controller of the mobile robot is a very complex task. Many simple control systems used the neuro-fuzzy controller in the mobile robots. But, they faced with great complexity when moving in unstructured and dynamic environments. The proposed system introduces the uses of the genetic algorithm for optimizing the parameters of the neuro-fuzzy controller. So, the proposed system can improve the performance of the mobile robots. It has applied for a mobile robot used for moving the dangerous and critical materials in unstructured environment. Its results are compared with other traditional controller systems. The suggested system has proved its success for the real-time applications

A Neuro-psychological Explanation of Religious Experience?

DEFF Research Database (Denmark)

Runehov, Anne Leona Cesarine

2004-01-01

and for the problem arising when drawing inadequately reasoned conclusions. Key Words Religious experiences, religious Erlebnis, religious Erfahrung, (religious) ideology, neuroscience, neuropsychology, pain, PET, reductionism, partial reductionism, Transcendental Meditation, epilepsy, schizophrenia.......The search for the basis of religious experience among neurological processes in the brain has resulted in a widespread debate within, as well as outside the academic world. The aim of this paper is to analyse to what extent a neuro-psychological theory could explain the phenomenon of religious...... experience. To clarify what the neuro-psychological studies of the present paper mean by the concept of religious experience, the concept has been divided into three different types: the Erlebnis or RErl type, the Erfahrung or RErf type and the ideological or RIT type of religious experience. In his studies...

Translational Research in NeuroAIDS: A Neuroimmune Pharmacology-Related Course

OpenAIRE

Brown, Amanda; Shiramizu, Bruce; Nath, Avindra; Wojna, Valerie

2010-01-01

Neuroimmune pharmacology (NIP) can be considered a multidisciplinary science where areas of neuroscience, immunology, and pharmacology intersect in neurological disorders. The R25 training program titled “Translational Research in NeuroAIDS and Mental Health (TR-NAMH): An innovative mentoring program to promote diversity in NeuroAIDS Research (R25 MH080661)” at the Johns Hopkins University is a web-based interactive course with the goal to improve the capacity of high quality research by deve...

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

Science.gov (United States)

Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

Closed-loop, multichannel experimentation using the open-source NeuroRighter electrophysiology platform

Directory of Open Access Journals (Sweden)

Jonathan Paul Newman

2013-01-01

Full Text Available Single neuron feedback control techniques, such as voltage clamp and dynamic clamp, have enabled numerous advances in our understanding of ion channels, electrochemical signaling, and neural dynamics. Although commercially available multichannel recording and stimulation systems are commonly used for studying neural processing at the network level, they provide little native support for real-time feedback. We developed the open-source NeuroRighter multichannel electrophysiology hardware and software platform for closed-loop multichannel control with a focus on accessibility and low cost. NeuroRighter allows 64 channels of stimulation and recording for around US $10,000, along with the ability to integrate with other software and hardware. Here, we present substantial enhancements to the NeuroRighter platform, including a redesigned desktop application, a new stimulation subsystem allowing arbitrary stimulation patterns, low-latency data servers for accessing data streams, and a new application programming interface (API for creating closed-loop protocols that can be inserted into NeuroRighter as plugin programs. This greatly simplifies the design of sophisticated real-time experiments without sacrificing the power and speed of a compiled programming language. Here we present a detailed description of NeuroRighter as a stand alone application, its plugin API, and an extensive set of case studies that highlight the system's abilities for conducting closed-loop, multichannel interfacing experiments.

Effect of NeuroD gene silencing on the migration and invasion of human pancreatic cancer cells PANC-1.

Science.gov (United States)

Wang, Yang; Su, Dong Wei; Gao, Li; Ding, Gui Ling; Ni, Can Rong; Zhu, Ming Hua

2014-07-01

The aim of this study is to investigate the influence of Lenti-EGFP-NeuroD-miR, RNAi lentiviral expression vector, on the expression level of NeuroD and migration, and invasion of PANC-1 cell line. PANC-1 cells were cultured and cotransfected with Lenti-EGFP-NeuroD-miR and Lenti-GFP. The infection rate of lentivirus was determined by fluorescence. The interfering effection by the expression of NeuroD mRNA in PANC-1 cells was analyzed by real-time PCR after transfected. Biological behavior of PANC-1 cells transinfected was observed, and the migration and invasion were studied by transwell assay. Intrapancreatic allografts model in nude mice was established to observe the effects of NeuroD on tumorigenesis, tumor growth, and invasion in vivo. The expression of NeuroD mRNA decreased significantly after RNAi lentivirus transinfecting PANC-1 cell. The cell's migration and invasion ability decreased obviously as soon as down regulate of NeuroD in PANC-1 cells. Comparing with control group, the tumors were smaller in size and the invasiveness was inhibited after 8 weeks intrapancreatic allografts in nude mice. Lenti-EGFP-NeuroD-miR transfected into PANC-1 cells shows a stable, effective, and especial blocking expression of NeuroD in mRNA level. The RNAi of lentiviral vector target NeuroD can reduce the migration and invasion abilities of PANC-1 cells.

Space Flight-Associated Neuro-ocular Syndrome.

Science.gov (United States)

Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Tarver, William

2017-09-01

New and unique physiologic and pathologic systemic and neuro-ocular responses have been documented in astronauts during and after long-duration space flight. Although the precise cause remains unknown, space flight-associated neuro-ocular syndrome (SANS) has been adopted as an appropriate descriptive term. The Space Medicine Operations Division of the US National Aeronautics and Space Administration (NASA) has documented the variable occurrence of SANS in astronauts returning from long-duration space flight on the International Space Station. These clinical findings have included unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts. The clinical findings of SANS have been correlated with structural changes on intraorbital and intracranial magnetic resonance imaging and in-flight and terrestrial ultrasonographic studies and ocular optical coherence tomography. Further study of SANS is ongoing for consideration of future manned missions to space, including a return trip to the moon or Mars.

NEURO-EPISTEMOLOGY: A POST-MODERNIST ANALYSIS OF ...

African Journals Online (AJOL)

support

ontwikkel die term “neuro-epistemologie” wat die raamwerk vir wetenskaplike studies na die ... In short, this .... This means we run ..... sensory material provided by an external world. .... between short-, intermediate-, and long-term memory.

A novel Neuro-fuzzy classification technique for data mining

Directory of Open Access Journals (Sweden)

Soumadip Ghosh

2014-11-01

Full Text Available In our study, we proposed a novel Neuro-fuzzy classification technique for data mining. The inputs to the Neuro-fuzzy classification system were fuzzified by applying generalized bell-shaped membership function. The proposed method utilized a fuzzification matrix in which the input patterns were associated with a degree of membership to different classes. Based on the value of degree of membership a pattern would be attributed to a specific category or class. We applied our method to ten benchmark data sets from the UCI machine learning repository for classification. Our objective was to analyze the proposed method and, therefore compare its performance with two powerful supervised classification algorithms Radial Basis Function Neural Network (RBFNN and Adaptive Neuro-fuzzy Inference System (ANFIS. We assessed the performance of these classification methods in terms of different performance measures such as accuracy, root-mean-square error, kappa statistic, true positive rate, false positive rate, precision, recall, and f-measure. In every aspect the proposed method proved to be superior to RBFNN and ANFIS algorithms.

Research progress in neuro-immune interactions in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Jin-ling CAI

2012-09-01

Full Text Available The innate immune response may be activated quickly once the organism is invaded by exotic pathogens. An excessive immune response may result in inflammation and tissue damage, whereas an insufficient immune response may result in infection. Nervous system may regulate the intensity of innate immune responses by releasing neurotransmitters, neuropeptides and hormones. Compared with the complicated neuro-immune system in mammals, it is much simpler in Caenorhabditis elegans. Besides, C. elegans is accessible to genetic, molecular biology and behavioral analyses, so it has been used in studies on neuro-immune interactions. It has been revealed recently in the studies with C. elegans that the neuronal pathways regulating innate immune responses primarily include a transforming growth factor-β (TGF-β pathway, an insulin/insulin-like growth factor receptor (IGF pathway and dopaminergic neurotransmission. Since these pathways are evolutionally conservative, so it might be able to provide some new ideas for the research on neuro-immune interactions at molecular levels. The recent progress in this field has been reviewed in present paper.

A Hybrid Neuro-Fuzzy Model For Integrating Large Earth-Science Datasets

Science.gov (United States)

Porwal, A.; Carranza, J.; Hale, M.

2004-12-01

A GIS-based hybrid neuro-fuzzy approach to integration of large earth-science datasets for mineral prospectivity mapping is described. It implements a Takagi-Sugeno type fuzzy inference system in the framework of a four-layered feed-forward adaptive neural network. Each unique combination of the datasets is considered a feature vector whose components are derived by knowledge-based ordinal encoding of the constituent datasets. A subset of feature vectors with a known output target vector (i.e., unique conditions known to be associated with either a mineralized or a barren location) is used for the training of an adaptive neuro-fuzzy inference system. Training involves iterative adjustment of parameters of the adaptive neuro-fuzzy inference system using a hybrid learning procedure for mapping each training vector to its output target vector with minimum sum of squared error. The trained adaptive neuro-fuzzy inference system is used to process all feature vectors. The output for each feature vector is a value that indicates the extent to which a feature vector belongs to the mineralized class or the barren class. These values are used to generate a prospectivity map. The procedure is demonstrated by an application to regional-scale base metal prospectivity mapping in a study area located in the Aravalli metallogenic province (western India). A comparison of the hybrid neuro-fuzzy approach with pure knowledge-driven fuzzy and pure data-driven neural network approaches indicates that the former offers a superior method for integrating large earth-science datasets for predictive spatial mathematical modelling.

Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

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Holub, Justin M

2017-09-01

Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

"Too Withdrawn" or "Too Friendly": Considering Social Vulnerability in Two Neuro-Developmental Disorders

Science.gov (United States)

Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.

2012-01-01

In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neuro-developmental disorders Williams syndrome, characterised by "hypersociability", and autism spectrum disorders, characterised by "social…

Spacecraft attitude control using neuro-fuzzy approximation of the optimal controllers

Science.gov (United States)

Kim, Sung-Woo; Park, Sang-Young; Park, Chandeok

2016-01-01

In this study, a neuro-fuzzy controller (NFC) was developed for spacecraft attitude control to mitigate large computational load of the state-dependent Riccati equation (SDRE) controller. The NFC was developed by training a neuro-fuzzy network to approximate the SDRE controller. The stability of the NFC was numerically verified using a Lyapunov-based method, and the performance of the controller was analyzed in terms of approximation ability, steady-state error, cost, and execution time. The simulations and test results indicate that the developed NFC efficiently approximates the SDRE controller, with asymptotic stability in a bounded region of angular velocity encompassing the operational range of rapid-attitude maneuvers. In addition, it was shown that an approximated optimal feedback controller can be designed successfully through neuro-fuzzy approximation of the optimal open-loop controller.

Ethical considerations of neuro-oncology trial design in the era of precision medicine.

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Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

2017-08-01

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

NEURO ENGINEERING TECHNOLOGY TO ACCELERATE THE HUMAN ADAPTATION TO HIGH ALTITUDE HYPOXIA

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Mukhamed T. Shaov

2018-01-01

Full Text Available Abstract. The aim is to study the influence of neuro-information signals modulated by pulse hypoxia on the rhythm of cardiac contractions in low-mountain and high-mountain conditions. Methods. Heart rate was measured using the pulse oxymetry device ELOX-01M2. The impact analysis of information-wave signals was carried out with the help of the neuro-protector "Anthropotherapist", non-invasively (remotely at a distance of up to 5 meters for 5 min. /day during 10 days. The investigations were carried out in lowmountain conditions (city of Nalchik, 550 m above sea level and highlands, Mount Elbrus (site of "Garabashi", 3780 m. above sea level. Participants in the study were divided into groups: control group – 18 participants; experimental group - 18 participants. In the low-mountain and high-mountain conditions, the control group was not affected by the neuro-protector. In high-mountain conditions, the participants in the control group experienced only the effects of high-altitude hypoxia sessions. The experimental group was exposed to the neuro-information signals from the neuro-protector. High-altitude studies were carried out in the following mode: heart rate was recorded at the altitudes of Nalchik - exit to Elbrus – on the way to the site of "Garabashi" - return route to Nalchik. Results. It was found that with frequency exposure, there is a significant decrease and fluctuations in heart rate in low-mountain inhabitants. The stability of these changes in the rhythm of cardiac activity can also be seen in conditions of high-altitude hypoxia. Conclusion. Consequently, the proposed mode of frequency impact, implemented using the "Anthropotherapist" neuro-protector technology, can form a stage of adaptation to hypoxia and unfavorable climatic and environmental factors.

Sturge-Weber syndrome. The current neuro-imaging data

International Nuclear Information System (INIS)

Boukobza, M.; Cambra, M.R.; Merland, J.J.; Enjolras, O.

2000-01-01

Sturge-Weber syndrome (SWS) is a rare congenital sporadic disease with neuro-ocular and cutaneous vascular findings. Clinically, the full-blown condition consists of a facial port-wine stain (PWS) the V1 facial trigeminal skin area, alone or in combination with V2 and V3 PWS, seizures and ocular abnormalities (glaucoma and choroidal angioma). Radiologically, a leptomeningeal (pial) capillary and venous malformation, mostly located in the parieto-occipital area, cerebral atrophy and calcifications are demonstrated. An ipsilateral enlarged choroid plexus may be an early anatomic symptom. Development neuro-diagnostic technique for the screening of infants with an at-risk V1 PWS, as well as for the follow-up of patients with evidence SWS. Accelerated myelination in the involved hemisphere may be early diagnostic feature before 6 months of age. Later, hyperintensity of white matter on T2 is considered a symptom of gliosis. Clinically, progression of the diseases is associated with anatomic changes and correlates with the extent of the pial vascular anomaly, extent and severity of cerebral atrophy, and white matter abnormalities. A neonatal neuro-imaging work-up, using CT or MRI, may not demonstrate the pial anomaly and should be repeated after 6 to 12 months in an at-risk infant with V1 PWS. (authors)

Development of an Integrated Subspecialist Multidisciplinary Neuro-oncology Service

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Price, Stephen J; Guilfoyle, Mathew; J Jefferies, Sarah; Harris, Fiona; Oberg, Ingela; G Burnet, Neil; Santarius, Thomas; Watts, Colin

2013-01-01

Traditionally, the poor outcome for patients with malignant brain tumours led to therapeutic nihilism. In turn, this resulted in lack of interest in neurosurgical oncology subspecialisation, and less than ideal patient pathways. One problem of concern was the low rate of tumour resection. Between 1997 and 2006, 685 treated glioblastomas were identified. In the first four years only 40% of patients underwent tumour resection, rising to 55% in the last four years. Before revision of the pathway, the median length of hospital stay was 8 days, and 35% of patients received the results of their histology outside of a clinic setting. A pathway of care was established, in which all patients were discussed pre-operatively in an MDT meeting and then directed into a new surgical neuro-oncology clinic providing first point of contact. This limited the number of surgeons operating on adult glioma patients and aided recruitment into research studies. Now, three consultant neurosurgeons run this service, easily fulfilling IOG requirement to spend >50% of programmed activities in neuro-oncology. Nursing support has been critical to provide an integrated service. This model has allowed increased recruitment to clinical trials. The introduction of this service led to an increase in patients discussed pre-operatively in an MDT (66% rising to 87%; P=0.027), an increase in the rate of surgical resection (from 40% to 80%) and more patients being admitted electively (from 25% to 80%; P<0.001). There was a reduction in the median length of stay (8 days reduced to 4.5 days; P<0.001). For the cohort of GBM patients that went on to have chemoradiotherapy we improved median survival to 18 months, with 35% of patients alive at two years, comparable to international outcomes. Implementing a specialist neurosurgical oncology service begins with understanding the patient care pathway. Our patients have benefitted from the culture of subspecialisation and the excellent inter-disciplinary working

A new learning algorithm for a fully connected neuro-fuzzy inference system.

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Chen, C L Philip; Wang, Jing; Wang, Chi-Hsu; Chen, Long

2014-10-01

A traditional neuro-fuzzy system is transformed into an equivalent fully connected three layer neural network (NN), namely, the fully connected neuro-fuzzy inference systems (F-CONFIS). The F-CONFIS differs from traditional NNs by its dependent and repeated weights between input and hidden layers and can be considered as the variation of a kind of multilayer NN. Therefore, an efficient learning algorithm for the F-CONFIS to cope these repeated weights is derived. Furthermore, a dynamic learning rate is proposed for neuro-fuzzy systems via F-CONFIS where both premise (hidden) and consequent portions are considered. Several simulation results indicate that the proposed approach achieves much better accuracy and fast convergence.

libNeuroML and PyLEMS: using Python to combine procedural and declarative modeling approaches in computational neuroscience.

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Vella, Michael; Cannon, Robert C; Crook, Sharon; Davison, Andrew P; Ganapathy, Gautham; Robinson, Hugh P C; Silver, R Angus; Gleeson, Padraig

2014-01-01

NeuroML is an XML-based model description language, which provides a powerful common data format for defining and exchanging models of neurons and neuronal networks. In the latest version of NeuroML, the structure and behavior of ion channel, synapse, cell, and network model descriptions are based on underlying definitions provided in LEMS, a domain-independent language for expressing hierarchical mathematical models of physical entities. While declarative approaches for describing models have led to greater exchange of model elements among software tools in computational neuroscience, a frequent criticism of XML-based languages is that they are difficult to work with directly. Here we describe two Application Programming Interfaces (APIs) written in Python (http://www.python.org), which simplify the process of developing and modifying models expressed in NeuroML and LEMS. The libNeuroML API provides a Python object model with a direct mapping to all NeuroML concepts defined by the NeuroML Schema, which facilitates reading and writing the XML equivalents. In addition, it offers a memory-efficient, array-based internal representation, which is useful for handling large-scale connectomics data. The libNeuroML API also includes support for performing common operations that are required when working with NeuroML documents. Access to the LEMS data model is provided by the PyLEMS API, which provides a Python implementation of the LEMS language, including the ability to simulate most models expressed in LEMS. Together, libNeuroML and PyLEMS provide a comprehensive solution for interacting with NeuroML models in a Python environment.

libNeuroML and PyLEMS: using Python to combine imperative and declarative modelling approaches in computational neuroscience

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Michael eVella

2014-04-01

Full Text Available NeuroML is an XML-based model description language, which provides a powerful common data format for defining and exchanging models of neurons and neuronal networks. In the latest version of NeuroML, the structure and behavior of ion channel, synapse, cell,and network model descriptions are based on underlying definitions provided in LEMS, a domain-independent language for expressing hierarchical mathematical models of physical entities. While declarative approaches for describing models have led to greater exchange of model elements among software tools in computational neuroscience, a frequent criticism of XML-based languages is that they are difficult to work with directly. Here we describe two APIs (Application Programming Interfaces written in Python (http://www.python.org, which simplify the process of developing and modifying models expressed in NeuroML and LEMS. The libNeuroML API provides a Python object model with a direct mapping to all NeuroML concepts defined by the NeuroML Schema, which facilitates reading and writing the XML equivalents. In addition, it offers a memory-efficient, array-based internal representation, which is useful for handling large-scale connectomics data. The libNeuroML API also includes support for performing common operations that are required when working with NeuroML documents. Access to the LEMS data model is provided by the PyLEMS API, which provides a Python implementation of the LEMS language, including the ability to simulate most models expressed in LEMS. Together, libNeuroML and PyLEMS provide a comprehensive solution for interacting with NeuroML models in a Python environment.

Neuro fuzzy control of the FES assisted freely swinging leg of paraplegic subjects

NARCIS (Netherlands)

van der Spek, J.H.; Velthuis, W.J.R.; Veltink, Petrus H.; de Vries, Theodorus J.A.

1996-01-01

The authors designed a neuro fuzzy control strategy for control of cyclical leg movements of paraplegic subjects. The cyclical leg movements were specified by three `swing phase objectives', characteristic of natural human gait. The neuro fuzzy controller is a combination of a fuzzy logic controller

The neurogenic factor NeuroD1 is expressed in post-mitotic cells during juvenile and adult Xenopus neurogenesis and not in progenitor or radial glial cells.

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Laure Anne D'Amico

Full Text Available In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU or in situ hybridizations for cell type markers (Vimentin, Sox2. We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA- cells and not radial glial (Vimentin+ or progenitors (Sox2+ cells.

The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization.

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Frecska, Ede; Bokor, Petra; Winkelman, Michael

2016-01-01

Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor (Sig-1R) agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: (1) the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and (2) on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the Sig-1R which can explain its widespread therapeutic indications.

The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization

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Ede eFrecska

2016-03-01

Full Text Available Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: 1 the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and 2 on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the sigma-1 receptor which can explain its widespread therapeutic indications.

Adaptive neuro-fuzzy control of ionic polymer metal composite actuators

International Nuclear Information System (INIS)

Thinh, Nguyen Truong; Yang, Young-Soo; Oh, Il-Kwon

2009-01-01

An adaptive neuro-fuzzy controller was newly designed to overcome the degradation of the actuation performance of ionic polymer metal composite actuators that show highly nonlinear responses such as a straightening-back problem under a step excitation. An adaptive control algorithm with the merits of fuzzy logic and neural networks was applied for controlling the tip displacement of the ionic polymer metal composite actuators. The reference and actual displacements and the change of the error with the electrical inputs were recorded to generate the training data. These data were used for training the adaptive neuro-fuzzy controller to find the membership functions in the fuzzy control algorithm. Software simulation and real-time experiments were conducted by using the Simulink and dSPACE environments. Present results show that the current adaptive neuro-fuzzy controller can be successfully applied to the reliable control of the ionic polymer metal composite actuator for which the performance degrades under long-time actuation

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

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Asoka Banno

2018-01-01

Full Text Available Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.

Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

Science.gov (United States)

Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

2016-01-01

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

A wearable neuro-feedback system with EEG-based mental status monitoring and transcranial electrical stimulation.

Science.gov (United States)

Roh, Taehwan; Song, Kiseok; Cho, Hyunwoo; Shin, Dongjoo; Yoo, Hoi-Jun

2014-12-01

A wearable neuro-feedback system is proposed with a low-power neuro-feedback SoC (NFS), which supports mental status monitoring with encephalography (EEG) and transcranial electrical stimulation (tES) for neuro-modulation. Self-configured independent component analysis (ICA) is implemented to accelerate source separation at low power. Moreover, an embedded support vector machine (SVM) enables online source classification, configuring the ICA accelerator adaptively depending on the types of the decomposed components. Owing to the hardwired accelerating functions, the NFS dissipates only 4.45 mW to yield 16 independent components. For non-invasive neuro-modulation, tES stimulation up to 2 mA is implemented on the SoC. The NFS is fabricated in 130-nm CMOS technology.

