WorldWideScience

Sample records for blocks central sensitization

  1. Psychosocial Factors and Central Sensitivity Syndromes

    OpenAIRE

    Adams, Leah M.; Turk, Dennis C.

    2015-01-01

    Central sensitivity syndromes (CSSs) represent a heterogeneous group of disorders (e.g., fibromyalgia [FM], irritable bowel syndrome [IBS], chronic headache, temporomandibular disorders [TMDs], pelvic pain syndromes) that share common symptoms, with persistent pain being the most prominent feature.

  2. CENTRAL REINFORCING EFFECTS OF ETHANOL ARE BLOCKED BY CATALASE INHIBITION

    OpenAIRE

    Nizhnikov, Michael Edward; Molina, Juan Carlos; Spear, Norman

    2007-01-01

    Recent studies have systematically indicated that newborn rats are highly sensitive to ethanol’s positive reinforcing effects. Central administrations of ethanol (25–200 mg %) associated with an olfactory conditioned stimulus (CS) promote subsequent conditioned approach to the CS as evaluated through the newborn’s response to a surrogate nipple scented with the CS. It has been shown that ethanol’s first metabolite, acetaldehyde, exerts significant reinforcing effects in the central nervous sy...

  3. Central sensitization in medullary dorsal horn involves gap junctions and hemichannels

    OpenAIRE

    Chiang, Chen Yu; Li, Zhaohui; Dostrovsky, Jonathan O.; Sessle, Barry J.

    2010-01-01

    Central sensitization is a fundamental mechanism contributing to acute and chronic pain conditions. Our previous studies have documented a glutamatergic-, purinergic- and glial-dependent central sensitization that can be induced in rat medullary dorsal horn (MDH) nociceptive neurons by mustard oil (MO) application to the tooth pulp. The present study demonstrated that carbenoxolone, a potent gap junction and hemichannel blocker, completely blocked all parameters of MO-induced central sensitiz...

  4. Central sensitization in humans: assessment and pharmacology.

    Science.gov (United States)

    Arendt-Nielsen, Lars

    2015-01-01

    It is evident that chronic pain can modify the excitability of central nervous system which imposes a specific challenge for the management and for the development of new analgesics. The central manifestations can be difficult to quantify using standard clinical examination procedures, but quantitative sensory testing (QST) may help to quantify the degree and extend of the central reorganization and effect of pharmacological interventions. Furthermore, QST may help in optimizing the development programs for new drugs.Specific translational mechanistic QST tools have been developed to quantify different aspects of central sensitization in pain patients such as threshold ratios, provoked hyperalgesia/allodynia, temporal summation (wind-up like pain), after sensation, spatial summation, reflex receptive fields, descending pain modulation, offset analgesia, and referred pain areas. As most of the drug development programs in the area of pain management have not been very successful, the pharmaceutical industry has started to utilize the complementary knowledge obtained from QST profiling. Linking patients QST profile with drug efficacy profile may provide the fundamentals for developing individualized, targeted pain management programs in the future. Linking QST-assessed pain mechanisms with treatment outcome provides new valuable information in drug development and for optimizing the management regimes for chronic pain.

  5. Archean crustal evolution in the central Minto block, northern Quebec

    International Nuclear Information System (INIS)

    Skulski, T.; Percival, J.A.; Stern, R.A.

    1996-01-01

    The central Minto block contains three volcano-sedimentary successions. Near Lake Qalluviartuuq, an isotopically primitive ( 2.83 Ga ε Nd +3.8 to +2.3) 2.83 Ga volcano-plutonic sequence comprises depleted tholeiitic basalts, anorthositic gabbro, and diorite-granodiorite that is unconformably overlain by 2.76 Ga ε Nd +1.8) calc-alkaline sequence of pillow basalts, andesites, and peridotite cut by 2.73 Ga diorite. To the west, and in inferred tectonic contact, the sediment-dominated Kogaluc sequence includes both isotopically evolved calc-alkaline rocks ( 2.76 Ga ε Nd +1.6 to -0.1) including 2.78Ga ε Nd Nd 2.725Ga ε Nd - 1. 6). (author). 19 refs., 4 tabs., 5 figs

  6. Central reinforcing effects of ethanol are blocked by catalase inhibition.

    Science.gov (United States)