Brainstem auditory evoked potential monitoring and neuro-endoscopy: Two tools to ensure hearing preservation and surgical success during microvascular decompression

Directory of Open Access Journals (Sweden)

Cheng-Chia Lee

2014-06-01

Conclusion: The results of this retrospective study emphasized the importance of BAEP monitoring and neuro-endoscopy during MVD. It is well known that BAEP monitoring can preserve hearing function, and the endoscope offers neurosurgeons a second look to identify the nerve root entry zone and confirms the position of the Teflon felt. These two tools are especially useful in difficult cases.

Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

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Nien Yee Kow

2013-01-01

Full Text Available System lupus erythematosus (SLE is an immune-complex-mediated autoimmune condition with protean immunological and clinical manifestation. While SLE has classically been advocated as a B-cell or T-cell disease, it is unlikely that a particular cell type is more pathologically predominant than the others. Indeed, SLE is characterized by an orchestrated interplay amongst different types of immunopathologically important cells participating in both innate and adaptive immunity including the dendritic cells, macrophages, neutrophils and lymphocytes, as well as traditional nonimmune cells such as endothelial, epithelial, and renal tubular cells. Amongst the antigen-presenting cells and lymphocytes, and between lymphocytes, the costimulatory pathways which involve mutual exchange of information and signalling play an essential role in initiating, perpetuating, and, eventually, attenuating the proinflammatory immune response. In this review, advances in the knowledge of established costimulatory pathways such as CD28/CTLA-4-CD80/86, ICOS-B7RP1, CD70-CD27, OX40-OX40L, and CD137-CD137L as well as their potential roles involved in the pathophysiology of SLE will be discussed. Attempts to target these costimulatory pathways therapeutically will pave more potential treatment avenues for patients with SLE. Preliminary laboratory and clinical evidence of the potential therapeutic value of manipulating these costimulatory pathways in SLE will also be discussed in this review.

Virtual reality exposure and neuro-bio feedback to help coping with traumatic events

NARCIS (Netherlands)

Neerincx, M.A.; Kallen, V.L.; Brouwer, A.-M.; Leer, L. van der; Brinke, M. ten

2010-01-01

Recent research shows that Virtual Reality (VR) exposure or bio-neuro feedback can help professionals to cope with possibly traumatic events. This paper presents a neuro-bio VR system that combines both methods in order to further improve the prevention and therapy of trauma-related disorders. This

New concept of direct torque neuro-fuzzy control for induction motor drives. Simulation study

Energy Technology Data Exchange (ETDEWEB)

Grabowski, P.Z. [Institute of Control and Industrial Electronics, Warsaw University of Technology, Warsaw (Poland)

1997-12-31

This paper presents a new control strategy in the discrete Direct Torque Control (DTC) based on neuro-fuzzy structure. Two schemes are proposed: neuro-fuzzy switching times calculator and neuro-fuzzy incremental controller with space vector modulator. These control strategies guarantee very good dynamic and steady-states characteristics, with very low sampling time and constant switching frequency. The proposed techniques are verified by simulation study of the whole drive system and results are compared with conventional discrete Direct Torque Control method. (orig.) 18 refs.

Immunotherapy Response Assessment in Neuro-Oncology (iRANO): A Report of the RANO Working Group

Science.gov (United States)

Okada, Hideho; Weller, Michael; Huang, Raymond; Finocchiaro, Gaetano; Gilbert, Mark R.; Wick, Wolfgang; Ellingson, Benjamin M.; Hashimoto, Naoya; Pollack, Ian F.; Brandes, Alba A.; Franceschi, Enrico; Herold-Mende, Christel; Nayak, Lakshmi; Panigrahy, Ashok; Pope, Whitney B.; Prins, Robert; Sampson, John H.; Wen, Patrick Y.; Reardon, David A.

2015-01-01

Immunotherapy represents a promising area of therapy among neuro-oncology patients. However, early phase studies reveal unique challenges associated with assessment of radiological changes reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumor regression, can still occur following initial apparent progression or appearance of new lesions. Refinement of response assessment criteria for neuro-oncology patients undergoing immunotherapy is therefore warranted. A multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describes immunotherapy response assessment for neuro-oncology (iRANO) criteria that are based on guidance for determination of tumor progression outlined by the immune-related response criteria (irRC) and the response assessment in neuro-oncology (RANO) working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease (PD) within six months of initiating immunotherapy including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for use of corticosteroids. The role of advanced imaging techniques and measurement of clinical benefit endpoints including neurologic and immunologic functions are reviewed. The iRANO guidelines put forth herein will evolve successively to improve their utility as further experience from immunotherapy trials in neuro-oncology accumulate. PMID:26545842

Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease?

Science.gov (United States)

Deming, Yuetiva; Li, Zeran; Benitez, Bruno A; Cruchaga, Carlos

2018-06-20

There are currently no effective therapeutics for Alzheimer disease (AD). Clinical trials targeting amyloid beta thus far have shown very little benefit and only in the earliest stages of disease. These limitations have driven research to identify alternative therapeutic targets, one of the most promising is the triggering receptor expressed on myeloid cells 2 (TREM2). Areas covered: Here, we review the literature to-date and discuss the potentials and pitfalls for targeting TREM2 as a potential therapeutic for AD. We focus on research in animal and cell models for AD and central nervous system injury models which may help in understanding the role of TREM2 in disease. Expert opinion: Studies suggest TREM2 plays a key role in AD pathology; however, results have been conflicting about whether TREM2 is beneficial or harmful. More research is necessary before designing TREM2-targeting therapies. Successful therapeutics will most likely be administered early in disease.

Realizing the therapeutic potential of rare earth elements in designing nanoparticles to target and treat glioblastoma.

Science.gov (United States)

Lu, Victor M; McDonald, Kerrie L; Townley, Helen E

2017-10-01

The prognosis of brain cancer glioblastoma (GBM) is poor, and despite intense research, there have been no significant improvements within the last decade. This stasis implicates the need for more novel therapeutic investigation. One such option is the use of nanoparticles (NPs), which can be beneficial due to their ability to penetrate the brain, overcome the blood-brain barrier and take advantage of the enhanced permeation and retention effect of GBM to improve specificity. Rare earth elements possess a number of interesting natural properties due to their unique electronic configuration, which may prove therapeutically advantageous in an NP formulation. The underexplored exciting potential for rare earth elements to augment the therapeutic potential of NPs in GBM treatment is discussed in this review.

A Neuro-Fuzzy Approach in the Classification of Students’ Academic Performance

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Quang Hung Do

2013-01-01

Full Text Available Classifying the student academic performance with high accuracy facilitates admission decisions and enhances educational services at educational institutions. The purpose of this paper is to present a neuro-fuzzy approach for classifying students into different groups. The neuro-fuzzy classifier used previous exam results and other related factors as input variables and labeled students based on their expected academic performance. The results showed that the proposed approach achieved a high accuracy. The results were also compared with those obtained from other well-known classification approaches, including support vector machine, Naive Bayes, neural network, and decision tree approaches. The comparative analysis indicated that the neuro-fuzzy approach performed better than the others. It is expected that this work may be used to support student admission procedures and to strengthen the services of educational institutions.

Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

Science.gov (United States)

Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

2006-01-01

Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA) administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene. PMID:16638118

Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

Directory of Open Access Journals (Sweden)

Castellano Bernardo

2006-04-01

Full Text Available Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene.

NeuroVR: an open source virtual reality platform for clinical psychology and behavioral neurosciences.

Science.gov (United States)

Riva, Giuseppe; Gaggioli, Andrea; Villani, Daniela; Preziosa, Alessandra; Morganti, Francesca; Corsi, Riccardo; Faletti, Gianluca; Vezzadini, Luca

2007-01-01

In the past decade, the use of virtual reality for clinical and research applications has become more widespread. However, the diffusion of this approach is still limited by three main issues: poor usability, lack of technical expertise among clinical professionals, and high costs. To address these challenges, we introduce NeuroVR (http://www.neurovr.org--http://www.neurotiv.org), a cost-free virtual reality platform based on open-source software, that allows non-expert users to adapt the content of a pre-designed virtual environment to meet the specific needs of the clinical or experimental setting. Using the NeuroVR Editor, the user can choose the appropriate psychological stimuli/stressors from a database of objects (both 2D and 3D) and videos, and easily place them into the virtual environment. The edited scene can then be visualized in the NeuroVR Player using either immersive or non-immersive displays. Currently, the NeuroVR library includes different virtual scenes (apartment, office, square, supermarket, park, classroom, etc.), covering two of the most studied clinical applications of VR: specific phobias and eating disorders. The NeuroVR Editor is based on Blender (http://www.blender.org), the open source, cross-platform suite of tools for 3D creation, and is available as a completely free resource. An interesting feature of the NeuroVR Editor is the possibility to add new objects to the database. This feature allows the therapist to enhance the patient's feeling of familiarity and intimacy with the virtual scene, i.e., by using photos or movies of objects/people that are part of the patient's daily life, thereby improving the efficacy of the exposure. The NeuroVR platform runs on standard personal computers with Microsoft Windows; the only requirement for the hardware is related to the graphics card, which must support OpenGL.

Angiographic assessment of atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy.

Science.gov (United States)

Çildağ, Mehmet B; Ertuğrul, Bülent M; Köseoğlu, Ömer Fk; Çildağ, Songül; Armstrong, David G

2018-06-01

The aim of this study was to investigate atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy and compare them with patients with diabetic foot without charcot neuro-arthropathy. This retrospective study consists of 78 patients with diabetic foot who had lower extremity angiography with antegrade approach. All patients were classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the side of diabetic foot was determined by using the Bollinger angiogram scoring method. Comparison of atherosclerotic load between the two groups was performed. The mean of total and infrapopliteal level angiogram scoring of all patients was 33.3 (standard deviation, sd:±17.2) and 29.3 (sd:±15.6), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:±11.6) and 15.7 (sd:±10.4), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group was 42.8 (sd:±12.7) and 37.7 (sd:±12.0), respectively. There was a statistically significant difference between the two groups of mean total and infrapopliteal angiogram scoring (p diabetic foot and chronic charcot neuro-arthropathy is significantly less than in patients with neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy. Copyright © 2017. Published by Elsevier Taiwan LLC.

Functional Neuro-Imaging and Post-Traumatic Olfactory Impairment

Science.gov (United States)

Roberts, Richard J.; Sheehan, William; Thurber, Steven; Roberts, Mary Ann

2010-01-01

Objective: To evaluate via a research literature survey the anterior neurological significance of decreased olfactory functioning following traumatic brain injuries. Materials and Methods: A computer literature review was performed to locate all functional neuro-imaging studies on patients with post-traumatic anosmia and other olfactory deficits. Results: A convergence of findings from nine functional neuro-imaging studies indicating evidence for reduced metabolic activity at rest or relative hypo-perfusion during olfactory activations. Hypo-activation of the prefrontal regions was apparent in all nine post-traumatic samples, with three samples yielding evidence of reduced activity in the temporal regions as well. Conclusions: The practical ramifications include the reasonable hypothesis that a total anosmic head trauma patient likely has frontal lobe involvement. PMID:21716782

In-stream attenuation of neuro-active pharmaceuticals and their metabolites

Science.gov (United States)

Writer, Jeffrey; Antweiler, Ronald C.; Ferrar, Imma; Ryan, Joseph N.; Thurman, Michael

2013-01-01

In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

Aspects of pericytes and their potential therapeutic use

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Justyna Różycka

2017-03-01

Full Text Available Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2, β-type platelet-derived growth factor receptor (PDGFRβ, smooth muscle α-actin (α-SMA, regulator of G protein signalling 5 (RGS5, the adhesion protein CD146 and nestin. Different functions in physiological processes are assigned to pericytes such as maintaining the integrity and senescence of endothelial cells, transregulation of vascular tone or the potential to differentiate into other cells. Probably they are also involved in pathological processes such as tissues fibrosis. In this review, we focus on the participation of pericytes in the process of blood vessel formation, the regeneration of skeletal muscle tissue and fibrosis. Strong evidence for pericytes’ participation in endothelial homeostasis, as well as in pathological conditions such as fibrosis, reveals a broad potential for the therapeutic use of these cells. Targeted pharmacological modulation of pericytes, leading to blocking signalling pathways responsible for the differentiation of pericytes into myofibroblasts, seems to be a promising strategy for the treatment of fibrosis in the early stages.

Aspects of pericytes and their potential therapeutic use.

Science.gov (United States)

Różycka, Justyna; Brzóska, Edyta; Skirecki, Tomasz

2017-03-13

Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2), β-type platelet-derived growth factor receptor (PDGFRβ), smooth muscle α-actin (α-SMA), regulator of G protein signalling 5 (RGS5), the adhesion protein CD146 and nestin. Different functions in physiological processes are assigned to pericytes such as maintaining the integrity and senescence of endothelial cells, transregulation of vascular tone or the potential to differentiate into other cells. Probably they are also involved in pathological processes such as tissues fibrosis. In this review, we focus on the participation of pericytes in the process of blood vessel formation, the regeneration of skeletal muscle tissue and fibrosis. Strong evidence for pericytes' participation in endothelial homeostasis, as well as in pathological conditions such as fibrosis, reveals a broad potential for the therapeutic use of these cells. Targeted pharmacological modulation of pericytes, leading to blocking signalling pathways responsible for the differentiation of pericytes into myofibroblasts, seems to be a promising strategy for the treatment of fibrosis in the early stages.

Molecular Pathology of Neuro-AIDS (CNS-HIV

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Eliezer Masliah

2009-03-01

Full Text Available The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuro-inflammatory condition known as HIV encephalitis (HIVE. With the advent of more effective anti-retroviral therapies, HIVE has shifted from a sub-acute to a chronic condition. The neurodegenerative process in patients with HIVE is characterized by synaptic and dendritic damage to pyramidal neurons, loss of calbindin-immunoreactive interneurons and myelin loss. The mechanisms leading to neurodegeneration in HIVE might involve a variety of pathways, and several lines of investigation have found that interference with signaling factors mediating neuroprotection might play an important role. These signaling pathways include, among others, the GSK3b, CDK5, ERK, Pyk2, p38 and JNK cascades. Of these, GSK3b has been a primary focus of many previous studies showing that in infected patients, HIV proteins and neurotoxins secreted by immune-activated cells in the brain abnormally activate this pathway, which is otherwise regulated by growth factors such as FGF. Interestingly, modulation of the GSK3b signaling pathway by FGF1 or GSK3b inhibitors (lithium, valproic acid is protective against HIV neurotoxicity, and several pilot clinical trials have demonstrated cognitive improvements in HIV patients treated with GSK3b inhibitors. In addition to the GSK3b pathway, the CDK5 pathway has recently been implicated as a mediator of neurotoxicity in HIV, and HIV proteins might activate this pathway and subsequently disrupt the diverse processes that CDK5 regulates, including synapse formation and plasticity and neurogenesis. Taken together, the GSK3b and CDK5 signaling pathways are important regulators of neurotoxicity in HIV, and modulation of these factors might have therapeutic potential in the treatment of patients suffering from HIVE. In this context, the subsequent sections will focus on reviewing the

Altered blood-brain barrier transport in neuro-inflammatory disorders.

Science.gov (United States)

Schenk, Geert J; de Vries, Helga E

2016-06-01

During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specific transport and non-specific transport pathways. Potential alterations in transport routes like adsorptive mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. In contrast, the delivery of (targeted) drugs could be hampered during inflammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-inflammatory status of the neurovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this review we will briefly discuss how the function of the BBB can be affected during disease and how this may influence the delivery of drugs into the diseased CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early evolution and recovery from excitotoxic injury in the neonatal rat brain

NARCIS (Netherlands)

Lookeren Campagne, van M.; Verheul, H.B.; Nicolaij, K.; Balázs, R.E.

1994-01-01

We explored the therapeutic potentials of two N-methyl-D-aspartate (NMDA) receptor antagonists in vivo using different techniques. NMDA injected into the striatum of neonatal rats (20 nmol/0.5 microliters) induced a rapid increase in the diffusion-weighted (DW) image intensity, spreading over a

Neuro-inspired computing using resistive synaptic devices

CERN Document Server

2017-01-01

This book summarizes the recent breakthroughs in hardware implementation of neuro-inspired computing using resistive synaptic devices. The authors describe how two-terminal solid-state resistive memories can emulate synaptic weights in a neural network. Readers will benefit from state-of-the-art summaries of resistive synaptic devices, from the individual cell characteristics to the large-scale array integration. This book also discusses peripheral neuron circuits design challenges and design strategies. Finally, the authors describe the impact of device non-ideal properties (e.g. noise, variation, yield) and their impact on the learning performance at the system-level, using a device-algorithm co-design methodology. • Provides single-source reference to recent breakthroughs in resistive synaptic devices, not only at individual cell-level, but also at integrated array-level; • Includes detailed discussion of the peripheral circuits and array architecture design of the neuro-crossbar system; • Focuses on...

Revisiting nicotine's role in the ageing brain and cognitive impairment

DEFF Research Database (Denmark)

Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

2017-01-01

stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening...... in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

Science.gov (United States)

Fetterman, James W; Zdanowicz, Martin M

2009-07-01

The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.

Synergistic nuclear import of NeuroD1 and its partner transcription factor, E47, via heterodimerization

International Nuclear Information System (INIS)

Mehmood, Rashid; Yasuhara, Noriko; Oe, Souichi; Nagai, Masahiro; Yoneda, Yoshihiro

2009-01-01

The transition from undifferentiated pluripotent cells to terminally differentiated neurons is coordinated by a repertoire of transcription factors. NeuroD1 is a type II basic helix loop helix (bHLH) transcription factor that plays critical roles in neuronal differentiation and maintenance in the central nervous system. Its dimerization with E47, a type I bHLH transcription factor, leads to the transcriptional regulation of target genes. Mounting evidence suggests that regulating the localization of transcription factors contributes to the regulation of their activity during development as defects in their localization underlie a variety of developmental disorders. In this study, we attempted to understand the nuclear import mannerisms of NeuroD1 and E47. We found that the nuclear import of NeuroD1 and E47 is energy-dependent and involves the Ran-mediated pathway. Herein, we demonstrate that NeuroD1 and E47 can dimerize inside the cytoplasm before their nuclear import. Moreover, this dimerization promotes nuclear import as the nuclear accumulation of NeuroD1 was enhanced in the presence of E47 in an in vitro nuclear import assay, and NLS-deficient NeuroD1 was successfully imported into the nucleus upon E47 overexpression. NeuroD1 also had a similar effect on the nuclear accumulation of NLS-deficient E47. These findings suggest a novel role for dimerization that may promote, at least partially, the nuclear import of transcription factors allowing them to function efficiently in the nucleus.

Potential Therapeutic Benefits of Green and Fermented Rooibos (Aspalathus linearis) in Dermal Wound Healing.

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Pringle, Nadine A; Koekemoer, Trevor C; Holzer, Andrea; Young, Carly; Venables, Luanne; van de Venter, Maryna

2018-02-28

The process of wound healing constitutes an ordered sequence of events that provides numerous opportunities for therapeutic intervention to improve wound repair. Rooibos, Aspalathus linearis , is a popular ingredient in skin care products, however, little scientific data exists exploring its therapeutic potential. In the present study, we evaluated the effects of fermented and aspalathin-enriched green rooibos in various in vitro models representative of dermal wound healing. Treatment of RAW 264.7 macrophages with fermented rooibos resulted in increased nitric oxide production as well as increased levels of cellular inducible nitric oxide synthase and cyclooxygenase-2, which are typical markers for classically activated macrophages. In contrast, the green extract was devoid of such activity. Using glycated gelatin as a model to mimic diabetic wounds, only the green extract showed potential to reduce cyclooxygenase-2 levels. Considering the role of reactive oxygen species in wound healing, the effects of rooibos on oxidative stress and cell death in human dermal fibroblasts was evaluated. Both fermented and green rooibos decreased cellular reactive oxygen species and attenuated apoptotic/necrotic cell death. Our findings highlight several properties that support the therapeutic potential of rooibos, and demonstrate that green and fermented rooibos present distinctly different properties with regards to their application in wound healing. The proinflammatory nature of fermented rooibos may have therapeutic value for wounds characterised with a delayed initial inflammatory phase, such as early diabetic wounds. The green extract is more suited to wounds burdened with excessive inflammation as it attenuated cyclooxygenase-2 levels and effectively protected fibroblasts against oxidative stress. Georg Thieme Verlag KG Stuttgart · New York.

Micro-angiography for neuro-vascular imaging. I. Experimental evaluation and feasibility

International Nuclear Information System (INIS)

Ganguly, Arundhuti; Rudin, Stephen; Bednarek, Daniel R.; Hoffmann, Kenneth R.; Kyprianou, Iacovos S.

2003-01-01

Minimally invasive image-guided neuro-vascular interventions require very high image-resolution and quality, specifically over regions-of-interest (ROI) crucial to the procedure. ROI imaging or micro-angiography, allows limited patient integral radiation dose while permitting rapid frame transfer of high-resolution images. The design and performance of a charge coupled device (CCD) based x-ray detector or micro-angiographic camera was assessed for neuro-vascular procedures. The detector consists of a 250-μm-thick CsI(Tl) phosphor fiber-optically coupled through a 1.8:1 taper to a CCD chip, with an effective image pixel size of 50 μm and a frame rate of 5 fps in the 2:1 pixel-binned mode. The characteristics of the camera including the modulation transfer function (MTF), the noise equivalent quanta, the detective quantum efficiency, observer studies, and the effect of geometric magnification were evaluated. The MTF was found to have nonzero (1.7%) value at the Nyquist frequency of 10 cycles/mm, while the DQE(0) had a value of ∼55%. All values were measured using head equivalent attenuating material in the beam at 80 kVp. Human observer studies performed using the 2 Alternative Forced Choice method revealed that iodinated vessels with inner diameter of 100 μm and 2 cm in length can be seen with a confidence level greater than 75%. The observer studies included a comparison with ideal observer performance calculations based on the integral signal to noise ratio in the image. Probabilities of visualization of various objects of interest in a neuro-intervention, such as stents, were assessed. A geometric magnification of 1 was found to be best for imaging under neuro-angiographic conditions. The detector appeared to satisfy all the demands of neuro-angiography and showed promise as an improvement over existing angiographic detectors

Therapeutic hypothermia for neonatal encephalopathy: a UK survey of opinion, practice and neuro-investigation at the end of 2007.

Science.gov (United States)

Kapetanakis, Andrew; Azzopardi, Denis; Wyatt, John; Robertson, Nicola J

2009-04-01

The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited. To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia. A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007. One hundred and twenty-five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective - similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia. In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty-five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up.

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

Science.gov (United States)

Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

2018-05-17

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

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Fabliha Ahmed Chowdhury

2018-01-01

Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents

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Da Hye Kim

2017-06-01

Full Text Available The therapeutic properties of Epimedium koreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer’s disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B and α-glucosidase. The results show that icaritin and icariside II exhibit potent inhibitory activities, with 50% inhibition concentration (IC50 values of 11.59 ± 1.39 μM and 9.94 ± 0.15 μM against PTP1B and 74.42 ± 0.01 and 106.59 ± 0.44 μM against α-glucosidase, respectively. With the exceptions of icaritin and icariside II, glycosylated flavonoids did not exhibit any inhibitory effects in the two assays. Enzyme kinetics analyses revealed that icaritin and icariside II demonstrated noncompetitive-type inhibition against PTP1B, with inhibition constant (Ki values of 11.41 and 11.66 μM, respectively. Moreover, molecular docking analysis confirmed that icaritin and icariside II both occupy the same site as allosteric ligand. Thus, the molecular docking simulation results were in close agreement with the experimental data with respect to inhibition activity. In conclusion, deglycosylated metabolites of icariin from E. koreanum might offer therapeutic potential for the treatment of type 2 diabetes mellitus.

Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

OpenAIRE

Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

2006-01-01

Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn S...

[Music in health promotion and therapeutic practice. Cultural, theoretical and clinical perspectives.

Science.gov (United States)

Mastnak, Wolfgang

2016-12-01

Music can serve as a shelter and music therapy can provide spaces for symbolic experience and the modification of behavioural and cognitive patterns. Explaining the power of music, ancient theories speak of an analogy between music and man. Similar views are also found in modern music therapy such as Sound Work, a voice-body-based model. Complementary to the aspect of analogy, the principle of transformation is of vital importance, such as the transitions between the five elements, the solid organs and the pentatonic scale in Chinese music therapy, for instance. Distinct modes of matter-mind-transitions define the theoretical framework of neuro-psychologically based music therapy. A triadic model encompassing neuro-endocrine, psychological and aesthetic facets explains the preventive and therapeutic effect of music in stress-associated disorders and burnout. Finally, a new voice-based model (Arion Psychovocal Therapy) is presented. Integrating anthropological theories, anatomical perspectives of movement, and artistic features it focuses on psychiatry, psycho-prevention, and public health and highlights the interdisciplinary nature of music in medicine. © Georg Thieme Verlag KG Stuttgart · New York.

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

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Irina Gavrilovskaya

2012-01-01

Full Text Available American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS. Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Autonomous CaMKII Activity as a Drug Target for Histological and Functional Neuroprotection after Resuscitation from Cardiac Arrest

Directory of Open Access Journals (Sweden)

Guiying Deng

2017-01-01

Full Text Available The Ca2+/calmodulin-dependent protein kinase II (CaMKII is a major mediator of physiological glutamate signaling, but its role in pathological glutamate signaling (excitotoxicity remains less clear, with indications for both neuro-toxic and neuro-protective functions. Here, the role of CaMKII in ischemic injury is assessed utilizing our mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR. CaMKII inhibition (with tatCN21 or tatCN19o at clinically relevant time points (30 min after resuscitation greatly reduces neuronal injury. Importantly, CaMKII inhibition also works in combination with mild hypothermia, the current standard of care. The relevant drug target is specifically Ca2+-independent “autonomous” CaMKII activity generated by T286 autophosphorylation, as indicated by substantial reduction in injury in autonomy-incompetent T286A mutant mice. In addition to reducing cell death, tatCN19o also protects the surviving neurons from functional plasticity impairments and prevents behavioral learning deficits, even at extremely low doses (0.01 mg/kg, further highlighting the clinical potential of our findings.

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

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Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

2015-12-01

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

PENERAPAN HIPNOTEACHING MELALUI NEURO-LINGUISTIC PROGRAMMING DALAM PEMBELAJARAN KIMIA

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S. Ismuzaroh

2013-10-01

Full Text Available Tujuan penerapan hypnoteaching melalui neuro linguistic programming (NLP dalam proses pembelajaran kimia adalah untuk menghilangkan pikiran negatif siswa terhadap pembelajaran kimia, yang selanjutnya meningkatkan minat, motivasi dan keaktifan belajar kimia siswa. Hasil penelitian menunjukkan siswa lebih terbuka, berani mengemukakan pendapat terhadap permasalahan kimia yang pelajari, siswa merasa fresh, dan nyaman. Hypnoteaching goals through the application of neuro linguistic programming (NLP is a chemical in the learning process to eliminate the negative thoughts of students towards learning chemistry, which further increase the interest, motivation and active learning chemistry students. Results showed students were more open, daring to express opinions on issues studied chemistry, students feel fresh, and comfortable.

Role of imaging in the management of neuro-ophthalmic disorders

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Gandhi Rashmin

2011-01-01

Full Text Available Advancements in physics, computers, and imaging science in the last century have seen neuro-imaging evolving from a plain X-ray to computed tomography, magnetic resonance imaging scans, noninvasive angiography, and special sequences such as fat suppression, fluid attenuation recovery and diffusion-weighted imaging. A prompt prescription of an appropriate imaging modality and the most suitable sequence can increase the diagnostic yield, and in many instances, it can be a sight-saving and even a life-saving decision. This article discusses basic principles of neuro-imaging, its common indications, and the appropriate application in an ophthalmology practice.

Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

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Ying-Zheng Zhao

Full Text Available Intranasal administration of phospholipid-based gelatin nanoparticles (GNP was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP on hemiparkinsonian rats.The SP-loaded gelatin nanoparticles (SP-GNP were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM. The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH, phosphorylated c-Jun protein (p-c-Jun and Caspase-3 (Cas-3 expressed in substantia nigra (SN region of hemiparkinsonian rats.PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

Therapeutic potential of Aegle marmelos (L.-An overview

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Shahedur Rahman

2014-02-01

Full Text Available Medicinal plants are used in herbalism. They form the easily available source for healthcare purposes in rural and tribal areas. In the present review, an attempt has been made to congregate the phytochemical and pharmacological studies done on an important medicinal plant Aegle marmelos. Extensive experimental and clinical studies prove that Aegle marmelos possesses antidiarrhoeal, antimicrobial, antiviral, radioprotective, anticancer, chemopreventive, antipyretic, ulcer healing, antigenotoxic, diuretic, antifertility and anti-inflammatory properties, which help it to play role in prevention and treatment of many disease. Therefore, it is worthwhile to review its therapeutic properties to give an overview of its status to scientist both modern and ancient. This review also encompasses on the potential application of the above plant in the pharmaceutical field due to its wide pharmacological activities.

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

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Umberto Tosi

2017-02-01

Full Text Available Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

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Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells

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2012-01-01

Background Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved. Results Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H2O2) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H2O2. Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H2O2-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H2O2-treated cells. Conclusions In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells. PMID:23227925

Characterization and modeling of a new magnetorheological damper with meandering type valve using neuro-fuzzy

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Fitrian Imaduddin

2017-10-01

Full Text Available This paper presents the characterization and hysteresis modeling of magnetorheological (MR damper with meandering type valve. The meandering type MR valve, which employs the combination of multiple annular and radial flow passages, has been introduced as the new type of high performance MR valve with higher achievable pressure drop and controllable performance range than similar counterparts in its class. Since the performance of a damper is highly determined by the valve performance, the utilization of the meandering type MR valve in an MR damper could potentially improve the damper performance. The damping force characterization of the MR damper is conducted by measuring the damping force as a response to the variety of harmonic excitations. The hysteresis behavior of the damper is identified by plotting the damping force relationship to the excitation displacement and velocity. For the hysteresis modeling purpose, some parts of the data are taken as the training data source for the optimization parameters in the neuro-fuzzy model. The performance of the trained neuro-fuzzy model is assessed by validating the model output with the remaining measurement data and benchmarking the results with the output of the parametric hysteresis model. The validation results show that the neuro-fuzzy model is demonstrating good agreement with the measurement results indicated by the average relative error of only around 7%. The model also shows robustness with no tendency of growing error when the input values are changed.

Commercially available interactive video games in burn rehabilitation: therapeutic potential.

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Parry, Ingrid S; Bagley, Anita; Kawada, Jason; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

2012-06-01

Commercially available interactive video games (IVG) like the Nintendo Wii™ (NW) and PlayStation™II Eye Toy (PE) are increasingly used in the rehabilitation of patients with burn. Such games have gained popularity in burn rehabilitation because they encourage range of motion (ROM) while distracting from pain. However, IVGs were not originally designed for rehabilitation purposes but rather for entertainment and may lack specificity for achieving rehabilitative goals. Objectively evaluating the specific demands of IVGs in relation to common burn therapy goals will determine their true therapeutic benefit and guide their use in burn rehabilitation. Upper extremity (UE) motion of 24 normal children was measured using 3D motion analysis during play with the two types of IVGs most commonly described for use after burn: NW and PE. Data was analyzed using t-tests and One-way Analysis of Variance. Active range of motion for shoulder flexion and abduction during play with both PE and NW was within functional range, thus supporting the idea that IVGs offer activities with therapeutic potential to improve ROM. PE resulted in higher demands and longer duration of UE motion than NW, and therefore may be the preferred tool when UE ROM or muscular endurance are the goals of rehabilitation. When choosing a suitable IVG for application in rehabilitation, the user's impairment together with the therapeutic attributes of the IVG should be considered to optimize outcome. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles

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Bin Zhang

2016-02-01

Full Text Available The intense research focus on stem and progenitor cells could be attributed to their differentiation potential to generate new cells to replace diseased or lost cells in many highly intractable degenerative diseases, such as Alzheimer disease, multiple sclerosis, and heart diseases. However, experimental and clinical studies have increasingly attributed the therapeutic efficacy of these cells to their secretion. While stem and progenitor cells secreted many therapeutic molecules, none of these molecules singly or in combination could recapitulate the functional effects of stem cell transplantations. Recently, it was reported that extracellular vesicles (EVs could recapitulate the therapeutic effects of stem cell transplantation. Based on the observations reported thus far, the prevailing hypothesis is that stem cell EVs exert their therapeutic effects by transferring biologically active molecules such as proteins, lipids, mRNA, and microRNA from the stem cells to injured or diseased cells. In this respect, stem cell EVs are similar to EVs from other cell types. They are both primarily vehicles for intercellular communication. Therefore, the differentiating factor is likely due to the composition of their cargo. The cargo of EVs from different cell types are known to include a common set of proteins and also proteins that reflect the cell source of the EVs and the physiological or pathological state of the cell source. Hence, elucidation of the stem cell EV cargo would provide an insight into the multiple physiological or biochemical changes necessary to affect the many reported stem cell-based therapeutic outcomes in a variety of experimental models and clinical trials.

A neuro-fuzzy inference system for sensor failure detection using wavelet denoising, PCA and SPRT

International Nuclear Information System (INIS)

Na, Man Gyun

2001-01-01

In this work, a neuro-fuzzy inference system combined with the wavelet denoising, PCA(principal component analysis) and SPRT (sequential probability ratio test) methods is developed to detect the relevant sensor failure using other sensor signals. The wavelet denoising technique is applied to remove noise components in input signals into the neuro-fuzzy system. The PCA is used to reduce the dimension of an input space without losing a significant amount of information, The PCA makes easy the selection of the input signals into the neuro-fuzzy system. Also, a lower dimensional input space usually reduces the time necessary to train a neuro-fuzzy system. The parameters of the neuro-fuzzy inference system which estimates the relevant sensor signal are optimized by a genetic algorithm and a least-squares algorithm. The residuals between the estimated signals and the measured signals are used to detect whether the sensors are failed or not. The SPRT is used in this failure detection algorithm. The proposed sensor-monitoring algorithm was verified through applications to the pressurizer water level and the hot-leg flowrate sensors in pressurized water reactors

Citation classics in neuro-oncology: assessment of historical trends and scientific progress.

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Hachem, Laureen D; Mansouri, Alireza; Juraschka, Kyle; Taslimi, Shervin; Pirouzmand, Farhad; Zadeh, Gelareh

2017-09-01

Citation classics represent the highest cited works in a field and are often regarded as the most influential literature. Analyzing thematic trends in citation classics across eras enables recognition of important historical advances within a field. We present the first analysis of the citation classics in neuro-oncology. The Web of Science database was searched using terms relevant to "neuro-oncology." Articles with >400 citations were identified and the top 100 cited articles were evaluated. The top 100 neuro-oncology citation classics consisted of 43 clinical studies (17 retrospective, 10 prospective, 16 randomized trials), 43 laboratory investigations, 8 reviews/meta-analyses, and 6 guidelines/consensus statements. Articles were classified into 4 themes: 13 pertained to tumor classification, 37 to tumor pathogenesis/clinical presentation, 6 to imaging, 44 to therapy (15 chemotherapy, 10 radiotherapy, 5 surgery, 14 new agents). Gliomas were the most common tumor type examined, with 70 articles. There was a significant increase in the number of citation classics in the late 1990s, which was paralleled by an increase in studies examining tumor pathogenesis, chemotherapy, and new agents along with laboratory and randomized studies. The majority of citation classics in neuro-oncology are related to gliomas and pertain to tumor pathogenesis and treatment. The rise in citation classics in recent years investigating tumor biology, new treatment agents, and chemotherapeutics may reflect increasing scientific interest in nonsurgical treatments for CNS tumors and the need for fundamental investigations into disease processes. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

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Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

2015-11-01

Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

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Schepetkin, Igor A; Quinn, Mark T

2006-03-01

Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology.

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Eekers, Daniëlle Bp; In 't Ven, Lieke; Roelofs, Erik; Postma, Alida; Alapetite, Claire; Burnet, Neil G; Calugaru, Valentin; Compter, Inge; Coremans, Ida E M; Høyer, Morton; Lambrecht, Maarten; Nyström, Petra Witt; Romero, Alejandra Méndez; Paulsen, Frank; Perpar, Ana; de Ruysscher, Dirk; Renard, Laurette; Timmermann, Beate; Vitek, Pavel; Weber, Damien C; van der Weide, Hiske L; Whitfield, Gillian A; Wiggenraad, Ruud; Troost, Esther G C

2018-03-13

To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging. CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at www.cancerdata.org and will be updated whenever required. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Neuro-fuzzy models for systems identification applied to the operation of nuclear power plants

International Nuclear Information System (INIS)

Alves, Antonio Carlos Pinto Dias

2000-09-01

A nuclear power plant has a myriad of complex system and sub-systems that, working cooperatively, make the control of the whole plant. Nevertheless their operation be automatic most of the time, the integral understanding of their internal- logic can be away of the comprehension of even experienced operators because of the poor interpretability those controls offer. This difficulty does not happens only in nuclear power plants but in almost every a little more complex control system. Neuro-fuzzy models have been used for the last years in a attempt of suppress these difficulties because of their ability of modelling in linguist form even a system which behavior is extremely complex. This is a very intuitive human form of interpretation and neuro-fuzzy model are gathering increasing acceptance. Unfortunately, neuro-fuzzy models can grow up to become of hard interpretation because of the complexity of the systems under modelling. In general, that growing occurs in function of redundant rules or rules that cover a very little domain of the problem. This work presents an identification method for neuro-fuzzy models that not only allows models grow in function of the existent complexity but that beforehand they try to self-adapt to avoid the inclusion of new rules. This form of construction allowed to arrive to highly interpretative neuro-fuzzy models even of very complex systems. The use of this kind of technique in modelling the control of the pressurizer of a PWR nuclear power plant allowed verify its validity and how neuro-fuzzy models so built can be useful in understanding the automatic operation of a nuclear power plant. (author)

The causative role and therapeutic potential of the kynurenine pathway in neurodegenerative disease.

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Amaral, Marta; Outeiro, Tiago F; Scrutton, Nigel S; Giorgini, Flaviano

2013-06-01

Metabolites of the kynurenine pathway (KP), which arise from the degradation of tryptophan, have been studied in detail for over a century and garnered the interest of the neuroscience community in the late 1970s and early 1980s with work uncovering the neuromodulatory potential of this pathway. Much research in the following decades has found that perturbations in the levels of KP metabolites likely contribute to the pathogenesis of several neurodegenerative diseases. More recently, it has become apparent that targeting KP enzymes, in particular kynurenine 3-monooxygenase (KMO), may hold substantial therapeutic potential for these disorders. Here we provide an overview of the KP, the neuroactive properties of KP metabolites and their role in neurodegeneration. We also discuss KMO as a therapeutic target for these disorders, and our recent resolution of the crystallographic structure of KMO, which will permit the development of new and improved KMO inhibitors which may ultimately expedite clinical application of these compounds.

Therapeutic potential of Mediator complex subunits in metabolic diseases.

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Ranjan, Amol; Ansari, Suraiya A

2018-01-01

The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Neuro-Physiological Psychotherapy (NPP): The development and application of an integrative, wrap-around service and treatment programme for maltreated children placed in adoptive and foster care placements.

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Vaughan, Jay; McCullough, Elaine; Burnell, Alan

2016-10-01

This article describes the development and application of a wrap-around, multidisciplinary, brain-based, developmental and attachment-focussed intervention for children who have experienced significant trauma in the context of their early life. It outlines the presentation of the children and families who are referred to the service and the model of treatment that they receive. In doing so, it identifies the core components underpinning Neuro-Physiological Psychotherapy (NPP) and links the application of the integrative model to research and practice in the field of neuroscience and attachment and to the use of therapeutic approaches that are beneficial to maltreated children and their adoptive parents. It highlights the need for a neuro-sequential approach that impacts all aspects of the child's life in the effort to redress the impact of developmental trauma with the aim of improving their overall functioning and their ability to develop healthy relationships into the future. © The Author(s) 2016.

Neuro tropic Melanoma: The Management of Localised Disease

International Nuclear Information System (INIS)

Croker, J.; Burmeister, B.; Foote, M.

2012-01-01

Neuro tropic melanoma is a rare subtype of cutaneous malignant melanoma. Compared with conventional melanoma, it is more locally aggressive with an increased tendency for local recurrence but less likely for nodal or distant metastases. These tumours can be a diagnostic dilemma with a variety of morphological, histopathological, and immunophenotypical expressions. The often amelanotic, benign appearance may lead to treatment issues such as late presentation, diagnostic delay, misdiagnosis, insufficient surgical margins, and recurrence with resulting poor outcome. The neuro tropic nature of the disease and prevalence in the head and neck region can result in peri neural and neural invasion along named large nerves into the brain with resulting neuropathies. Wide local excision with adjuvant radiotherapy where indicated remains the current practice for treatment with chemotherapy predominately being reserved as a salvage treatment for patients with disseminated disease.

ADAPTIVE NEURO-FUZZY INFERENCE SYSTEM FOR END MILLING

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ANGELOS P. MARKOPOULOS

2016-09-01

Full Text Available Soft computing is commonly used as a modelling method in various technological areas. Methods such as Artificial Neural Networks and Fuzzy Logic have found application in manufacturing technology as well. NeuroFuzzy systems, aimed to combine the benefits of both the aforementioned Artificial Intelligence methods, are a subject of research lately as have proven to be superior compared to other methods. In this paper an adaptive neuro-fuzzy inference system for the prediction of surface roughness in end milling is presented. Spindle speed, feed rate, depth of cut and vibrations were used as independent input variables, while roughness parameter Ra as dependent output variable. Several variations are tested and the results of the optimum system are presented. Final results indicate that the proposed model can accurately predict surface roughness, even for input that was not used in training.

Emerging trends in neuro engineering and neural computation

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Lee, Kendall; Garmestani, Hamid; Lim, Chee

2017-01-01

This book focuses on neuro-engineering and neural computing, a multi-disciplinary field of research attracting considerable attention from engineers, neuroscientists, microbiologists and material scientists. It explores a range of topics concerning the design and development of innovative neural and brain interfacing technologies, as well as novel information acquisition and processing algorithms to make sense of the acquired data. The book also highlights emerging trends and advances regarding the applications of neuro-engineering in real-world scenarios, such as neural prostheses, diagnosis of neural degenerative diseases, deep brain stimulation, biosensors, real neural network-inspired artificial neural networks (ANNs) and the predictive modeling of information flows in neuronal networks. The book is broadly divided into three main sections including: current trends in technological developments, neural computation techniques to make sense of the neural behavioral data, and application of these technologie...

Neuro-pharmacological functional MRI of epilepsy

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Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji [Okayama Univ. (Japan). School of Medicine; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

2000-03-01

We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

Neuro-pharmacological functional MRI of epilepsy

International Nuclear Information System (INIS)

Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

2000-01-01

We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

A Neuro-Fuzzy Inference System Combining Wavelet Denoising, Principal Component Analysis, and Sequential Probability Ratio Test for Sensor Monitoring

International Nuclear Information System (INIS)

Na, Man Gyun; Oh, Seungrohk

2002-01-01

A neuro-fuzzy inference system combined with the wavelet denoising, principal component analysis (PCA), and sequential probability ratio test (SPRT) methods has been developed to monitor the relevant sensor using the information of other sensors. The parameters of the neuro-fuzzy inference system that estimates the relevant sensor signal are optimized by a genetic algorithm and a least-squares algorithm. The wavelet denoising technique was applied to remove noise components in input signals into the neuro-fuzzy system. By reducing the dimension of an input space into the neuro-fuzzy system without losing a significant amount of information, the PCA was used to reduce the time necessary to train the neuro-fuzzy system, simplify the structure of the neuro-fuzzy inference system, and also, make easy the selection of the input signals into the neuro-fuzzy system. By using the residual signals between the estimated signals and the measured signals, the SPRT is applied to detect whether the sensors are degraded or not. The proposed sensor-monitoring algorithm was verified through applications to the pressurizer water level, the pressurizer pressure, and the hot-leg temperature sensors in pressurized water reactors

Development of Optically Active Nanostructures for Potential Applications in Sensing, Therapeutics and Imaging

Science.gov (United States)

Joshi, Padmanabh

Materials at nanoscale are finding manifold applications in the various fields like sensing, plasmonics, therapeutics, to mention a few. Large amount of development has taken place regarding synthesis and exploring the novel applications of the various types of nanomaterials like organic, inorganic and hybrid of both. Yet, it is believed that the full potential of different nanomaterials is yet to be fully established stimulating researchers to explore more in the field of nanotechnology. Building on the same premise, in the following studies we have developed the nanomaterials in the class of optically active nanoparticles. First part of the study we have successfully designed, synthesized, and characterized Ag-Fe3O4 nanocomposite substrate for potential applications in quantitative Surface Enhanced Raman Scattering (SERS) measurements. Quantitative SERS-based detection of dopamine was performed successfully. In subsequent study, facile, single-step synthesis of polyethyleneimine (PEI) coated lanthanide based NaYF4 (Yb, Er) nanoparticles was developed and their application as potential photodynamic therapy agent was studied using excitations by light in near infra-red and visible region. In the following and last study, synthesis and characterization of the conjugated polymer nanoparticles was attempted successfully. Functionalization of the conjugated nanoparticles, which is a bottleneck for their potential applications, was successfully performed by encapsulating them in the silica nanoparticles, surface of which was then functionalized by amine group. Three types of optically active nanoparticles were developed for potential applications in sensing, therapeutics and imaging.

Diffusion-weighted MR imaging of neuro-Behcet's disease: a case report

International Nuclear Information System (INIS)

Hiwatashi, Akio; Moritani, Toshio; Kinoshita, Toshibumi; Westesson, Per-Lennart; Garber, Todd

2003-01-01

We present a serial study of diffusion-weighted imaging (DWI) in a patient with neuro-Behcet's disease. Initial T2-weighted magnetic resonance images showed a hyperintense lesion in the brain stem. The lesion was slightly hyperintense on DWI and the apparent diffusion coefficient (ADC) was slightly increased. Ten months later, DWI showed an improvement in the abnormal signal intensity and the region of increased ADC had increased in size, especially on the left side. DWI is useful for differentiating an acute exacerbation of neuro-Behcet's disease from acute infarction. (orig.)

NeuroElectro: A Window to the World's Neuron Electrophysiology Data

Directory of Open Access Journals (Sweden)

Shreejoy J Tripathy

2014-04-01

Full Text Available The behavior of neural circuits is determined largely by the electrophysiological properties of the neurons they contain. Understanding the relationships of these properties requires the ability to first identify and catalog each property. However, information about such properties is largely locked away in decades of closed-access journal articles with heterogeneous conventions for reporting results, making it difficult to utilize the underlying data. We solve this problem through the NeuroElectro project: a Python library, RESTful API, and web application (at http://neuroelectro.org for the extraction, visualization, and summarization of published data on neurons' electrophysiological properties. Information is organized both by neuron type (using neuron definitions provided by NeuroLex and by electrophysiological property (using a newly developed ontology. We describe the techniques and challenges associated with the automated extraction of tabular electrophysiological data and methodological metadata from journal articles. We further discuss strategies for how to best combine, normalize and organize data across these heterogeneous sources. NeuroElectro is a valuable resource for experimental physiologists looking to supplement their own data, for computational modelers looking to constrain their model parameters, and for theoreticians searching for undiscovered relationships among neurons and their properties.

A groundwork for allostatic neuro-education

OpenAIRE

Gerdes, Lee; Tegeler, Charles H.; Lee, Sung W.

2015-01-01

We propose to enliven educational practice by marrying a conception of education as guided human development, to an advanced scientific understanding of the brain known as allostasis (stability through change). The result is a groundwork for allostatic neuro-education (GANE). Education as development encompasses practices including the organic (homeschooling and related traditions), cognitive acquisition (emphasis on standards and testing), and the constructivist (aimed to support adaptive cr...

Insights into the Antimicrobial Properties of Hepcidins: Advantages and Drawbacks as Potential Therapeutic Agents

Directory of Open Access Journals (Sweden)

Lisa Lombardi

2015-04-01

Full Text Available The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by host proteases or inhibition by host body fluid composition, potential toxicity, and high production costs. This review focuses on the hepcidins, which are peptides produced by the human liver with a known role in iron homeostasis, as well by numerous other organisms (including fish, reptiles, other mammals, and their potential as antibacterial and antifungal agents. Interestingly, the antimicrobial properties of human hepcidins are enhanced at acidic pH, rendering these peptides appealing for the design of new drugs targeting infections that occur in body areas with acidic physiological pH. This review not only considers current research on the direct killing activity of these peptides, but evaluates the potential application of these molecules as coating agents preventing biofilm formation and critically assesses technical obstacles preventing their therapeutic application.

Medicinal plants growing in the Judea region: network approach for searching potential therapeutic targets

Directory of Open Access Journals (Sweden)

Arie Budovsky

2012-09-01

Full Text Available Plants growing in the Judea region are widely used in traditional medicine of the Levant region. Nevertheless, they have not so far been sufficiently analyzed and their medicinal potential has not been evaluated. This study is the first attempt to fill the gap in the knowledge of the plants growing in the region. Comprehensive data mining of online botanical databases and peer-reviewed scientific literature including ethno-pharmacological surveys from the Levant region was applied to compile a full list of plants growing in the Judea region, with the focus on their medicinal applications. Around 1300 plants growing in the Judea region were identified. Of them, 25% have medicinal applications which were analyzed in this study. Screening for chemical-protein interactions, together with the network-based analysis of potential targets, will facilitate discovery and therapeutic applications of the Judea region plants. Such an approach could also be applied as an integrative platform for further searching the potential therapeutic targets of plants growing in other regions of the world.

Potential prospects of nanomedicine for targeted therapeutics in inflammatory bowel diseases.

Science.gov (United States)

Pichai, Madharasi V A; Ferguson, Lynnette R

2012-06-21

Inflammatory bowel diseases (IBDs) such as Crohn's disease are highly debilitating. There are inconsistencies in response to and side effects in the current conventional medications, failures in adequate drug delivery, and the lack of therapeutics to offer complete remission in the presently available treatments of IBD. This suggests the need to explore beyond the horizons of conventional approaches in IBD therapeutics. This review examines the arena of the evolving IBD nanomedicine, studied so far in animal and in vitro models, before comprehensive clinical testing in humans. The investigations carried out so far in IBD models have provided substantial evidence of the nanotherapeutic approach as having the potential to overcome some of the current drawbacks to conventional IBD therapy. We analyze the pros and cons of nanotechnology in IBD therapies studied in different models, aimed at different targets and mechanisms of IBD pathogenesis, in an attempt to predict its possible impact in humans.

Emerging therapeutic potential of graviola and its constituents in cancers.

Science.gov (United States)

Qazi, Asif Khurshid; Siddiqui, Jawed A; Jahan, Rahat; Chaudhary, Sanjib; Walker, Larry A; Sayed, Zafar; Jones, Dwight T; Batra, Surinder K; Macha, Muzafar A

2018-04-05

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

DART MS based chemical profiling for therapeutic potential of Piper betle landraces.

Science.gov (United States)

Bajpai, Vikas; Pandey, Renu; Negi, Mahendra Pal Singh; Kumar, Nikhil; Kumar, Brijesh

2012-12-01

Piper betle Linn. leaves are traditionally used as a folk medicine in India and other Asiatic countries. Twenty-one P. betle landraces were analyzed using a Direct Analysis in Real Time (DART) mass spectral technique and evaluated on the basis of molecules detected in the leaves. Clustering of landraces based on three well known biologically active phenols (m/z 151,165,193) showed two broad groups with high and low phenol contents suggesting differences in their therapeutic potential. Findings of this study could be useful in rapid screening of the landraces for determining their medicinal potential and optimum utilization of the bioresource.

Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

Science.gov (United States)

Brzóska, Malgorzata M; Borowska, Sylwia; Tomczyk, Michal

2016-01-01

Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

Aquatic intervention in children with neuro-motor impairments

NARCIS (Netherlands)

Getz, M.D.

2006-01-01

The present thesis addresses the influence of aquatic interventions on motor performance of children with neuro-motor deficiencies in a functional context. The theoretical framework is based on a functional approach in compliance to the International Classification of Function and Disability (ICF).

Performance evaluation and calibration of the neuro-pet scanner

International Nuclear Information System (INIS)

Sank, V.J.; Brooks, R.A.; Cascio, H.E.; Di Chiro, G.; Friauf, W.S.; Leighton, S.B.

1983-01-01

The Neuro-PET is a circular ring seven-slice positron emission tomograph designed for imaging human heads and small animals. The scanner uses 512 bismuth germanate detectors 8.25 mm wide packed tightly together in four layers to achieve high spatial resolution (6-7 mm FWHM) without the use of beam blockers. Because of the small 38 cm ring diameter, the sensitivity is also very high: 70,000 c/s per true slice with medium energy threshold (375 keV) for a 20 cm diameter phantom containing 1 μCi/cc of positron-emitting activity, according to a preliminary measurement. There are three switch-selectable thresholds, and the sensitivity will be higher in the low threshold setting. The Neuro-PET is calibrated with a round or elliptical phantom that approximates a patient's head; this method eliminates the effects of scatter and self-attenuation to first order. Further software corrections for these artifacts are made in the reconstruction program, which reduce the measured scatter to zero, as determined with a 5 cm cold spot. With a 1 cm cold spot, the apparent activity at the center of the cold spot is 18% of the surrounding activity, which is clearly a consequence of the limits of spatial resolution, rather than scatter. The Neuro-PET has been in clinical operation since June 1982, and approximately 30 patients have been scanned to date

Using neuro-fuzzy based method to develop nuclear turbine cycle model

International Nuclear Information System (INIS)

Chan Yeakuang; Chang Chinjang

2009-01-01

The purpose of this study is to describe a hybrid soft-computing modeling technique used to develop the steam turbine cycle model for nuclear power plants. The technique uses neuro-fuzzy model to predict the generator output. Firstly, the plant past three fuel cycles operating data above 95% load were collected and validated as the baseline performance data set. Then the signal errors for new operating data were detected by comparison with the baseline data set and their allowable range of variations. Finally, the most important parameters were selected as an input of the neuro-fuzzy based steam turbine cycle model. After training and testing with key parameters (i.e. throttle pressure, condenser backpressure, feedwater flow rate, and final feedwater temperature), the proposed model can be used to predict the generator output. The analysis results show this neuro-fuzzy based turbine cycle model can be used to predict the generator output with a good agreement. Moreover, the achievement of this study provides an alternative approach in thermal performance evaluation for nuclear power plants. (author)

NeuroLines: A Subway Map Metaphor for Visualizing Nanoscale Neuronal Connectivity.

Science.gov (United States)

Al-Awami, Ali K; Beyer, Johanna; Strobelt, Hendrik; Kasthuri, Narayanan; Lichtman, Jeff W; Pfister, Hanspeter; Hadwiger, Markus

2014-12-01

We present NeuroLines, a novel visualization technique designed for scalable detailed analysis of neuronal connectivity at the nanoscale level. The topology of 3D brain tissue data is abstracted into a multi-scale, relative distance-preserving subway map visualization that allows domain scientists to conduct an interactive analysis of neurons and their connectivity. Nanoscale connectomics aims at reverse-engineering the wiring of the brain. Reconstructing and analyzing the detailed connectivity of neurons and neurites (axons, dendrites) will be crucial for understanding the brain and its development and diseases. However, the enormous scale and complexity of nanoscale neuronal connectivity pose big challenges to existing visualization techniques in terms of scalability. NeuroLines offers a scalable visualization framework that can interactively render thousands of neurites, and that supports the detailed analysis of neuronal structures and their connectivity. We describe and analyze the design of NeuroLines based on two real-world use-cases of our collaborators in developmental neuroscience, and investigate its scalability to large-scale neuronal connectivity data.

Gradual nerve elongation affects nerve cell bodies and neuro-muscular junctions.

Science.gov (United States)

Kazuo Ikeda, K I; Masaki Matsuda, M M; Daisuke Yamauchi, D Y; Katsuro Tomita, K T; Shigenori Tanaka, S T

2005-07-01

The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

NeuroLines: A Subway Map Metaphor for Visualizing Nanoscale Neuronal Connectivity

KAUST Repository

Al-Awami, Ali K.; Beyer, Johanna; Strobelt, Hendrik; Kasthuri, Narayanan; Lichtman, Jeff W.; Pfister, Hanspeter; Hadwiger, Markus

2014-01-01

We present NeuroLines, a novel visualization technique designed for scalable detailed analysis of neuronal connectivity at the nanoscale level. The topology of 3D brain tissue data is abstracted into a multi-scale, relative distance-preserving subway map visualization that allows domain scientists to conduct an interactive analysis of neurons and their connectivity. Nanoscale connectomics aims at reverse-engineering the wiring of the brain. Reconstructing and analyzing the detailed connectivity of neurons and neurites (axons, dendrites) will be crucial for understanding the brain and its development and diseases. However, the enormous scale and complexity of nanoscale neuronal connectivity pose big challenges to existing visualization techniques in terms of scalability. NeuroLines offers a scalable visualization framework that can interactively render thousands of neurites, and that supports the detailed analysis of neuronal structures and their connectivity. We describe and analyze the design of NeuroLines based on two real-world use-cases of our collaborators in developmental neuroscience, and investigate its scalability to large-scale neuronal connectivity data.

NeuroLines: A Subway Map Metaphor for Visualizing Nanoscale Neuronal Connectivity

KAUST Repository

Al-Awami, Ali K.

2014-12-31

We present NeuroLines, a novel visualization technique designed for scalable detailed analysis of neuronal connectivity at the nanoscale level. The topology of 3D brain tissue data is abstracted into a multi-scale, relative distance-preserving subway map visualization that allows domain scientists to conduct an interactive analysis of neurons and their connectivity. Nanoscale connectomics aims at reverse-engineering the wiring of the brain. Reconstructing and analyzing the detailed connectivity of neurons and neurites (axons, dendrites) will be crucial for understanding the brain and its development and diseases. However, the enormous scale and complexity of nanoscale neuronal connectivity pose big challenges to existing visualization techniques in terms of scalability. NeuroLines offers a scalable visualization framework that can interactively render thousands of neurites, and that supports the detailed analysis of neuronal structures and their connectivity. We describe and analyze the design of NeuroLines based on two real-world use-cases of our collaborators in developmental neuroscience, and investigate its scalability to large-scale neuronal connectivity data.

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

KAUST Repository

Jourdain, P.

2016-02-19

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

KAUST Repository

Jourdain, P.; Allaman, I.; Rothenfusser, K.; Fiumelli, Hubert; Marquet, P.; Magistretti, Pierre J.

2016-01-01

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

Ensemble empirical model decomposition and neuro-fuzzy conjunction model for middle and long-term runoff forecast

Science.gov (United States)

Tan, Q.

2017-12-01

Forecasting the runoff over longer periods, such as months and years, is one of the important tasks for hydrologists and water resource managers to maximize the potential of the limited water. However, due to the nonlinear and nonstationary characteristic of the natural runoff, it is hard to forecast the middle and long-term runoff with a satisfactory accuracy. It has been proven that the forecast performance can be improved by using signal decomposition techniques to product more cleaner signals as model inputs. In this study, a new conjunction model (EEMD-neuro-fuzzy) with adaptive ability is proposed. The ensemble empirical model decomposition (EEMD) is used to decompose the runoff time series into several components, which are with different frequencies and more cleaner than the original time series. Then the neuro-fuzzy model is developed for each component. The final forecast results can be obtained by summing the outputs of all neuro-fuzzy models. Unlike the conventional forecast model, the decomposition and forecast models in this study are adjusted adaptively as long as new runoff information is added. The proposed models are applied to forecast the monthly runoff of Yichang station, located in Yangtze River of China. The results show that the performance of adaptive forecast model we proposed outperforms than the conventional forecast model, the Nash-Sutcliffe efficiency coefficient can reach to 0.9392. Due to its ability to process the nonstationary data, the forecast accuracy, especially in flood season, is improved significantly.

DESARROLLO DE UN SISTEMA DE NEURO-MERCADOTECNIA USANDO EL DISPOSITIVO EMOTIV-EPOC

OpenAIRE

Luz Ángela Moreno; César Augusto Peña; Oscar Eduardo Gualdron

2014-01-01

Este artículo presenta los avances concebidos en la realización de un sistema de neuro-mercadotecnia. El objetivo del sistema es permitir evaluar las emociones que presentan los televidentes al observar comerciales publicitarios. Se hace uso de la interfaz cerebro-computador Emotiv-EPOC para la adquisición de las neuro-señales. Se describen los algoritmos empleados para el análisis de las pautas publicitarias. Se presentan unas pruebas experimentales donde se comparan los resultados obtenidos...

From Psycho-Economics to Neuro-Economics

OpenAIRE

Bernard WALLISER

2012-01-01

In economics, three nested organizational levels, namely behavioural, mental and neural, can be distinguished. They introduce specific theoretical or observable concepts and suggest their own models for choice making. If psycho-economics relates implemented actions to declared mental states, neuro-economics relates mental states to brain areas. Bridge principles can be defined which link concepts with similar interpretations at two successive levels. Thanks to these principles, relations or e...

Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

Directory of Open Access Journals (Sweden)

José Manuel Calderón-Montaño

2014-01-01

Full Text Available Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

Video-Teleconferencing in Pediatric Neuro-Oncology: Ten Years of Experience

Directory of Open Access Journals (Sweden)

Nisreen Amayiri

2017-04-01

Full Text Available Purpose: The management of central nervous system tumors is challenging in low- and middle-income countries. Little is known about applicability of twinning initiatives with high-income countries in neuro-oncology. In 2004, a monthly neuro-oncology video-teleconference program was started between King Hussein Cancer Center (Amman, Jordan and the Hospital for Sick Children (Toronto, Ontario, Canada. More than 100 conferences were held and > 400 cases were discussed. The aim of this work was to assess the sustainability of such an initiative and the evolution of the impact over time. Methods: We divided the duration in to three eras according to the initial 2 to 3 years of work of three consecutive oncologists in charge of the neuro-oncology program at King Hussein Cancer Center. We retrospectively reviewed the written minutes and compared the preconference suggested plans with the postconference recommendations. Impact of changes on the patient care was recorded. Results: Thirty-three sets of written minutes (covering 161 cases in the middle era and 32 sets of written minutes (covering 122 cases in the last era were compared with the initial experience (20 meetings, 72 cases. Running costs of these conferences has dropped from $360/h to < $40/h. Important concepts were introduced, such as multidisciplinary teamwork, second-look surgery, and early referral. Suggestions for plan changes have decreased from 44% to 30% and 24% in the respective consecutive eras. Most recommendations involved alternative intervention modalities or pathology review. Most of these recommendations were followed. Conclusion: Video-teleconferencing in neuro-oncology is feasible and sustainable. With time, team experience is built while the percentage and the type of treatment modifications change. Commitment and motivation helped maintain this initiative rather than availability of financial resources. Improvement in patients’ care was achieved, in particular, with the

Temporal Explorations in Cosmic Consciousness: Intra-Agential Entanglements and the Neuro-Image

Directory of Open Access Journals (Sweden)

Patricia Pisters

2015-11-01

Full Text Available When Deleuze in the 1980s argued that ‘the brain is the screen’ he introduced the concepts of movement-image and time-image, two different modes of cinema with particular ontological and aesthetic characteristics. Contemporary cinema, however, has moved into yet another aesthetic mode, which I have proposed to call the neuro-image. One of the characteristics of the neuro-image is that we no longer follow the movements and actions of characters in a certain space (as in the movement-image, nor see the world coloured through their eyes (as in the time-image, but we (often quite literally experience brain worlds more directly, from within mental landscapes. In this essay I will investigate in which ways these brain worlds aesthetically express an embodied and embedded brain, addressing the new materialist dimensions of the neuro-image in a journey of cosmic cinema and, to speak with Barad, ‘meeting the universe halfway.’

A Neuro-Control Design Based on Fuzzy Reinforcement Learning

DEFF Research Database (Denmark)

Katebi, S.D.; Blanke, M.

This paper describes a neuro-control fuzzy critic design procedure based on reinforcement learning. An important component of the proposed intelligent control configuration is the fuzzy credit assignment unit which acts as a critic, and through fuzzy implications provides adjustment mechanisms....... The fuzzy credit assignment unit comprises a fuzzy system with the appropriate fuzzification, knowledge base and defuzzification components. When an external reinforcement signal (a failure signal) is received, sequences of control actions are evaluated and modified by the action applier unit. The desirable...... ones instruct the neuro-control unit to adjust its weights and are simultaneously stored in the memory unit during the training phase. In response to the internal reinforcement signal (set point threshold deviation), the stored information is retrieved by the action applier unit and utilized for re...

Protective effect of methanol extract of Uncaria rhynchophylla against excitotoxicity induced by N-methyl-D-aspartate in rat hippocampus.

Science.gov (United States)

Lee, Jongseok; Son, Dongwook; Lee, Pyeongjae; Kim, Dae-Keun; Shin, Min-Chul; Jang, Mi-Hyeon; Kim, Chang-Ju; Kim, Yong-Sik; Kim, Sun-Yeou; Kim, Hocheol

2003-05-01

Uncaria rhynchophylla is a medicinal herb used for convulsive disorders in Oriental medicine. In this study, the effect of the methanol extract of Uncaria rhynchophylla against N-methyl-D-aspartate (NMDA)-induced excitotoxicity was investigated. Pretreatment with the extract of Uncaria rhynchopylla reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. In the patch clamp study, Uncaria rhynchophylla significantly inhibited NMDA receptor-activated ion current in acutely dissociated hippocampal CA1 neurons. These results indicate that Uncaria rhynchophylla offers protection against NMDA-induced neuronal injury and inhibitory action on NMDA receptor-mediated ion current may be a mechanism behind the neuroprotective effect of Uncaria rhynchophylla.

Aptamer nanomedicine for cancer therapeutics: barriers and potential for translation.

Science.gov (United States)

Lao, Yeh-Hsing; Phua, Kyle K L; Leong, Kam W

2015-03-24

Aptamer nanomedicine, including therapeutic aptamers and aptamer nanocomplexes, is beginning to fulfill its potential in both clinical trials and preclinical studies. Especially in oncology, aptamer nanomedicine may perform better than conventional or antibody-based chemotherapeutics due to specificity compared to the former and stability compared to the latter. Many proof-of-concept studies on applying aptamers to drug delivery, gene therapy, and cancer imaging have shown promising efficacy and impressive safety in vivo toward translation. Yet, there remains ample room for improvement and critical barriers to be addressed. In this review, we will first introduce the recent progress in clinical trials of aptamer nanomedicine, followed by a discussion of the barriers at the design and in vivo application stages. We will then highlight recent advances and engineering strategies proposed to tackle these barriers. Aptamer cancer nanomedicine has the potential to address one of the most important healthcare issues of the society.

Quality of life research in neuro-oncology: a quantitative comparison.

Science.gov (United States)

Klein, Elizabeth; Altshuler, David; Hallock, Abhirami; Szerlip, Nicholas

2014-01-01

Our understanding of the biology of neuro-oncologic disease has improved vastly over time, however overall patient survival remains relatively poor. Our goal as clinicians, therefore, should be to ensure that the quality of life (QOL) in that survival time is optimized. Here we review neuro-oncology QOL abstracts presented at major oncology conferences and the published literature to make a quantitative comparison to other common cancer subtypes. First, all abstracts presented at major oncology meetings from 2008 to 2012 were reviewed and filtered to find those related to QOL in CNS, breast, lung, and prostate cancer. Next, a Medline search was performed to identify all QOL papers published from 2003 to 2012 for the same cancer subtypes. The results were compared as absolute values and percentages. The average percentage of CNS QOL-related abstracts presented at ASCO and ASTRO over the last 5 years was 4.9 %, compared to 6.4 % for breast, 4.4 % for lung, and 6.1 % for prostate. There is a significant difference in total percentage of QOL abstracts over the time period when comparing CNS to breast and prostate, but not lung (p neuro-oncology research. We need to improve this by standardizing QOL measures and including them in every outcome study.

Combination therapy of potential gene to enhance oral cancer therapeutic effect

Science.gov (United States)

Yeh, Chia-Hsien; Hsu, Yih-Chih

2015-03-01

The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

Comparative analysis of the effect of low-dimensional alumina structures on cell lines L929 and Neuro-2a

Energy Technology Data Exchange (ETDEWEB)

Fomenko, A. N., E-mail: alserova@ispms.tsc.ru; Korovin, M. S., E-mail: msk@ispms.tsc.ru [National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation)

2016-08-02

The paper presents the toxicity evaluation of nanostructures on the basis of alumina of different shape (nanofibers, nanoplates, nanosheets, nanosheet agglomerates) and with similar physical and chemical properties (particle size, specific surface area, phase composition, and zeta potential). The nanostructures were examined by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), low-temperature nitrogen adsorption, and dynamic light scattering (DLS). The cytotoxicity of nanostructures was estimated using L929 fibroblast cells and Neuro-2a tumor cells. It has been found that the L929 cells are less subject to the influence of alumina nanoparticles than the Neuro-2a tumor cells. Probably, the differences in the proliferation activity of normal and tumor cells in contact with the synthesized nanostructures are due to a change in the pH of the cell microenvironment.

Investigating Therapeutic Potential of Trigonella foenum-graecum L. as Our Defense Mechanism against Several Human Diseases

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Shivangi Goyal

2016-01-01

Full Text Available Current lifestyle, stress, and pollution have dramatically enhanced the progression of several diseases in human. Globally, scientists are looking for therapeutic agents that can either cure or delay the onset of diseases. Medicinal plants from time immemorial have been used frequently in therapeutics. Of many such plants, fenugreek is one of the oldest herbs which have been identified as an important medicinal plant by the researchers around the world. It is potentially beneficial in a number of diseases such as diabetes, hypercholesterolemia, and inflammation and probably in several kinds of cancers. It has industrial applications such as synthesis of steroidal hormones. Its medicinal properties and their role in clinical domain can be attributed to its chemical constituents. The 3 major chemical constituents which have been identified as responsible for principle health effects are galactomannan, 4-OH isoleucine, and steroidal saponin. Numerous experiments have been carried out in vivo and in vitro for beneficial effects of both the crude chemical and of its active constituent. Due to its role in health care, the functional food industry has referred to it as a potential nutraceutical. This paper is about various medicinal benefits of fenugreek and its potential application as therapeutic agent against several diseases.

Neuro-fuzzy Control of Integrating Processes

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Anna Vasičkaninová

2011-11-01

Full Text Available Fuzzy technology is adaptive and easily applicable in different areas.Fuzzy logic provides powerful tools to capture the perceptionof natural phenomena. The paper deals with tuning of neuro-fuzzy controllers for integrating plant and for integrating plantswith time delay. The designed approach is verified on three examples by simulations and compared plants with classical PID control.Designed fuzzy controllers lead to better closed-loop control responses then classical PID controllers.

Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

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Mostafa Wanees Ahmed El husseny

2017-01-01

Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy

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Ágatha Oliveira-Giacomelli

2018-04-01

Full Text Available Since proving adenosine triphosphate (ATP functions as a neurotransmitter in neuron/glia interactions, the purinergic system has been more intensely studied within the scope of the central nervous system. In neurological disorders with associated motor symptoms, including Parkinson's disease (PD, motor neuron diseases (MND, multiple sclerosis (MS, amyotrophic lateral sclerosis (ALS, Huntington's Disease (HD, restless leg syndrome (RLS, and ataxias, alterations in purinergic receptor expression and activity have been noted, indicating a potential role for this system in disease etiology and progression. In neurodegenerative conditions, neural cell death provokes extensive ATP release and alters calcium signaling through purinergic receptor modulation. Consequently, neuroinflammatory responses, excitotoxicity and apoptosis are directly or indirectly induced. This review analyzes currently available data, which suggests involvement of the purinergic system in neuro-associated motor dysfunctions and underlying mechanisms. Possible targets for pharmacological interventions are also discussed.

MRI Overestimates Excitotoxic Amygdala Lesion Damage in Rhesus Monkeys

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Benjamin M. Basile

2017-06-01

Full Text Available Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for determining the causal contributions of different brain areas to behavior. For nonhuman primates especially, it is advantageous to keep subjects with high-quality lesions alive and contributing to science for many years. However, this requires the ability to estimate lesion extent accurately. Previous research has shown that in vivo T2-weighted magnetic resonance imaging (MRI accurately estimates damage following selective ibotenic acid lesions of the hippocampus. Here, we show that the same does not apply to lesions of the amygdala. Across 19 hemispheres from 13 rhesus monkeys, MRI assessment consistently overestimated amygdala damage as assessed by microscopic examination of Nissl-stained histological material. Two outliers suggested a linear relation for lower damage levels, and values of unintended amygdala damage from a previous study fell directly on that regression line, demonstrating that T2 hypersignal accurately predicts damage levels below 50%. For unintended damage, MRI estimates correlated with histological assessment for entorhinal cortex, perirhinal cortex and hippocampus, though MRI significantly overestimated the extent of that damage in all structures. Nevertheless, ibotenic acid injections routinely produced extensive intentional amygdala damage with minimal unintended damage to surrounding structures, validating the general success of the technique. The field will benefit from more research into in vivo lesion assessment techniques, and additional evaluation of the accuracy of MRI assessment in different brain areas. For now, in vivo MRI assessment of ibotenic acid lesions of the amygdala can be used to confirm successful injections, but MRI estimates of lesion extent should be interpreted with caution.

Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries.

Science.gov (United States)

Vieira, M H C; Oliveira, R J; Eça, L P M; Pereira, I S O; Hermeto, L C; Matuo, R; Fernandes, W S; Silva, R A; Antoniolli, A C M B

2014-12-12

Rupture of the Achilles tendon diminishes quality of life. The gold-standard therapy is a surgical suture, but this presents complications, including wound formation and inflammation. These complications spurred evaluation of the therapeutic potential of mesenchymal stem cells (MSCs) from adipose tissue. New Zealand rabbits were divided into 6 groups (three treatments with two time points each) evaluated at either 14 or 28 days after surgery: cross section of the Achilles tendon (CSAT); CSAT + Suture; and CSAT + MSC. A comparison between all groups at both time points showed a statistically significant increase in capillaries and in the structural organization of collagen in the healed tendon in the CSAT + Suture and CSAT + MSC groups at the 14-day assessment. Comparison between the two time points within the same group showed a statistically significant decrease in the inflammatory process and an increase in the structural organization of collagen in the CSAT and CSAT + MSC groups. A study of the genomic integrity of the cells suggested a linear correlation between an increase of injuries and culture time. Thus, MSC transplantation is a good alternative for treatment of Achilles tendon ruptures because it may be conducted without surgery and tendon suture and, therefore, has no risk of adverse effects resulting from the surgical wound or inflammation caused by nonabsorbable sutures. Furthermore, this alternative treatment exhibits a better capacity for wound healing and maintaining the original tendon architecture, depending on the arrangement of the collagen fibers, and has important therapeutic potential.

Evidence Report: Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

Science.gov (United States)

Stenger, Michael B.; Tarver, William J.; Brunstetter, Tyson; Gibson, Charles Robert; Laurie, Steven S.; Lee, Stuart M. C.; Macias, Brandon R.; Mader, Thomas H.; Otto, Christian; Smith, Scott M.;

A POST-MODERNIST ANALYSIS OF THE NEURO-SCIENCES ...

African Journals Online (AJOL)

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Senior Lecturer, Department of Psychology, Rand Afrikaans University. Anita Stuart. D Litt et Phil ... of neuro-science, including the assumptive framework upon which the dominant discourse in this field is based, which ultimately serves to maintain .... 1978:52; 1979:67). Each narrative or text, once embraced, “invites certain.

Breast, prostate, and cervical cancer, melanoma, and neuro

African Journals Online (AJOL)

cancer, melanoma, and neuro-endocrine tumours. Nuclear medicine ... for the evaluation of the presence and localisation of skeletal metastases .... is primarily a surgical/histological diagnosis ... and 50 - 70% for pancreatic NETs, and a high speci ... Steyn and Dr A Brink for their assistance in writing this article. References.

Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma

International Nuclear Information System (INIS)

Milas, Luka; Saito, Yoshihiro; Hunter, Nancy; Milross, Christopher G.; Mason, Kathryn A.

1996-01-01

Background. Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G 2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Methods. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD 50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Results. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD 50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Conclusions. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain

DESARROLLO DE UN SISTEMA DE NEURO-MERCADOTECNIA USANDO EL DISPOSITIVO EMOTIV-EPOC

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Luz Ángela Moreno

2014-11-01

Full Text Available Este artículo presenta los avances concebidos en la realización de un sistema de neuro-mercadotecnia. El objetivo del sistema es permitir evaluar las emociones que presentan los televidentes al observar comerciales publicitarios. Se hace uso de la interfaz cerebro-computador Emotiv-EPOC para la adquisición de las neuro-señales. Se describen los algoritmos empleados para el análisis de las pautas publicitarias. Se presentan unas pruebas experimentales donde se comparan los resultados obtenidos por métodos tradicionales con las propuestas.

Neuro-ophthalmologic evaluation, quality of life, and functional disability in patients with MS.

Science.gov (United States)

Garcia-Martin, Elena; Rodriguez-Mena, Diego; Herrero, Raquel; Almarcegui, Carmen; Dolz, Isabel; Martin, Jesus; Ara, Jose R; Larrosa, Jose M; Polo, Vicente; Fernández, Javier; Pablo, Luis E

2013-07-02

To evaluate correlations between longitudinal changes in neuro-ophthalmologic measures and quality of life (QOL) and disability in patients with multiple sclerosis (MS), using optical coherence tomography (OCT), visual evoked potentials (VEP), and visual field examination. Fifty-four patients with relapsing-remitting MS were enrolled in this study and underwent Multiple Sclerosis Quality of Life questionnaire (54 items) (MSQOL-54) and Expanded Disability Status Scale (EDSS) evaluation, as well as complete neuro-ophthalmologic examination including visual field testing and retinal nerve fiber layer (RNFL) measurements using Cirrus and Spectralis OCT and VEP. All patients were re-evaluated at 12, 24, and 36 months. Logistical regression was performed to analyze which measures, if any, could predict QOL. Overall, RNFL thickness results at the baseline evaluation were significantly different from those at 3 years (p ≤ 0.05), but there were no differences in functional measures (visual acuity, contrast sensitivity, color vision, visual field, and VEP). A reduced MSQOL-54 score was associated with an increase in EDSS score and a decrease in both functional and structural parameters. Patients with longer MS duration presented with a lower MSQOL-54 score (reduction in QOL). Patients with progressive axonal loss as seen in RNFL results had a lower QOL and more functional disability.

Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

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Zhao Han

Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

Neuro-Behcet's disease: diagnostic usefulness of MR imaging

International Nuclear Information System (INIS)

Kim, Song Soo; Song, Chang June; Lee, Ae Young; Pak, Chung Ho

2000-01-01

To suggest the characteristic MR features and to evaluate the usefulness of MR imaging for the diagnosis of neuro-Behcet's disease. We retrospectively reviewed the MR findings of clinically confirmed neuro-Behcet's disease in eight patients (M:F =3D 7:1) ranging in age from 28 to 47 (average, 36) years. The findings were analyzed in terms of the most frequently occurring sites, signal intensities, contrast enhancement, and the changing patterns seen on follow-up MR examination. Seven of the eight patients had parenchymal brain lesions and the other had dural sinus thrombosis without brain parenchymal brain abnormality. In descending order of frequency, lesions involved the pons, midbrain, medulla oblongata, internal capsule, basal ganglia, thalamus, temporal lobe, and corpus callosum. The brain stem was involved in six patients, five of whom showed extensive involvement of the entire stem. In five patients, brain stem lesions showed supratentorial involvement, and in one, involvement of this region only was noted. Signal intensities of the lesions were poorly defined and extensive, especially in the brain stem, usually showed prolongation of both T1 and T2 relaxation time. Three patients underwent follow-up examination, and this showed that while most lesions had disappeared in time, some had become small and cavitary. Initial MR examination showed that three patients had newly developed lesions as well as cavitary foci, suggesting the recurrence of disease. Contrast enhancement was noted in five of seven patients (71%), and various types, including nodular, linear, marginal, and ring. The MR features of neuro-Behcet's disease were fairly characteristic, and in clinically unsuspicious patients might be diagnostically useful. (author)

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

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Neil V. Klinger

2016-01-01

Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

Neuro-Fuzzy DC Motor Speed Control Using Particle Swarm Optimization

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Boumediene ALLAOUA

2009-12-01

Full Text Available This paper presents an application of Adaptive Neuro-Fuzzy Inference System (ANFIS control for DC motor speed optimized with swarm collective intelligence. First, the controller is designed according to Fuzzy rules such that the systems are fundamentally robust. Secondly, an adaptive Neuro-Fuzzy controller of the DC motor speed is then designed and simulated; the ANFIS has the advantage of expert knowledge of the Fuzzy inference system and the learning capability of neural networks. Finally, the ANFIS is optimized by Swarm Intelligence. Digital simulation results demonstrate that the deigned ANFIS-Swarm speed controller realize a good dynamic behavior of the DC motor, a perfect speed tracking with no overshoot, give better performance and high robustness than those obtained by the ANFIS alone.

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities.

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Soler, Joaquim; Elices, Matilde; Franquesa, Alba; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Pascual, Juan C; Riba, Jordi

2016-03-01

Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca. We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice. The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.

NeuroBlocks – Visual Tracking of Segmentation and Proofreading for Large Connectomics Projects

KAUST Repository

Al-Awami, Ali

2015-08-12

In the field of connectomics, neuroscientists acquire electron microscopy volumes at nanometer resolution in order to reconstruct a detailed wiring diagram of the neurons in the brain. The resulting image volumes, which often are hundreds of terabytes in size, need to be segmented to identify cell boundaries, synapses, and important cell organelles. However, the segmentation process of a single volume is very complex, time-intensive, and usually performed using a diverse set of tools and many users. To tackle the associated challenges, this paper presents NeuroBlocks, which is a novel visualization system for tracking the state, progress, and evolution of very large volumetric segmentation data in neuroscience. NeuroBlocks is a multi-user web-based application that seamlessly integrates the diverse set of tools that neuroscientists currently use for manual and semi-automatic segmentation, proofreading, visualization, and analysis. NeuroBlocks is the first system that integrates this heterogeneous tool set, providing crucial support for the management, provenance, accountability, and auditing of large-scale segmentations. We describe the design of NeuroBlocks, starting with an analysis of the domain-specific tasks, their inherent challenges, and our subsequent task abstraction and visual representation. We demonstrate the utility of our design based on two case studies that focus on different user roles and their respective requirements for performing and tracking the progress of segmentation and proofreading in a large real-world connectomics project.

Encouraging Subspecialty Practice by Constructively Influencing Trainees Early in their Careers Will Improve Advocacy for Neuro-Ophthalmology among Nigerian Ophthalmologists

Science.gov (United States)

Ogun, Olufunmilola A.

2016-01-01

This study was conducted to assess the current knowledge, attitude, and perception of Nigerian ophthalmologists toward neuro-ophthalmology; identify barriers to the uptake of neuro-ophthalmology as a desired subspecialty; and make recommendations to improve interest in neuro-ophthalmology training. This was a cross-sectional survey of ophthalmology consultants and trainees from the six geopolitical zones of Nigeria, who were attending a national ophthalmology conference. All consenting respondents voluntarily completed a validated self-administered questionnaire. There were 107 respondents comprising 56 males and 51 females. Majority (54.2%) of respondents were aged 40 years and younger. Almost half (47.8%) worked at tertiary level, public health institutions. Only 10.3% worked in private practice. Neuro-ophthalmology exposure was short and occurred mainly during residency (65.7%), while 15% had no exposure at all. Most (80.4%) indicated only nominal interest in neuro-ophthalmology, while only 4.6% indicated a desire to specialize in the field. Financial constraint was the main obstacle to the pursuit of subspecialty training. A total of 86% of respondents admitted that full (34%) or partial (52%) Funding would motivate them to pursue the training. Among respondents desiring part sponsorship, more than half were willing to augment such sponsorship with personal funds. In conclusion, career interest in neuro-ophthalmology is very low among Nigerian ophthalmologists. Late and limited exposure to neuro-ophthalmology during medical training may be contributing factors. Early exposure to neuro-ophthalmology during medical school rotations, coupled with the provision of sponsored subspecialty training opportunities, will serve to increase enrollment in the field. PMID:29349319

Three Forms of Neuro-Realism: Explaining the Persistence of the "Uncritically Real" in Popular Neuroscience News

Science.gov (United States)

Gruber, David R.

2017-01-01

Neuro-realism is a widely cited concept describing a textual phenomenon in popular science news wherein brain research uncritically validates or invalidates the "realness" of particular beliefs or practices. Currently, no research on neuro-realism examines the variable rhetorical roles of such statements, that is, how they support…

Using neuro-fuzzy based approach for the evaluation of turbine-generator outputs

International Nuclear Information System (INIS)

Chan, Y. K.; Lu, C. C.; Chang, C. J.; Kao, L.; Hong, L. C.

2010-01-01

The objective of this study is to develop a hybrid soft-computing modeling technique used to develop the steam turbine cycle model for Chinshan Nuclear Power Station (CNPS). The technique uses neuro-fuzzy model to predict the turbine-generator output. Firstly, the station past three fuel cycles operating data above 95% load were collected and validated as the baseline performance data set. Then, the signal errors for new operating data were detected by comparison with the baseline data set and their allowable range of variations. Finally, the most important parameters were selected as an input of the neuro-fuzzy based steam turbine cycle model. After training and testing with key parameters including throttle pressure, condenser back pressure, feedwater mass flow, and final feedwater temperature, the proposed model can be applied to predict the turbine-generator output. The analysis results show this neuro-fuzzy based turbine cycle model can be used to predict the generator output with a good agreement. Moreover, the achievement of this study provides an alternative approach in thermal performance evaluation for nuclear power stations. (authors)

Micro-angiography for neuro-vascular imaging. II. Cascade model analysis

International Nuclear Information System (INIS)

Ganguly, Arundhuti; Rudin, Stephen; Bednarek, Daniel R.; Hoffmann, Kenneth R.

2003-01-01

A micro-angiographic detector was designed and its performance was previously tested to evaluate its feasibility as an improvement over current x-ray detectors for neuro-interventional imaging. The detector was shown to have a modulation transfer function value of about 2% at the Nyquist frequency of 10 cycles/mm and a zero frequency detective quantum efficiency [DQE(0)] value of about 55%. An assessment of the system was required to evaluate whether the current system was performing at its full potential and to determine if any of its components could be optimized to further improve the output. For the purpose, in this study, the parallel cascade theory was used to analyze the performance of the detector under neuro-angiographic conditions by studying the output at the various stages in the imaging chain. A simple model for the spread of light in the CsI(Tl) entrance phosphor was developed and the resolution degradation due to K-fluorescence absorption was calculated. The total gain of the system was found to result in 21 e - (rms) detected at the charge coupled device per absorbed x-ray photon. The gain and the spread of quanta in the imaging chain were used to calculate theoretically the DQE using the parallel cascade model. The results of the model-based calculations matched fairly well with the experimental data previously obtained. This model was then used to optimize the phosphor thickness for the detector. The results showed that the area under the DQE curve had a maximum value at 150 μm of CsI(Tl), though when weighted by the squared signal in frequency space of a 100-μm-diam iodinated vessel, the integral DQE reached a maximum at 250 μm of CsI(Tl). Further, possible locations for gain increase in the imaging chain were determined, and the output of the improved system was simulated. Thus a theoretical analysis for the micro-angiographic detector was performed to better assess its potential

The multifaceted therapeutic potential of benfotiamine.

Science.gov (United States)

Balakumar, Pitchai; Rohilla, Ankur; Krishan, Pawan; Solairaj, Ponnu; Thangathirupathi, Arunachalam

2010-06-01

Thiamine, known as vitamin B(1), plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine. (c) 2010 Elsevier Ltd. All rights reserved.

NEURO-FUZZY MODELING APPLIED IN PROGRAM MANAGEMENT TO INCREASE LOCAL PUBLIC ADMINISTRATION PERFORMANCE

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Adrian-Mihai Zaharia-Radulescu

2016-07-01

Full Text Available One of the challenges in local public administration is dealing with an increasing number of competing requests coming from the communities they serve. The traditional approach would be to handle each request as a standalone project and be prioritized according to benefits and budget available. More and more nowadays program management is becoming a standard approach in managing the initiatives of local public administration. Program management approach is itself an enabler for performance in public sector organizations by allowing an organization to better coordinate its efforts and resources in managing a portfolio of projects. This paper aims to present how neuro-fuzzy modeling applied in program management can help an organization to increase its performance. Neuro-fuzzy modeling would lead organizations one step further by allowing them to simulate different scenarios and manage better the risks accompanying their initiatives. The research done by the authors is theoretical and combines knowledge from different areas and a neuro-fuzzy model is proposed and discussed.

Neuro-osteoarthropathy of the Foot-Radiologist: Friend or Foe?

NARCIS (Netherlands)

Schoots, Ivo G.; Slim, Frederik J.; Busch-Westbroek, Tessa E.; Maas, Mario

2010-01-01

Charcot neuro-osteoarthropathy is a significant problem with a rapid devastating nature. If not recognized it may lead to progressive foot deformity, ulceration or osteomyelitis, or eventually to amputation. The diagnosis is challenging, and imaging plays a pivotal role. Rapid and accurate diagnosis

Brain stem type neuro-Behcet's syndrome

International Nuclear Information System (INIS)

Kataoka, Satoshi; Hirose, Genjiro; Kosoegawa, Hiroshi; Oda, Rokuhei; Yoshioka, Akira

1987-01-01

Two cases of brain stem type Neuro-Behcet's syndrome were evaluated by brain CT and Magnetic Resonance Imaging (Super-conducting type, 0.5 tesla) to correlate with the neurological findings. In the acute phase, low density area with peripheral enhancement effect and mass effect were seen at the brain stem in brain CT. MRI revealed a extensive high intensity signal area mainly involving the corticospinal tract in the meso-diencephalon as well as pons by T 2 weighted images (spin echo, TR = 1, 600 msec, TE = 90 msec) and the value of T 1 , T 2 , at the brain stem lesion were prolonged moderately. After high dose steroid treatment, the low density area in brain CT and high signal area in MRI were gradually reduced in its size. Peripheral enhancement effect in brain CT disappeared within 10 months in case 1, one month in the other case. In the chronic stage, the reduction of low density area and atrophy of brain stem were noted in brain CT. The lesion in chronic stage had low intensity in T 1 , T 2 weighted images and the T 1 , T 2 values at the lesion were mildly prolonged in MRI. Sequentially CT with enhancement and MRI examinations with T 1 , T 2 weighted images were useful to detect the lesion and to evaluate the activity, evolution of brain stem type Neuro-Behcet's syndrome. (author)

Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

Directory of Open Access Journals (Sweden)

Verónica Pérez-De La Cruz

2012-01-01

Full Text Available Quinolinic acid (QUIN, an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca 2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

Re-evaluation of Magnetic Resonance and Computerised Tomographic Imaging in Neuro-Ophthalmic Patients in an Academic Centre

NARCIS (Netherlands)

Koekoek, Clarence G. J.; Meiners, Linda C.; Pott, Jan Willem R.

The aim of the study is to report the frequency of missed diagnoses on magnetic resonance and computerised tomographic imaging in neuro-ophthalmic patients who were referred to an academic ophthalmology department, with apparent normal imaging. The authors included all neuro-ophthalmic patients,

Triactome: neuro-immune-adipose interactions. Implication in vascular biology

Directory of Open Access Journals (Sweden)

George Nikov Chaldakov

2014-04-01

Full Text Available Understanding how the precise interactions of nerves, immune cells and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae: intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue, we recently designated tunica adiposa (in brief, adiposa like intima, media, adventitia. According to present paradigm, atherosclerosis is an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. Periadventitial adipose tissue expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic signaling proteins collectively dubbed adipokines. However, the role of perivascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

NeuroMatic: An Integrated Open-Source Software Toolkit for Acquisition, Analysis and Simulation of Electrophysiological Data

Science.gov (United States)

Rothman, Jason S.; Silver, R. Angus

2018-01-01

Acquisition, analysis and simulation of electrophysiological properties of the nervous system require multiple software packages. This makes it difficult to conserve experimental metadata and track the analysis performed. It also complicates certain experimental approaches such as online analysis. To address this, we developed NeuroMatic, an open-source software toolkit that performs data acquisition (episodic, continuous and triggered recordings), data analysis (spike rasters, spontaneous event detection, curve fitting, stationarity) and simulations (stochastic synaptic transmission, synaptic short-term plasticity, integrate-and-fire and Hodgkin-Huxley-like single-compartment models). The merging of a wide range of tools into a single package facilitates a more integrated style of research, from the development of online analysis functions during data acquisition, to the simulation of synaptic conductance trains during dynamic-clamp experiments. Moreover, NeuroMatic has the advantage of working within Igor Pro, a platform-independent environment that includes an extensive library of built-in functions, a history window for reviewing the user's workflow and the ability to produce publication-quality graphics. Since its original release, NeuroMatic has been used in a wide range of scientific studies and its user base has grown considerably. NeuroMatic version 3.0 can be found at http://www.neuromatic.thinkrandom.com and https://github.com/SilverLabUCL/NeuroMatic. PMID:29670519

Neuro-fuzzy system modeling based on automatic fuzzy clustering

Institute of Scientific and Technical Information of China (English)

Yuangang TANG; Fuchun SUN; Zengqi SUN

2005-01-01

A neuro-fuzzy system model based on automatic fuzzy clustering is proposed.A hybrid model identification algorithm is also developed to decide the model structure and model parameters.The algorithm mainly includes three parts:1) Automatic fuzzy C-means (AFCM),which is applied to generate fuzzy rules automatically,and then fix on the size of the neuro-fuzzy network,by which the complexity of system design is reducesd greatly at the price of the fitting capability;2) Recursive least square estimation (RLSE).It is used to update the parameters of Takagi-Sugeno model,which is employed to describe the behavior of the system;3) Gradient descent algorithm is also proposed for the fuzzy values according to the back propagation algorithm of neural network.Finally,modeling the dynamical equation of the two-link manipulator with the proposed approach is illustrated to validate the feasibility of the method.

Modeling neuro-vascular coupling in rat cerebellum: characterization of deviations from linearity

DEFF Research Database (Denmark)

Rasmussen, Tina; Holstein-Rathlou, Niels-Henrik; Lauritzen, Martin

2009-01-01

We investigated the quantitative relation between neuronal activity and blood flow by means of a general parametric mathematical model which described the neuro-vascular system as being dynamic, linear, time-invariant, and subjected to additive noise. The model was constructed from measurements...... and dips in blood flow responses to stimulation for 60 s, and overgrowth of blood flow responses to stimulation for 600 s. In another set of experiments, stimulation frequencies were in the range 0.5-10 Hz and the stimulation duration was 15 s. The neuro-vascular system could be approximated by the linear...

How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology.

Science.gov (United States)

Ganau, Mario; Paris, Marco; Syrmos, Nikolaos; Ganau, Laura; Ligarotti, Gianfranco K I; Moghaddamjou, Ali; Prisco, Lara; Ambu, Rossano; Chibbaro, Salvatore

2018-02-26

The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1) the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2) a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3) the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.

How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology

Directory of Open Access Journals (Sweden)

Mario Ganau

2018-02-01

Full Text Available The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1 the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2 a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3 the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Alana M. Horowitz

2017-08-01

Full Text Available Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

A NEURO FUZZY MODEL FOR THE INVESTIGATION OF ...

African Journals Online (AJOL)

Several factors may contribute directly or indirectly to the structural failure of metallic pipes. The most important of which is corrosion. Corrosivity of pipes is not a directly measurable parameter as pipe corrosion is a very random phenomenon. The main aim of the present study is to develop a neuro-fuzzy model capable of ...

AN INTELLIGENT NEURO-FUZZY TERMINAL SLIDING MODE CONTROL METHOD WITH APPLICATION TO ATOMIC FORCE MICROSCOPE

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Seied Yasser Nikoo

2016-11-01

Full Text Available In this paper, a neuro-fuzzy fast terminal sliding mode control method is proposed for controlling a class of nonlinear systems with bounded uncertainties and disturbances. In this method, a nonlinear terminal sliding surface is firstly designed. Then, this sliding surface is considered as input for an adaptive neuro-fuzzy inference system which is the main controller. A proportinal-integral-derivative controller is also used to asist the neuro-fuzzy controller in order to improve the performance of the system at the begining stage of control operation. In addition, bee algorithm is used in this paper to update the weights of neuro-fuzzy system as well as the parameters of the proportinal-integral-derivative controller. The proposed control scheme is simulated for vibration control in a model of atomic force microscope system and the results are compared with conventional sliding mode controllers. The simulation results show that the chattering effect in the proposed controller is decreased in comparison with the sliding mode and the terminal sliding mode controllers. Also, the method provides the advantages of fast convergence and low model dependency compared to the conventional methods.

Neuro-fuzzy model for evaluating the performance of processes ...

Indian Academy of Sciences (India)

CHIDOZIE CHUKWUEMEKA NWOBI-OKOYE

2017-11-16

Nov 16, 2017 ... In this work an Adaptive Neuro-Fuzzy Inference System (ANFIS) was used to model the periodic performance of ... Since the .... The investigation hubs are a local brewing company ..... Industrial Engineers, Systems Engineers, Operations ... responsibility the overall management of the new system lies.

Classification of EEG Signals by Radial Neuro-Fuzzy Systems

Czech Academy of Sciences Publication Activity Database

Coufal, David

2006-01-01

Roč. 5, č. 2 (2006), s. 415-423 ISSN 1109-2777 R&D Projects: GA MŠk ME 701 Institutional research plan: CEZ:AV0Z10300504 Keywords : neuro-fuzzy systems * radial fuzzy systems * data mining * hybrid systems Subject RIV: BA - General Mathematics

Global cross-station assessment of neuro-fuzzy models for estimating daily reference evapotranspiration

Science.gov (United States)

Shiri, Jalal; Nazemi, Amir Hossein; Sadraddini, Ali Ashraf; Landeras, Gorka; Kisi, Ozgur; Fard, Ahmad Fakheri; Marti, Pau

2013-02-01

SummaryAccurate estimation of reference evapotranspiration is important for irrigation scheduling, water resources management and planning and other agricultural water management issues. In the present paper, the capabilities of generalized neuro-fuzzy models were evaluated for estimating reference evapotranspiration using two separate sets of weather data from humid and non-humid regions of Spain and Iran. In this way, the data from some weather stations in the Basque Country and Valencia region (Spain) were used for training the neuro-fuzzy models [in humid and non-humid regions, respectively] and subsequently, the data from these regions were pooled to evaluate the generalization capability of a general neuro-fuzzy model in humid and non-humid regions. The developed models were tested in stations of Iran, located in humid and non-humid regions. The obtained results showed the capabilities of generalized neuro-fuzzy model in estimating reference evapotranspiration in different climatic zones. Global GNF models calibrated using both non-humid and humid data were found to successfully estimate ET0 in both non-humid and humid regions of Iran (the lowest MAE values are about 0.23 mm for non-humid Iranian regions and 0.12 mm for humid regions). non-humid GNF models calibrated using non-humid data performed much better than the humid GNF models calibrated using humid data in non-humid region while the humid GNF model gave better estimates in humid region.

Neuro-QOL and the NIH Toolbox: implications for epilepsy

Science.gov (United States)

Nowinski, Cindy J; Victorson, David; Cavazos, Jose E; Gershon, Richard; Cella, David

2011-01-01

The impact of neurological disorders on the lives of patients is often far more complex than what is measured in routine examination. Measurement of this impact can be challenging owing to a lack of brief, psychometrically sound and generally accepted instruments. Two NIH-funded initiatives are developing assessment tools, in English and Spanish, which address these issues, and should prove useful to the study and treatment of epilepsy and other neurological conditions. The first, Neuro-QOL, has created a set of health-related quality of life measures that are applicable for people with common neurological disorders. The second, the NIH Toolbox for the Assessment of Neurological and Behavioral Function, is assembling measures of cognitive, emotional, motor and sensory health and function that can be used across all ages, from 3 to 85 years. This article describes both the projects and their potential value to epilepsy treatment and research. PMID:21552344

The effectiveness of neuro-music therapy according to the Heidelberg model compared to a single session of educational counseling as treatment for tinnitus: a controlled trial.

Science.gov (United States)

Argstatter, Heike; Grapp, Miriam; Hutter, Elisabeth; Plinkert, Peter K; Bolay, Hans-Volker

2015-03-01

Tinnitus is a very common symptom, yet the quest for an effective treatment is challenging. Results from several clinical trials support the notion that neuro-music therapy is an effective means to reduce tinnitus distress with short duration and long lasting effect. However, until now, the effectiveness has not been tested in a controlled trial against an active comparator. The trial was designed as two-center, parallel intervention group controlled study with two intervention groups: Counseling (50minute individualized personal instruction) or neuro-music therapy (counseling plus eight 50-minute sessions of individualized music therapy). Data of n=290 patients suffering from chronic tinnitus were analyzed. Outcome measure was the change in Tinnitus Questionnaire Total Scores (TQ) from baseline (admission) to end of treatment. Both treatment groups achieved a statistically relevant reduction in TQ scores, though 66% of patients in the music therapy group attained a clinically meaningful improvement compared to 33% in the counseling group. A binary logistic regression revealed two variables significantly influencing therapy outcome: initial tinnitus score and type of therapy with an OR for the music therapy compared to the counseling of 4.34 (CI 2.33-8.09). Counseling is an appropriate treatment option with well above chance of improvement. The neuro-music therapy outperformed the counseling. This treatment targets the tinnitus sound itself, is short in duration, intrinsically motivating and easy to operate and thus presents a possible complement to the therapeutic spectrum in chronic tinnitus. The trial was registered at the ClinicalTrials.gov registry (ID: NCT01845155). Copyright © 2014 Elsevier Inc. All rights reserved.

Development and validation of the positive affect and well-being scale for the neurology quality of life (Neuro-QOL) measurement system.

Science.gov (United States)

Salsman, John M; Victorson, David; Choi, Seung W; Peterman, Amy H; Heinemann, Allen W; Nowinski, Cindy; Cella, David

2013-11-01

To develop and validate an item-response theory-based patient-reported outcomes assessment tool of positive affect and well-being (PAW). This is part of a larger NINDS-funded study to develop a health-related quality of life measurement system across major neurological disorders, called Neuro-QOL. Informed by a literature review and qualitative input from clinicians and patients, item pools were created to assess PAW concepts. Items were administered to a general population sample (N = 513) and a group of individuals with a variety of neurologic conditions (N = 581) for calibration and validation purposes, respectively. A 23-item calibrated bank and a 9-item short form of PAW was developed, reflecting components of positive affect, life satisfaction, or an overall sense of purpose and meaning. The Neuro-QOL PAW measure demonstrated sufficient unidimensionality and displayed good internal consistency, test-retest reliability, model fit, convergent and discriminant validity, and responsiveness. The Neuro-QOL PAW measure was designed to aid clinicians and researchers to better evaluate and understand the potential role of positive health processes for individuals with chronic neurological conditions. Further psychometric testing within and between neurological conditions, as well as testing in non-neurologic chronic diseases, will help evaluate the generalizability of this new tool.

Comparative Evaluation of the Translocator Protein Radioligands 11C-DPA-713, 18F-DPA- 714, and 11C-PK11195 in a Rat Model of Acute Neuro-inflammation

International Nuclear Information System (INIS)

Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B.; Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B.; Chauveau, F.; Boutin, H.; James, M.; Kassiou, M.; Kassiou, M.

2009-01-01

Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, 11 C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and 18 F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: 11 C-DPA-713 and 18 F-DPA-714, as well as the classic radioligand 11 C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: 11 C-DPA-713 and 18 F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, 18 F-DPA-714 performed better than 11 C-DPA-713 and 11 C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: 18 F-DPA-714 appears to be an attractive alternative to 11 C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with 18 F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. 18 F-DPA-714 will be further evaluated in longitudinal studies of neuro-inflammatory conditions such as are encountered in stroke or neuro

Rating of intra-operative neuro-monitoring results in operative correction of the spinal deformities

Directory of Open Access Journals (Sweden)

A. A. Skripnikov

2015-01-01

Full Text Available Purpose of the work was filing the electrophysiological phenomena observed in the process of intra-operative neuromonitoring followed by development of the results’ scale of intra-operative neuro-physiological testing of the pyramidal tract. Materials and мethods. The selection for evaluation included data of 147 protocols of intra-operative neuromonitoring in 135 patients (53 males, 82 females, aged from 1 y. 5 m. to 52 years (14,1±0,7 years with spinal deformities of different etiology who underwent instrumentation spinal correction followed by fixation of thoracic / thoracolumbar spine segments using various variants of internal systems of trans-pedicular fixation. Intra-operative neuro-monitoring was performed using system «ISIS IOM» (Inomed Medizintechnik GmbH, Germany. The changes of motor evoked potentials were evaluated according to this scale. Results. Five types of pyramidal system reaction to operative invasion were revealed. According to neurophysiological criteria three grades of the risk of neurological disorders development during operative spinal deformity correction and, correspondingly, three levels of anxiety for the surgeon were defined. Conclusion. Intra-operative neurophysiological monitoring is the effective highly technological instrument to prevent neurological disorders in the spinal deformity. Offered rating scale of the risk of neurological complications gives the possibility to highlight three levels of anxiety during operative invasion.

The role of ATP-binding cassette transporters in neuro-inflammation: relevance for bioactive lipids

Directory of Open Access Journals (Sweden)

Gijs eKooij

2012-04-01

Full Text Available ATP-binding cassette (ABC transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB. These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous system (CNS. Consequently, their high activity at the BBB has been a major hurdle for the treatment of several brain diseases, as they prevent numerous drugs to reach their site of action within the brain. Importantly, recent data indicate that endogenous substrates for ABC transporters may include inflammatory mediators, such as prostaglandins, leukotrienes, cytokines, chemokines and bioactive lipids, suggesting a potential role for ABC transporters in immunological responses, and more specifically in inflammatory brain disorders, such as multiple sclerosis (MS. In this review, we will give a comprehensive overview of recent findings that illustrate this novel role for ABC transporters in neuro-inflammatory processes. Moreover, we will provide first insights into underlying mechanisms and focus on the importance for bioactive lipids, in particular platelet-activating factor (PAF, herein. A thorough understanding of these events may form the basis for the development for selective treatment modalities to dampen the neuro-inflammatory attack in MS and thereby reducing tissue damage.

Planning Future Strategies for Domestic and International NeuroAIDS Research, July 24?25, 2008

OpenAIRE

Joseph, Jeymohan; Clifford, David; Douglas, Steven D.; Fox, Howard; Gendelman, Howard E.; Gonzalez-Scarano, Francisco; Grant, Igor; Major, Eugene; McArthur, Justin

2009-01-01

The National Institute of Mental Health in cooperation with the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke organized a meeting on July 24?25, 2008 to develop novel research directions for neuroAIDS research. The deliberations of this meeting are outlined in this brief report. Several critical research areas in neuroAIDS were identified as areas of emphasis. Opportunities for collaborations between large NIH-funded projects were also discus...

Novel endogenous angiogenesis inhibitors and their therapeutic potential.

Science.gov (United States)

Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

2015-10-01

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application.

Anatomically detailed and large-scale simulations studying synapse loss and synchrony using NeuroBox

Directory of Open Access Journals (Sweden)

Markus eBreit

2016-02-01

Full Text Available The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic or reconstruction to the simulation platform UG 4 (which harbors a neuroscientific portfolio and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g. new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

The Therapeutic Potential of Brown Adipocytes in Humans

Directory of Open Access Journals (Sweden)

Craig ePorter

2015-10-01

Full Text Available Obesity and its metabolic consequences represent a significant clinical problem. From a thermodynamic standpoint, obesity results from a discord in energy intake and expenditure. To date, lifestyle interventions based on reducing energy intake and/or increasing energy expenditure have proved ineffective in the prevention and treatment of obesity, owing to poor long-term adherence to such interventions. Thus, an effective strategy to prevent or correct obesity is currently lacking.As the combustion engines of our cells, mitochondria play a critical role in energy expenditure. At a whole body level, approximately 80% of mitochondrial membrane potential generated by fuel oxidation is used to produce ATP, and the remaining 20% is lost through heat-producing uncoupling reactions. The coupling of mitochondrial respiration to ATP production represents an important component in whole body energy expenditure. Brown adipose tissue (BAT is densely populated with mitochondria containing the inner mitochondrial proton carrier uncoupling protein 1 (UCP. UCP1 uncouples oxidative phosphorylation, meaning that mitochondrial membrane potential is dissipated as heat. The recent re-discovery of BAT depots in adult humans has rekindled scientific interest in the manipulation of mitochondrial uncoupling reactions as a means to increase metabolic rate, thereby counteracting obesity and its associated metabolic phenotype. In this article, we discuss the evidence for the role BAT plays in metabolic rate and glucose and lipid metabolism in humans, and the potential for UCP1 recruitment in the white adipose tissue of humans. While the future holds much promise for a therapeutic role of UCP1 expressing adipocytes in human energy metabolism, particularly in the context of obesity, tissue specific strategies that activate or recruit UCP1 in human adipocytes represent an obligatory translation step for this early promise to be realized.

A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

Directory of Open Access Journals (Sweden)

Yuji Tada

2013-01-01

Full Text Available Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

Kleptomania in patients with neuro-Behçet's disease.

Science.gov (United States)

Shugaiv, Erkingül; Kıyat-Atamer, Aslı; Tüzün, Erdem; Kürtüncü, Murat; Baral-Kulaksızoğlu, Işın; Akman Demir, Gülşen

2013-01-01

This study was conducted to characterize the prevalence and clinical features of kleptomania, an impulse control disorder, in patients with Behçet's disease involving the central nervous system. Medical records of 350 patients with neuro-Behçet's disease were evaluated, and clinical and neuropsychological features of patients with kleptomania were noted. Of the 350 neuro-Behçet's disease patients 6 (1.7%) had presented with symptoms that fulfilled the criteria of kleptomania according to the revised 4th version of the Diagnostic and Statistical Manual of Mental Disorders. The 6 patients (5 men, 1 woman) had parenchymal lesions and had developed kleptomania during remission. Magnetic resonance imaging done on the 6 patients before the onset of kleptomania mostly revealed brainstem lesions. Psychiatric assessment did not show any comorbid psychiatric disorders and neuropsychological evaluation showed executive dysfunction in all patients. The 6 patients with kleptomania had developed a frontal lobe syndrome. Copyright © 2013 S. Karger AG, Basel.

Therapeutic potential of mGluR5 targeting in Alzheimer's disease

Directory of Open Access Journals (Sweden)

Anil eKumar

2015-06-01

Full Text Available Decades of research dedicated towards Alzheimer's disease (AD has culminated in much of the current understanding of the neurodegeneration associated with disease. However, delineating the pathophysiology and finding a possible cure for the disease is still wanting. This is in part due to the lack of knowledge pertaining to the connecting link between neurodegenerative and neuroinflammatory pathways. Consequently, the inefficacy and ill-effects of the drugs currently available for AD encourage the need for alternative and safe therapeutic intervention. In this review we highlight the potential of mGluR5, a metabotropic glutamatergic receptor, in understanding the mechanism underlying the neuronal death and neuroinflammation in AD. We also discuss the role of mGlu5 receptor in mediating the neuron-glia interaction in the disease. Finally, we discuss the potential of mGluR5 as target for treating AD.

Inference of RMR value using fuzzy set theory and neuro-fuzzy techniques

Energy Technology Data Exchange (ETDEWEB)

Bae, Gyu-Jin; Cho, Mahn-Sup [Korea Institute of Construction Technology, Koyang(Korea)

2001-12-31

In the design of tunnel, it contains inaccuracy of data, fuzziness of evaluation, observer error and so on. The face observation during tunnel excavation, therefore, plays an important role to raise stability and to reduce supporting cost. This study is carried out to minimize the subjectiveness of observer and to exactly evaluate the natural properties of ground during the face observation. For these purpose, fuzzy set theory and neuro-fuzzy techniques in artificial intelligent techniques are applied to the inference of the RMR(Rock Mass Rating) value from the observation data. The correlation between original RMR value and inferred RMR{sub {sub F}U} and RMR{sub {sub N}F} values from fuzzy Set theory and neuro-fuzzy techniques is investigated using 46 data. The results show that good correlation between original RMR value and inferred RMR{sub {sub F}U} and RMR{sub {sub N}F} values is observed when the correlation coefficients are |R|=0.96 and |R|=0.95 respectively. >From these results, applicability of fuzzy set theory and neuro-fuzzy techniques to rock mass classification is proved to be sufficiently high enough. (author). 17 refs., 5 tabs., 9 figs.

Vision rehabilitation for visual-vestibular dysfunction: the role of the neuro-optometrist.

Science.gov (United States)

Cohen, Allen H

2013-01-01

This article discusses, in a clinically relevant format, the importance of including a neuro-optometrist as a member of the management team for patients with balance disorders. To review the importance of vision and visual processing for maintaining a sense of balance and equilibrium and the role of the neuro-optometrist in the overall rehabilitation of patients with balance disorders Dizziness, balance problems and the sensation that the space world is moving (vertigo) are one of the most commonly reported problems in general medical practice. Persons with a central nervous system injury or other idiopathic causes of visual processing problems or who have functional vision problems that are not adequately managed, often experience extreme difficulty with balance and movement, as well as with their perception of space. Consequently, the patient often experiences difficulty functioning in an environment with excessive visual stimulation such as a grocery store or shopping mall. Symptoms of disequilibrium, vestibular and balance problems are commonly a result of VOR disturbance secondary to an inner ear problem and an unstable binocularity. The combination of neuro-optomertic rehabilitative therapy and balance therapy will result in a is an effective treatment for reducing or resolving these symptoms.

Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and Dyslipidemia: A Review

Science.gov (United States)

Mbikay, Majambu

2012-01-01

Moringa oleifera (M. oleifera) is an angiosperm plant, native of the Indian subcontinent, where its various parts have been utilized throughout history as food and medicine. It is now cultivated in all tropical and sub-tropical regions of the world. The nutritional, prophylactic, and therapeutic virtues of this plant are being extolled on the Internet. Dietary consumption of its part is therein promoted as a strategy of personal health preservation and self-medication in various diseases. The enthusiasm for the health benefits of M. oleifera is in dire contrast with the scarcity of strong experimental and clinical evidence supporting them. Fortunately, the chasm is slowly being filled. In this article, I review current scientific data on the corrective potential of M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of diabetes and cardiovascular disease (CVD) risk. Reported studies in experimental animals and humans, although limited in number and variable in design, seem concordant in their support for this potential. However, before M. oleifera leaf formulations can be recommended as medication in the prevention or treatment of diabetes and CVD, it is necessary that the scientific basis of their efficacy, the therapeutic modalities of their administration and their possible side effects be more rigorously determined. PMID:22403543

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool.

Science.gov (United States)

Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

2016-01-01

The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo's time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo's time perspective offers both: 1) a potential diagnostic tool - the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.

Therapeutic potential of Moringa oleifera leaves in chronic hyperglycemia and dyslipidemia: a review

Directory of Open Access Journals (Sweden)

Majambu eMbikay

2012-03-01

Full Text Available Moringa oleifera (M. oleifera is an angiosperm plant, native of the Indian subcontinent, where its various parts have been utilized throughout history as food and medicine. It is now cultivated in all tropical and subtropical regions of the world. The nutritional, prophylactic, and therapeutic virtues of this plant are being extolled on the Internet. Dietary consumption of its part is therein promoted as a strategy of personal health preservation and self-medication in various diseases. The enthusiasm for the health benefits of M. oleifera is in dire contrast with the scarcity of strong experimental and clinical evidence supporting them. Fortunately, the chasm is slowly being filled. In this article, I review current scientific data on the corrective potential of M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of diabetes and cardiovascular disease risk. Reported studies in experimental animals and humans, although limited in number and variable in design, seem concordant in their support for this potential. However, before M. oleifera leaf formulations can be recommended as medication in the prevention or treatment of diabetes and cardiovascular disease, it is necessary that the scientific basis of their efficacy, the therapeutic modalities of their administration and their possible side effects be more rigorously determined.

Developed adaptive neuro-fuzzy algorithm to control air conditioning ...

African Journals Online (AJOL)

The paper developed artificial intelligence technique adaptive neuro-fuzzy controller for air conditioning systems at different pressures. The first order Sugeno fuzzy inference system was implemented and utilized for modeling and controller design. In addition, the estimation of the heat transfer rate and water mass flow rate ...

Developed adaptive neuro-fuzzy algorithm to control air conditioning ...

African Journals Online (AJOL)

user

The paper developed artificial intelligence technique adaptive neuro-fuzzy ... system is highly appreciated and essential in most of our daily life. ... It can construct an input-output mapping based on human knowledge and specific input-output data ... fuzzy controllers to produce desirable internal temperature and air quality, ...

The chicken TH1 response: potential therapeutic applications of ChIFN-γ.

Science.gov (United States)

Guo, Pengju; Thomas, Jesse D; Bruce, Matthew P; Hinton, Tracey M; Bean, Andrew G D; Lowenthal, John W

2013-11-01

The outcomes of viral infections are costly in terms of human and animal health and welfare worldwide. The observed increase in the virulence of some viruses and failure of many vaccines to stop these infections has lead to the apparent need to develop new anti-viral strategies. One approach to dealing with viral infection may be to employ the therapeutic administration of recombinant cytokines to act as 'immune boosters' to assist in augmenting the host response to virus. With this in mind, a greater understanding of the immune response, particularly cell mediated T-helper-1 (TH1) type responses, is imperative to the development of new anti-viral and vaccination strategies. Following the release of the chicken genome, a number of TH1-type cytokines have been identified, including chicken interleukin-12 (ChIL-12), ChIL-18 and interferon-γ ChIFN-γ), highlighting the nature of the TH1-type response in this non-mammalian vertebrate. To date a detailed analysis of the in vivo biological function of these cytokines has been somewhat hampered by access to large scale production techniques. This review describes the role of TH-1 cytokines in immune responses to viruses and explores their potential use in enhancing anti-viral treatment strategies in chickens. Furthermore, this review focuses on the example of ChIFN-γ treatment of Chicken Anemia Virus (CAV) infection. CAV causes amongst other things thymocyte depletion and thymus atrophy, as well as immunosuppression in chickens. However, due to vaccination, clinical disease appears less often, nevertheless, the subclinical form of the disease is often associated with secondary complicating infections due to an immunocompromised state. Since CAV-induced immunosuppression can cause a marked decrease in the immune response against other pathogens, understanding this aspect of the disease is critically important, as well as providing insights into developing new control approaches. With increasing emphasis on developing

Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics

Science.gov (United States)

Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.

2018-01-01

The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.

Music Therapy Advances in Neuro-disability - Innovations in Research and Practice

DEFF Research Database (Denmark)

O'Kelly, Julian; Magee, Wendy L.; Street, Alex

2014-01-01

therapy, music neuroscience and music psychology addressing the needs of those with acquired and degenerative neurological conditions. The diverse and evolving work in this field is reflected in the topics covered, including disorders of consciousness, dementia, stroke, and the use of modern neuro......-imaging methods to measure the effects of music therapy at a cortical level. A discussion of the implications of these converging foci highlights the benefits of the cross-disciplinary dialogue that characterised the conference.......This article provides a summary of the oral papers presented during a two day international conference, which took place on 7th & 8th June 2013, at the Royal Hospital for Neuro-disability (RHN) in London. The summary texts detail innovative research projects and clinical developments across music...

Isolation of two tissue-specific Drosophila paired box genes, Pox meso and Pox neuro.

OpenAIRE

Bopp, D; Jamet, E; Baumgartner, S; Burri, M; Noll, M

1989-01-01

Two new paired domain genes of Drosophila, Pox meso and Pox neuro, are described. In contrast to the previously isolated paired domain genes, paired and gooseberry, which contain both a paired and a homeo-domain (PHox genes), Pox meso and Pox neuro possess no homeodomain. Evidence suggesting that the new genes encode tissue-specific transcriptional factors and belong to the same regulatory cascade as the other paired domain genes includes (i) tissue-specific expression of Pox meso in the soma...

Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2014-04-01

Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

Directory of Open Access Journals (Sweden)

Go Makimoto

2012-02-01

Full Text Available We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR, magnetic resonance imaging (MRI and diffusion-weighted images (DWI showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions.

Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

Directory of Open Access Journals (Sweden)

Ming-Ming Tsai

2016-06-01

Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy.

Science.gov (United States)

Cao, Qi; Wang, Yiping; Wang, Changqi; Wang, Xin M; Lee, Vincent W S; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

2018-04-01

Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.

[A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

Science.gov (United States)

Nakano, Yuko; Hatanaka, Yuki; Ikebuchi, Emi; Shimizu, Teruo; Nanko, Shinichiro; Utsumii, Takeshi

2004-01-01

In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

La frequence des affections neuro-ophtalmologiques au CHU ...

African Journals Online (AJOL)

But: faire une description clinique des affections neuro-ophtalmologiques et déterminer la fréquence de ces pathologies. Méthodologie: Il s'agit d'une étude prospective menée sur une année dans le service d'ophtalmologie du CHU Sylvanus Olympio de Lomé. Etaient inclus tous cas suspect de baisse d'acuité visuelle ...

Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

Science.gov (United States)

Irwin, Nigel; Gault, Victor; Flatt, Peter R

2010-09-01

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

Validity Evidence for the Neuro-Endoscopic Ventriculostomy Assessment Tool (NEVAT)

NARCIS (Netherlands)

Breimer, Gerben E.; Haji, Faizal A.; Cinalli, Giuseppe; Hoving, Eelco W.; Drake, James M.

BACKGROUND: Growing demand for transparent and standardized methods for evaluating surgical competence prompted the construction of the Neuro-Endoscopic Ventriculostomy Assessment Tool (NEVAT). OBJECTIVE: To provide validity evidence of the NEVAT by reporting on the tool's internal structure and its

Neuro-Inspired Computing with Stochastic Electronics

KAUST Repository

Naous, Rawan

2016-01-06

The extensive scaling and integration within electronic systems have set the standards for what is addressed to as stochastic electronics. The individual components are increasingly diverting away from their reliable behavior and producing un-deterministic outputs. This stochastic operation highly mimics the biological medium within the brain. Hence, building on the inherent variability, particularly within novel non-volatile memory technologies, paves the way for unconventional neuromorphic designs. Neuro-inspired networks with brain-like structures of neurons and synapses allow for computations and levels of learning for diverse recognition tasks and applications.

An efficient Neuro-Fuzzy approach to nuclear power plant transient identification

Energy Technology Data Exchange (ETDEWEB)

Gomes da Costa, Rafael [Instituto de Engenharia Nuclear - CNEN, Programa de Pos-Graduacao em Ciencia e Tecnologia Nucleares, Via Cinco, s/no, Cidade Universitaria, Rua Helio de Almeida, 75, Postal Box 68550, Zip Code 21941-906 Rio de Janeiro (Brazil); Abreu Mol, Antonio Carlos de, E-mail: mol@ien.gov.br [Instituto de Engenharia Nuclear - CNEN, Programa de Pos-Graduacao em Ciencia e Tecnologia Nucleares, Via Cinco, s/no, Cidade Universitaria, Rua Helio de Almeida, 75, Postal Box 68550, Zip Code 21941-906 Rio de Janeiro (Brazil); Instituto Nacional de C and T de Reatores Nucleares Inovadores (Brazil); Carvalho, Paulo Victor R. de, E-mail: paulov@ien.gov.br [Instituto de Engenharia Nuclear - CNEN, Programa de Pos-Graduacao em Ciencia e Tecnologia Nucleares, Via Cinco, s/no, Cidade Universitaria, Rua Helio de Almeida, 75, Postal Box 68550, Zip Code 21941-906 Rio de Janeiro (Brazil); Lapa, Celso Marcelo Franklin, E-mail: lapa@ien.gov.br [Instituto de Engenharia Nuclear - CNEN, Programa de Pos-Graduacao em Ciencia e Tecnologia Nucleares, Via Cinco, s/no, Cidade Universitaria, Rua Helio de Almeida, 75, Postal Box 68550, Zip Code 21941-906 Rio de Janeiro (Brazil); Instituto Nacional de C and T de Reatores Nucleares Inovadores (Brazil)

2011-06-15

Highlights: > We investigate a Neuro-Fuzzy modeling tool use for able transient identification. > The prelusive transient type identification is done by an artificial neural network. > After, the fuzzy-logic system analyzes the results emitting reliability degree of it. > The research support was made in a PWR simulator at the Brazilian Nuclear Engineering Institute. > The results show the potential to help operators' decisions in a nuclear power plant. - Abstract: Transient identification in nuclear power plants (NPP) is often a computational very hard task and may involve a great amount of human cognition. The early identification of unexpected departures from steady state behavior is an essential step for the operation, control and accident management in NPPs. The bases for the transient identification relay on the evidence that different system faults and anomalies lead to different pattern evolution in the involved process variables. During an abnormal event, the operator must monitor a great amount of information from the instruments that represents a specific type of event. Recently, several works have been developed for transient identification. These works frequently present a non reliable response, using the 'don't know' as the system output. In this work, we investigate the possibility of using a Neuro-Fuzzy modeling tool for efficient transient identification, aiming to helping the operator crew to take decisions relative to the procedure to be followed in situations of accidents/transients at NPPs. The proposed system uses artificial neural networks (ANN) as first level transient diagnostic. After the ANN has done the preliminary transient type identification, a fuzzy-logic system analyzes the results emitting reliability degree of it. A validation of this identification system was made at the three loops Pressurized Water Reactor (PWR) simulator of the Human-System Interface Laboratory (LABIHS) of the Nuclear Engineering Institute

An efficient Neuro-Fuzzy approach to nuclear power plant transient identification

International Nuclear Information System (INIS)

Gomes da Costa, Rafael; Abreu Mol, Antonio Carlos de; Carvalho, Paulo Victor R. de; Lapa, Celso Marcelo Franklin

2011-01-01

Highlights: → We investigate a Neuro-Fuzzy modeling tool use for able transient identification. → The prelusive transient type identification is done by an artificial neural network. → After, the fuzzy-logic system analyzes the results emitting reliability degree of it. → The research support was made in a PWR simulator at the Brazilian Nuclear Engineering Institute. → The results show the potential to help operators' decisions in a nuclear power plant. - Abstract: Transient identification in nuclear power plants (NPP) is often a computational very hard task and may involve a great amount of human cognition. The early identification of unexpected departures from steady state behavior is an essential step for the operation, control and accident management in NPPs. The bases for the transient identification relay on the evidence that different system faults and anomalies lead to different pattern evolution in the involved process variables. During an abnormal event, the operator must monitor a great amount of information from the instruments that represents a specific type of event. Recently, several works have been developed for transient identification. These works frequently present a non reliable response, using the 'don't know' as the system output. In this work, we investigate the possibility of using a Neuro-Fuzzy modeling tool for efficient transient identification, aiming to helping the operator crew to take decisions relative to the procedure to be followed in situations of accidents/transients at NPPs. The proposed system uses artificial neural networks (ANN) as first level transient diagnostic. After the ANN has done the preliminary transient type identification, a fuzzy-logic system analyzes the results emitting reliability degree of it. A validation of this identification system was made at the three loops Pressurized Water Reactor (PWR) simulator of the Human-System Interface Laboratory (LABIHS) of the Nuclear Engineering Institute (IEN

Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent

Directory of Open Access Journals (Sweden)

Der Jiun Ooi

2016-06-01

Full Text Available Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF isolated from M. latifolia rhizome methanolic extract (RME contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

Science.gov (United States)

Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

2012-08-01

As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological Malignancy.

Science.gov (United States)

Franzen, Carrie A; Blackwell, Robert H; Foreman, Kimberly E; Kuo, Paul C; Flanigan, Robert C; Gupta, Gopal N

2016-05-01

Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer. We searched PubMed® and Google® with the key words prostate cancer, bladder cancer, kidney cancer, exosomes, microvesicles and urine. Relevant articles, including original research studies and reviews, were selected based on contents. A review of this literature was generated. Cancer exosomes can be isolated from urine using various techniques. Cancer cells have been found to secrete more exosomes than normal cells. These exosomes have a role in cellular communication by interacting with and depositing their cargo in target cells. Bladder, prostate and renal cancer exosomes have been shown to enhance migration, invasion and angiogenesis. These exosomes have also been shown to increase proliferation, confer drug resistance and promote immune evasion. Urinary exosomes can be isolated from bladder, kidney and prostate cancer. They serve as a potential reservoir for biomarker identification. Exosomes also have potential for therapeutics as siRNA or pharmacological agents can be loaded into exosomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells

International Nuclear Information System (INIS)

He Mindi; Xu Shangcheng; Lu Yonghui; Li Li; Zhong Min; Zhang Yanwen; Wang Yuan; Li Min; Yang Ju; Zhang Guangbin; Yu Zhengping; Zhou Zhou

2011-01-01

Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl 2 ) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl 2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ m ), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.

Adaptive Neuro-Fuzzy Computing Technique for Determining Turbulent Flow Friction Coefficient

Directory of Open Access Journals (Sweden)

Mohammad Givehchi

2013-08-01

Full Text Available Estimation of the friction coefficient in pipes is very important in many water and wastewater engineering issues, such as distribution of velocity and shear stress, erosion, sediment transport and head loss. In analyzing these problems, knowing the friction coefficient, can obtain estimates that are more accurate. In this study in order to estimate the friction coefficient in pipes, using adaptive neuro-fuzzy inference systems (ANFIS, grid partition method was used. For training and testing of neuro-fuzzy model, the data derived from the Colebrook’s equation was used. In the neuro-fuzzy approach, pipe relative roughness and Reynolds number are considered as input variables and friction coefficient as output variable is considered. Performance of the proposed approach was evaluated by using of the data obtained from the Colebrook’s equation and based on statistical indicators such as coefficient determination (R2, root mean squared error (RMSE and mean absolute error (MAE. The results showed that the adaptive nerou-fuzzy inference system with grid partition method and gauss model as an input membership function and linear as an output function could estimate friction coefficient more accurately than other conditions. The new proposed approach in this paper has capability of application in the practical design issues and can be combined with mathematical and numerical models of sediment transfer or real-time updating of these models.

Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

Science.gov (United States)

Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

2006-11-01

Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

Neuro-fuzzy control of structures using acceleration feedback

Science.gov (United States)

Schurter, Kyle C.; Roschke, Paul N.

2001-08-01

This paper described a new approach for the reduction of environmentally induced vibration in constructed facilities by way of a neuro-fuzzy technique. The new control technique is presented and tested in a numerical study that involves two types of building models. The energy of each building is dissipated through magnetorheological (MR) dampers whose damping properties are continuously updated by a fuzzy controller. This semi-active control scheme relies on the development of a correlation between the accelerations of the building (controller input) and the voltage applied to the MR damper (controller output). This correlation forms the basis for the development of an intelligent neuro-fuzzy control strategy. To establish a context for assessing the effectiveness of the semi-active control scheme, responses to earthquake excitation are compared with passive strategies that have similar authority for control. According to numerical simulation, MR dampers are less effective control mechanisms than passive dampers with respect to a single degree of freedom (DOF) building model. On the other hand, MR dampers are predicted to be superior when used with multiple DOF structures for reduction of lateral acceleration.

NEURO-SYSTEM OF AIMING AND STABILIZING WITH A REGULATOR ON THE BASIS OF STANDARD MODEL MODEL REFERENCE CONTROLLER

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B.I. Kuznetsov

2015-08-01

Full Text Available The aim of this work is the synthesis of neural network aiming and stabilization system for the special equipment of moving objects with neuro-controller on the basis of standard model and performance comparison of the neural network system with the neural network predictive control. Build a block diagram of the neural network aiming and stabilization system, based on the subject control principle with PD-regulator in the position loop and with neuro-controller on the basis of standard model in the in the velocity loop. The neuro-controller on the basis of standard model Model Reference Controller is synthesized in the MATLAB Neural Network Toolbox and system simulation is performed. The studies show that the transient state variables of the system are oscillatory. Therefore, the neuro-controller with the prediction NN Predictive Controller should be used for aiming and stabilizing system to provide high dynamic characteristics achieved at the cost of higher complexity and computational cost.

Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

NARCIS (Netherlands)

Heikens, J.; Michiels, E. M.; Behrendt, H.; Endert, E.; Bakker, P. J.; Fliers, E.

1998-01-01

The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25

The human gut microbiota and virome: Potential therapeutic implications.

Science.gov (United States)

Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

2015-12-01

Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Potential therapeutic gain from using p(66)/Be neutrons

International Nuclear Information System (INIS)

Slabbert, J.P.; Jones, D.T.L.; Theron, C.; Serafin, A.; Bohm, L.; Schmitt, G.

1997-01-01

Neutron therapy will be beneficial to patients with tumor types which are resistant to photons but relatively sensitive to high-LET radiation. In this work 15 different cell types, mostly of human tumor decent, were exposed in vitro to 60 Co γ-rays and p(66)/Be neutrons. Micronuclei frequencies in bi-nucleated cells and surviving fractions were determined for each cell type. Following exposure to either 1 or 1.5 Gy neutrons, micronuclei frequencies were significantly correlated with that observed from 2 Gy photons. A strong correlation between mean inactivation doses determined for these radiation modalities from survival curve inactivation parameters, was also noted. In spite of this a significant correlation between the variation in neutron RBE values and photon resistance was established. It is concluded that although neutron and photo sensitivities are related in the group of cell types studies, the use of this high energy neutron source may constitute a potential therapeutic gain for some tumor types. (authors)

Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

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Hong-Jhang Chen

Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

Hepato- and neuro-protective influences of biopropolis on thioacetamide-induced acute hepatic encephalopathy in rats.

Science.gov (United States)

Mostafa, Rasha E; Salama, Abeer A A; Abdel-Rahman, Rehab F; Ogaly, Hanan A

2017-05-01

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of HE were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato- and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, biopropolis, at a dose of 200 mg/kg per day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.

Neuro-Behcet's disease: initial and follow-up MR imaging findings

International Nuclear Information System (INIS)

Kim, Chan Sung; Choi, Sun Seob; Lee, Ha Jong; Ha, Dong Ho; Lee, Yong Il

1998-01-01

The purpose of this study was to evaluate initial and follow-up MR imaging(MRI) findings of neuro-Behcet's disease. MRI of seven clinically diagnosed cases of neuro-Behcet's disease were retrospectively analysed in terms of involved site, pattern, signal intensity, contrast enhancement pattern and changes seen on follow-up. Using a 0.35T or 1.0T unit T2-and T1-weighted spin-echocontrast-enhanced images were obtained in six patients. Follow-up MRI after steroid therapy lastion between two weeks and 16 months was performed in six patients. Lesions involved the midbrain(6/7), pons(5/7), thalamus(4/7), medulla oblongata(3/7), tegmentum(3/7), internal capsule(3/7), middle cerebellar peduncle(2/7), dentate nucleus(1/7), basal ganglia(1/7) and temporal lobe(1/7). They were 1-3cm in size, and their shape was ill-defined and patchy. Inhomogeneous high and low signal-intensity was seen on T2-weighted and T1-weighted images, respectively. In two of six cases there was focal mild patchy enhancement. Euring follow-up lasting for between two weeks and 16 months after steroid therapy, the lesions decreased in extent(n=3D5) or disappeared(n=3D1), and in the brainstem, focal brain atrophy occurred in three cases. Although MRI findings of neuro-Behcet's disease are nonspecific, common involvement of the brainstem, tegmentum and internal capsule, as well as improvement on follow-up MRI, may be helpful diagnostic indicators of this condition.=20

[Functional neuro-navigation and intraoperative magnetic resonance imaging for the resection of gliomas involving eloquent language structures].

Science.gov (United States)

Chen, Xiao-lei; Xu, Bai-nan; Wang, Fei; Meng, Xiang-hui; Zhang, Jun; Jiang, Jin-li; Yu, Xin-guang; Zhou, Ding-biao

2011-08-01

To explore the clinical value of functional neuro-navigation and high-field-strength intraoperative magnetic resonance imaging (iMRI) for the resection of intracerebral gliomas involving eloquent language structures. From April 2009 to April 2010, 48 patients with intracerebral gliomas involving eloquent language structures, were operated with functional neuro-navigation and iMRI. Blood oxygen level dependent functional MRI (BOLD-fMRI) was used to depict both Broca and Wernicke cortex, while diffusion tensor imaging (DTI) based fiber tracking was used to delineate arcuate fasciculus. The reconstructed language structures were integrated into a navigation system, so that intra-operative microscopic-based functional neuro-navigation could be achieved. iMRI was used to update the images for both language structures and residual tumors. All patients were evaluated for language function pre-operatively and post-operatively upon short-term and long-term follow-up. In all patients, functional neuro-navigation and iMRI were successfully achieved. In 38 cases (79.2%), gross total resection was accomplished, while in the rest 10 cases (20.8%), subtotal resection was achieved. Only 1 case (2.1%) developed long-term (more than 3 months) new language function deficits at post-operative follow-up. No peri-operative mortality was recorded. With functional neuro-navigation and iMRI, the eloquent structures for language can be precisely located, while the resection size can be accurately evaluated intra-operatively. This technique is safe and helpful for preservation of language function.

Amyloid-β peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.

Science.gov (United States)

Hanenberg, Michael; McAfoose, Jordan; Kulic, Luka; Welt, Tobias; Wirth, Fabian; Parizek, Petra; Strobel, Lisa; Cattepoel, Susann; Späni, Claudia; Derungs, Rebecca; Maier, Marcel; Plückthun, Andreas; Nitsch, Roger M

2014-09-26

Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Therapeutic potential of bryophytes and derived compounds against cancer

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Abhijit Dey

2015-08-01

Full Text Available Bryophytes, taxonomically placed between the algae and the pteridophytes, are divided into three classes such as Liverworts, Hornworts and Mosses. Indigenous use involves this small group of plants to treat various diseases. Bryophytes have been investigated pharmacologically for active biomolecules. Several constituents with therapeutic potential have been isolated, characterized and investigated for antibacterial, antifungal, antiviral, antioxidative, antiinflamatory and anticancerous efficacy. The present review deals with the literature covering the anticancerous potential of bryophytes. Apart from the examples of the compounds and the containing bryophyte genera, the authors have tried to include the examples of cancer cell lines on which the efficacy have been tested and the mode of action of certain cytotoxic agents. Crude extracts and isolated compounds from bryophytes were found to possess potent cytotoxic properties. Different types of terpenoids and bibenzyls have been reported among the most potent cytotoxic compounds. Most of these compounds were found to induce apoptosis by activating a number of genes and enzymes. Biochemical markers such as DNA fragmentation, nuclear condensation, proteolysis of poly (ADP-ribose polymerase, activation of caspases, inhibition of antiapoptotic nuclear transcriptional factor-kappaB, activation of p38 mitogen-activated protein kinase etc. have been found to be associated with apoptotic and necrotic response. This review summarizes recent scientific findings and suggests further investigations to evaluate the cytotoxic efficacy of bryophytes.

ALGORITAMSKA I HEURISTIČKA OBRADA LEKSIČKIH PODATAKA U RAČUNALNOM PREVODIOCU NeuroTran

OpenAIRE

Končar, Nenad; Šipka, Danko

1998-01-01

Obrada leksičkih podataka (u najširem mogućem značenju tog termina) u računalnom prevodiocu NeuroTran vrši se na osnovi pravila pod nazivom gramatika minimalne informacije (skraceno MIG, po engleskoj skraćenici za Minimal Information Grammar). Tri ideje u osnovi su programa NeuroTran i MIG-a. Prva postulira da treba minimalizirati informaciju potrebnu programu da radi, a da nove informacije program treba usvajati čitajući tekstove i komunicirajući s korisnicima, koristeći pri tom neuronske mr...

L'aspergillome sphenoïdal : a propos d'un cas ...

African Journals Online (AJOL)

Objective : Isolated sphenoidalaspergillosis is rare but potentially grave because of the risk of neuro-meningeal and orbitalextension. althoughitis more common in immuno-compromised, the achievement of immunocompetent has been described. Through an observation, we report the clinic-radiological, therapeutic and ...

NeuroLex.org: An online framework for neuroscience knowledge

Directory of Open Access Journals (Sweden)

Stephen D Larson

2013-08-01

Full Text Available The ability to transmit, organize, and query information digitally has brought with it the challenge of how to best use this power to facilitate scientific inquiry. Today, few information systems are able to provide detailed answers to complex questions about neuroscience that account for multiple spatial scales, and which cross the boundaries of diverse parts of the nervous system such as molecules, cellular parts, cells, circuits, systems and tissues. As a result, investigators still primarily seek answers to their questions in an increasingly densely populated collection of articles in the literature, each of which must be digested individually. If it were easier to search a knowledge base that was structured to answer neuroscience questions, such a system would enable questions to be answered in seconds that would otherwise require hours of literature review.In this article, we describe NeuroLex.org, a wiki-based website and knowledge management system. Its goal is to bring neurobiological knowledge into a framework that allows neuroscientists to review the concepts of neuroscience, with an emphasis on multiscale descriptions of the parts of nervous systems, aggregate their understanding with that of other scientists, link them to data sources and descriptions of important concepts in neuroscience, and expose parts that are still controversial or missing. To date, the site is tracking ~25,000 unique neuroanatomical parts and concepts in neurobiology spanning experimental techniques, behavioral paradigms, anatomical nomenclature, genes, proteins and molecules. Here we show how the structuring of information about these anatomical parts in the nervous system can be reused to answer multiple neuroscience questions, such as displaying all known GABAergic neurons aggregated in NeuroLex or displaying all brain regions that are known within NeuroLex to send axons into the cerebellar cortex.

NeuroLex.org: an online framework for neuroscience knowledge

Science.gov (United States)

Larson, Stephen D.; Martone, Maryann E.

2013-01-01

The ability to transmit, organize, and query information digitally has brought with it the challenge of how to best use this power to facilitate scientific inquiry. Today, few information systems are able to provide detailed answers to complex questions about neuroscience that account for multiple spatial scales, and which cross the boundaries of diverse parts of the nervous system such as molecules, cellular parts, cells, circuits, systems and tissues. As a result, investigators still primarily seek answers to their questions in an increasingly densely populated collection of articles in the literature, each of which must be digested individually. If it were easier to search a knowledge base that was structured to answer neuroscience questions, such a system would enable questions to be answered in seconds that would otherwise require hours of literature review. In this article, we describe NeuroLex.org, a wiki-based website and knowledge management system. Its goal is to bring neurobiological knowledge into a framework that allows neuroscientists to review the concepts of neuroscience, with an emphasis on multiscale descriptions of the parts of nervous systems, aggregate their understanding with that of other scientists, link them to data sources and descriptions of important concepts in neuroscience, and expose parts that are still controversial or missing. To date, the site is tracking ~25,000 unique neuroanatomical parts and concepts in neurobiology spanning experimental techniques, behavioral paradigms, anatomical nomenclature, genes, proteins and molecules. Here we show how the structuring of information about these anatomical parts in the nervous system can be reused to answer multiple neuroscience questions, such as displaying all known GABAergic neurons aggregated in NeuroLex or displaying all brain regions that are known within NeuroLex to send axons into the cerebellar cortex. PMID:24009581

Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters

Science.gov (United States)

Writer, Jeffrey; Ferrer, Imma; Barber, Larry B.; Thurman, E. Michael

2013-01-01

Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations ± standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700 ± 1000 ng L−1, 2100 ± 1700 ng L−1, carbamazepine and 10-hydroxy-carbamazepine 480 ± 380 ng L−1, 360 ± 400 ng L−1, venlafaxine and O-desmethyl-venlafaxine 1400 ± 1300 ng L−1, 1800 ± 2300 ng L−1. Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that

Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes.

Science.gov (United States)

Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T

2015-01-01

Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

Survivin-T34A: molecular mechanism and therapeutic potential

Directory of Open Access Journals (Sweden)

Jonathan R Aspe

2010-12-01

Full Text Available Jonathan R Aspe, Nathan R WallCenter for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USAAbstract: The inhibitor of apoptosis protein survivin's threonine 34 to alanine (T34A mutation abolishes a phosphorylation site for p34(cdc2–cyclin B1, resulting in initiation of the mitochondrial apoptotic pathway in cancer cells; however, it has little known direct effects on normal cells. The possibility that targeting survivin in this way may provide a novel approach for selective cancer gene therapy has yet to be fully evaluated. Although a flurry of work was undertaken in the late 1990s and early 2000s, only minor advances on this mutant have recently taken place. We recently described that cells generated to express a stable form of the mutant protein released this survivin-T34A to the conditioned medium. When this conditioned medium was collected and deposited on naive tumor cells, conditioned medium T34A was as effective as some chemotherapeutics in the induction of tumor cell apoptosis, and when combined with other forms of genotoxic stressors potentiated their killing effects. We hope with this review to revitalize the T34A field, as there is still much that needs to be investigated. In addition to determining the therapeutic dose and the duration of drug therapy required at the disease site, a better understanding of other key factors is also important. These include knowledge of target cell populations, cell-surface receptors, changes that occur in the target tissue at the molecular and cellular level with progression of the disease, and the mechanism and site of therapeutic action.Keywords: survivin, T34A, apoptosis, proliferation, therapy

[Patient-centered care. Improvement of communication between university medical centers and general practitioners for patients in neuro-oncology].

Science.gov (United States)

Renovanz, M; Keric, N; Richter, C; Gutenberg, A; Giese, A

2015-12-01

Communication between university medical centers and general practitioners (GP) is becoming increasingly more important in supportive patient care. A survey among GPs was performed with the primary objective to assess their opinion on current workflow and communication between GPs and the university medical center. The GPs were asked to score (grades 1-6) their opinion on the current interdisciplinary workflow in the care of patients with brain tumors, thereby rating communication between a university medical center in general and the neuro-oncology outpatient center in particular. Questionnaires were sent to1000 GPs and the response rate was 15 %. The mean scored evaluation of the university medical center in general was 2.62 and of the neuro-oncological outpatient clinic 2.28 (range 1-6). The most often mentioned issues to be improved were easier/early telephone information (44 %) and a constantly available contact person (49 %). Interestingly, > 60 % of the GPs indicated they would support web-based tumor boards for interdisciplinary and palliative neuro-oncological care. As interdisciplinary care for neuro-oncology patients is an essential part of therapy, improvement of communication between GPs and university medical centers is indispensable. Integrating currently available electronic platforms under data protection aspects into neuro-oncological palliative care could be an interesting tool in order to establish healthcare networks and could find acceptance with GPs.

The Potential for Emerging Microbiome-Mediated Therapeutics in Asthma.

Science.gov (United States)

Ozturk, Ayse Bilge; Turturice, Benjamin Arthur; Perkins, David L; Finn, Patricia W

2017-08-10

In terms of immune regulating functions, analysis of the microbiome has led the development of therapeutic strategies that may be applicable to asthma management. This review summarizes the current literature on the gut and lung microbiota in asthma pathogenesis with a focus on the roles of innate molecules and new microbiome-mediated therapeutics. Recent clinical and basic studies to date have identified several possible therapeutics that can target innate immunity and the microbiota in asthma. Some of these drugs have shown beneficial effects in the treatment of certain asthma phenotypes and for protection against asthma during early life. Current clinical evidence does not support the use of these therapies for effective treatment of asthma. The integration of the data regarding microbiota with technologic advances, such as next generation sequencing and omics offers promise. Combining comprehensive bioinformatics, new molecules and approaches may shape future asthma treatment.

Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.

Science.gov (United States)

Sartawi, Ziad; Schipani, Ernestina; Ryan, Katie B; Waeber, Christian

2017-11-01

The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

Energy Technology Data Exchange (ETDEWEB)

Thonel, Aurelie de [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); Mezger, Valerie, E-mail: valerie.mezger@univ-paris-diderot.fr [CNRS, UMR7216 Epigenetics and Cell Fate, Paris (France); University Paris Diderot, 75013 Paris (France); Garrido, Carmen, E-mail: valerie.mezger@univ-paris-diderot.fr [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); CHU, Dijon BP1542, Dijon (France)

2011-03-07

Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

International Nuclear Information System (INIS)

Thonel, Aurelie de; Mezger, Valerie; Garrido, Carmen

2011-01-01

Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents

Impact of provider level, training and gender on the utilization of palliative care and hospice in neuro-oncology: a North-American survey.

Science.gov (United States)

Walbert, Tobias; Glantz, Michael; Schultz, Lonni; Puduvalli, Vinay K

2016-01-01

Specialized palliative care (PC) services have emerged to address symptoms and provide end-of-life management for patients with brain tumors. The utilization patterns of PC in neuro-oncology are unknown. A 22-question survey was distributed to participants of the society for neuro-oncology annual meeting 2012 (n = 4487). Nonparametric methods including Wilcoxon two-sample and Kruskal-Wallis tests were used to assess differences in responses. 239 (5.3 %) evaluable responses were received; 79 % of respondents were physicians, and 17 % were nurses or midlevel providers. Forty-seven percent were medical or neuro-oncologists, 31 % neurosurgeons and 11 % radiation oncologists. Forty percent had no formal training in PC, 57 % had some formal training and 3 % completed a PC fellowship. Seventy-nine percent practiced in an academic setting. Of the respondents, 57 % referred patients to PC when symptoms required treatment and 18 % at end of life. Only 51 % of all providers felt comfortable dealing with end-of-life issues and symptoms, while 33 % did not. Fifty-one percent preferred a service named "Supportive Care" rather than "Palliative Care" (MDs > midlevel providers, p training in neuro-oncology and PC, and medical versus surgical neuro-oncology training were significantly associated with hospice referral, comfort in dealing with end-of-life issues, and ease of access to PC services. Provider level, specialty, gender, training in PC and neuro-oncology have significant impact on the utilization of PC and hospice in neuro-oncology.

Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics.

Science.gov (United States)

de Lange, Elizabeth C M; van den Brink, Willem; Yamamoto, Yumi; de Witte, Wilhelmus E A; Wong, Yin Cheong

2017-12-01

CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed. Expert opinion: Understanding time- and condition dependent interrelationships between neuro-PK and neuro-PD processes is key to predictions in different conditions. As a first screen, it is suggested to use in silico/in vitro derived molecular properties of candidate compounds and predict concentration-time profiles of compounds in multiple compartments of the human CNS, using time-course based physiology-based (PB) PK models. Then, for selected compounds, one can include in vitro drug-target binding kinetics to predict target occupancy (TO)-time profiles in humans. This will improve neuro-PD prediction. Furthermore, a pharmaco-omics approach is suggested, providing multilevel and paralleled data on systems processes from individuals in a systems-wide manner. Thus, clinical trials will be better informed, using fewer animals, while also, needing fewer individuals and samples per individual for proof of concept in humans.

Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity

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Luc Van Kaer

2018-03-01

Full Text Available Tolerance against self-antigens is regulated by a variety of cell types with immunoregulatory properties, such as CD1d-restricted invariant natural killer T (iNKT cells. In many experimental models of autoimmunity, iNKT cells promote self-tolerance and protect against autoimmunity. These findings are supported by studies with patients suffering from autoimmune diseases. Based on these studies, the therapeutic potential of iNKT cells in autoimmunity has been explored. Many of these studies have been performed with the potent iNKT cell agonist KRN7000 or its structural variants. These findings have generated promising results in several autoimmune diseases, although mechanisms by which iNKT cells modulate autoimmunity remain incompletely understood. Here, we will review these preclinical studies and discuss the prospects for translating their findings to patients suffering from autoimmune diseases.

Emerging therapeutic potential for xenin and related peptides in obesity and diabetes.

Science.gov (United States)

Craig, Sarah L; Gault, Victor A; Irwin, Nigel

2018-04-06

Xenin-25 is a 25 amino acid peptide hormone co-secreted from the same enteroendocrine K-cell as the incretin peptide glucose-dependent insulinotropic polypeptide (GIP). There is no known specific receptor for xenin-25, but studies suggest that at least some biological actions may be mediated through interaction with the neurotensin receptor. Original investigation into the physiological significance of xenin-25 focussed on effects related to gastrointestinal transit and satiety. However, xenin-25 has been demonstrated in pancreatic islets and recently shown to possess actions in relation to the regulation of insulin and glucagon secretion, as well as promoting beta-cell survival. Accordingly, the beneficial impact of xenin-25, and related analogues, has been assessed in animal models of diabetes-obesity. In addition, studies have demonstrated that metabolically active fragment peptides of xenin-25, particularly xenin-8, possess independent therapeutic promise for diabetes, as well as serving as bioactive components for the generation of multi-acting hybrid peptides with antidiabetic potential. This review will focus on continuing developments with xenin compounds in relation to new therapeutic approaches for diabetes-obesity. This article is protected by copyright. All rights reserved.

Imaging of neuro-cognitive performance in extreme Environments—A (p)review

Science.gov (United States)

Schneider, Stefan; Bubeev, Juri A.; Choukèr, Alexander; Morukov, Boris; Johannes, Bernd; Strüder, Heiko K.

2012-12-01

Living in extreme environments is accompanied by a number of stressors, which can be classified either as physiological stressors (e.g. microgravity, missing sunlight) or psychological stressors (e.g. confinement). From earth bound studies a negative impact of stress on mental health and cognitive performance is well known and both factors might impair mission success and mission safety during longer inhabitation of space. Accordingly there is the need to identify adequate countermeasures. Nevertheless causal research of neuro-cognitive impairments in space remains speculative due to missing possibilities of brain imaging. Furthermore the reliability of current psychological tests used to assess and monitor cognitive performance in extreme environments seems to be vulnerable due to a lack of compliance. With on-going plans of international space agencies to send people to moon and/or mars, this manuscript aims to summarize and review research attempts of the past two decades and to identify methodological shortcomings. Finally, following the guideline that research has no legacy for its own but must serve the self-concept and well-being of man, this manuscript presents a number of recommendations to enhance future neuro-cognitive research in extreme environments. A deeper insight into neuro-cognitive coherence is not only desirable to understand the effects of stress on mental health, which seems to be a major issue for our current society, and to develop adequate countermeasures but will also help to maintain and improve mission success and mission safety in manned space flight.

dSPACE based adaptive neuro-fuzzy controller of grid interactive inverter

International Nuclear Information System (INIS)

Altin, Necmi; Sefa, İbrahim

2012-01-01

Highlights: ► We propose a dSPACE based neuro-fuzzy controlled grid interactive inverter. ► The membership functions and rule base of fuzzy logic controller by using ANFIS. ► A LCL output filter is designed. ► A high performance controller is designed. - Abstract: In this study, design, simulation and implementation of a dSPACE based grid interactive voltage source inverter are proposed. This inverter has adaptive neuro-fuzzy controller and capable of importing electrical energy, generated from renewable energy sources such as the wind, the solar and the fuel cells to the grid. A line frequency transformer and a LCL filter are used at the output of the grid interactive inverter which is designed as current controlled to decrease the susceptibility to phase errors. Membership functions and rule base of the fuzzy logic controller, which control the inverter output current, are determined by using artificial neural networks. Both simulation and experimental results show that, the grid interactive inverter operates synchronously with the grid. The inverter output current which is imported to the grid is in sinusoidal waveform and the harmonic level of it meets the international standards (4.3 < 5.0%). In addition, simulation and experimental results of the neuro-fuzzy and the PI controlled inverter are given together and compared in detail. Simulation and experimental results show that the proposed inverter has faster response to the reference variations and lower steady state error than PI controller.

Innovative neuro-fuzzy system of smart transport infrastructure for road traffic safety

Science.gov (United States)

Beinarovica, Anna; Gorobetz, Mikhail; Levchenkov, Anatoly

2017-09-01

The proposed study describes applying of neural network and fuzzy logic in transport control for safety improvement by evaluation of accidents’ risk by intelligent infrastructure devices. Risk evaluation is made by following multiple-criteria: danger, changeability and influence of changes for risk increasing. Neuro-fuzzy algorithms are described and proposed for task solution. The novelty of the proposed system is proved by deep analysis of known studies in the field. The structure of neuro-fuzzy system for risk evaluation and mathematical model is described in the paper. The simulation model of the intelligent devices for transport infrastructure is proposed to simulate different situations, assess the risks and propose the possible actions for infrastructure or vehicles to minimize the risk of possible accidents.

Prediction of specific depressive symptom clusters in youth with epilepsy: The NDDI-E-Y versus Neuro-QOL SF.

Science.gov (United States)

Kellermann, Tanja S; Mueller, Martina; Carter, Emma G; Brooks, Byron; Smith, Gigi; Kopp, Olivia J; Wagner, Janelle L

2017-08-01

Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) and the Neuro-QOL Depression Short Form (Neuro-QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Children's Depression Inventory-2 (CDI-2). Cross-sectional study examining 99 YWE (female 68, mean age 14.7 years) during a routine epilepsy visit, who completed self-report measures of depressive symptoms, including the NDDI-E-Y, CDI-2, and the Neuro-QOL SF. Caregivers completed a measure of seizure severity. All sociodemographic and medical information was evaluated through electronic medical record review. After accounting for seizure and demographic variables, the NDDI-E-Y accounted for 45% of the variance in the CDI-2 Total score and the CDI-2 Ineffectiveness subscale. Furthermore, the NDDI-E-Y predicted CDI-2 Total scores and subscales similarly, with the exception of explaining significantly more variance in the CDI-2 Ineffectiveness subscale compared to the Negative Mood subscale. The NDDI-E-Y explained greater variance compared to Neuro-QOL SF across the Total (48% vs. 37%) and all CDI-2 subscale scores; however, the NDDI-E-Y emerged as a stronger predictor of only CDI-2 Ineffectiveness. Both the NDDI-E-Y and Neuro-QOL SF accounted for the lowest amount of variance in CDI-2 Negative Mood. Sensitivity was poor for the Neuro-QOL SF in predicting high versus low CDI-2 scores. The NDDI-E-Y has strong psychometrics and can be easily integrated into routine epilepsy care for quick, brief screening of depressive symptoms in YWE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Recent novel tumor gatekeepers and potential therapeutic approaches

African Journals Online (AJOL)

Keywords: Cancer, Potent inhibitors, Gatekeepers, Therapeutic approaches, Oncogenic pathways. Tropical Journal ..... effects of the target suppression support change from a one gene .... Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017.

Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects

Directory of Open Access Journals (Sweden)

Eva M Marco

2011-10-01

Full Text Available Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders. Cognition and emotionality are the most affected functions in neuropsychiatric disorders, i.e. anxiety disorders, depression and schizophrenia. In this review, most relevant literature on the role of the endocannabinoid (eCB system in neuropsychiatric disorders will be presented. Evidence from clinical and animal studies is provided for the participation of CB1 and CB2 receptors (CB1R and CB2R in the above mentioned neuropsychiatric disorders. CBRs are crucial in some of the emotional and cognitive impairments reported, although more research is required to understand the specific role of the eCB system in neuropsychiatric disorders. Cannabidiol (CBD, the main non-psychotropic component of the Cannabis sativa plant, has shown therapeutic potential in several neuropsychiatric disorders. Although further studies are needed, recent studies indicate that CBD therapeutic effects may partially depend on facilitation of eCB-mediated neurotransmission. Last but not least, this review includes recent findings on the role of the eCB system in eating disorders. A deregulation of the eCB system has been proposed to be in the bases of several neuropsychiatric disorders, including eating disorders. Cannabis consumption has been related to the appearance of psychotic symptoms and schizophrenia. In contrast, the pharmacological manipulation of this eCB system has been proposed as a potential strategy for the treatment of anxiety disorders, depression, and anorexia nervosa. In conclusion, the eCB system plays a critical role in psychiatry; however, detrimental consequences of manipulating this endogenous system cannot be underestimated over the potential and promising perspectives of its therapeutic manipulation.

BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

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Françoise eREDINI

2015-12-01

Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

An investigation into the spiritual needs of neuro-oncology patients from a nurse perspective

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