    Nizhnikov, Michael E; Molina, Juan C; Spear, Norman E

    2007-11-01

    Recent studies have systematically indicated that newborn rats are highly sensitive to ethanol's positive reinforcing effects. Central administrations of ethanol (25-200mg %) associated with an olfactory conditioned stimulus (CS) promote subsequent conditioned approach to the CS as evaluated through the newborn's response to a surrogate nipple scented with the CS. It has been shown that ethanol's first metabolite, acetaldehyde, exerts significant reinforcing effects in the central nervous system. A significant amount of acetaldehyde is derived from ethanol metabolism via the catalase system. In newborn rats, catalase levels are particularly high in several brain structures. The present study tested the effect of catalase inhibition on central ethanol reinforcement. In the first experiment, pups experienced lemon odor either paired or unpaired with intracisternal (IC) administrations of 100mg% ethanol. Half of the animals corresponding to each learning condition were pretreated with IC administrations of either physiological saline or a catalase inhibitor (sodium-azide). Catalase inhibition completely suppressed ethanol reinforcement in paired groups without affecting responsiveness to the CS during conditioning or responding by unpaired control groups. A second experiment tested whether these effects were specific to ethanol reinforcement or due instead to general impairment in learning and expression capabilities. Central administration of an endogenous kappa opioid receptor agonist (dynorphin A-13) was used as an alternative source of reinforcement. Inhibition of the catalase system had no effect on the reinforcing properties of dynorphin. The present results support the hypothesis that ethanol metabolism regulated by the catalase system plays a critical role in determination of ethanol reinforcement in newborn rats.

  7. Does central sensitization help explain idiopathic overactive bladder?

    Science.gov (United States)

    Reynolds, W Stuart; Dmochowski, Roger; Wein, Alan; Bruehl, Stephen

    2016-08-01

    The pathophysiological mechanisms underlying overactive bladder syndrome (OAB) can include dysfunction of sensory pathways of the peripheral and central nervous systems, resulting in bladder hypersensitivity. Central sensitization describes an induced state of spinal hypersensitivity that is associated with a variety of chronic pain disorders that share many attributes with OAB, albeit without the presence of pain. As such, the concept of central sensitization might be relevant to understanding the mechanisms and clinical manifestations of OAB syndrome. An understanding of the pathophysiology and clinical manifestations of central sensitization, and the evidence that supports a role of central sensitization in OAB, including the potential implications of mechanisms of central sensitization for the treatment of patients with OAB could provide a novel approach to the treatment of patients with this disease. Such an approach would be especially relevant to those patients with central sensitization-related comorbidities, and has the potential to improve the outcomes of these patients in particular.

  8. Post-treatment lyme syndrome and central sensitization.

    Science.gov (United States)

    Batheja, Shweta; Nields, Jenifer A; Landa, Alla; Fallon, Brian A

    2013-01-01

    Central sensitization is a process that links a variety of chronic pain disorders that are characterized by hypersensitivity to noxious stimuli and pain in response to non-noxious stimuli. Among these disorders, treatments that act centrally may have greater efficacy than treatments acting peripherally. Because many individuals with post-treatment Lyme syndrome (PTLS) have a similar symptom cluster, central sensitization may be a process mediating or exacerbating their sensory processing. This article reviews central sensitization, reports new data on sensory hyperarousal in PTLS, explores the potential role of central sensitization in symptom chronicity, and suggests new directions for neurophysiologic and treatment research.

  9. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.

    Science.gov (United States)

    Ji, Ru-Rong; Nackley, Andrea; Huh, Yul; Terrando, Niccolò; Maixner, William

    2018-02-19

    Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness in central pain pathways after painful insults. Accumulating evidence suggests that central sensitization is also driven by neuroinflammation in the peripheral and central nervous system. A characteristic feature of neuroinflammation is the activation of glial cells, such as microglia and astrocytes, in the spinal cord and brain, leading to the release of proinflammatory cytokines and chemokines. Recent studies suggest that central cytokines and chemokines are powerful neuromodulators and play a sufficient role in inducing hyperalgesia and allodynia after central nervous system administration. Sustained increase of cytokines and chemokines in the central nervous system also promotes chronic widespread pain that affects multiple body sites. Thus, neuroinflammation drives widespread chronic pain via central sensitization. We also discuss sex-dependent glial/immune signaling in chronic pain and new therapeutic approaches that control neuroinflammation for the resolution of chronic pain.

  10. Sensitivity Analysis of Centralized Dynamic Cell Selection

    DEFF Research Database (Denmark)

    Lopez, Victor Fernandez; Alvarez, Beatriz Soret; Pedersen, Klaus I.

    2016-01-01

    and a suboptimal optimization algorithm that nearly achieves the performance of the optimal Hungarian assignment. Moreover, an exhaustive sensitivity analysis with different network and traffic configurations is carried out in order to understand what conditions are more appropriate for the use of the proposed...

  11. Peripheral input and its importance for central sensitization.

    Science.gov (United States)

    Baron, Ralf; Hans, Guy; Dickenson, Anthony H

    2013-11-01

    Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long-term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus-independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non-nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. © 2013 American Neurological Association.

  12. Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

    Science.gov (United States)

    Latremoliere, Alban; Woolf, Clifford J.

    2009-01-01

    Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. Perspective In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. PMID:19712899

  13. Central sensitization: implications for the diagnosis and treatment of pain.

    Science.gov (United States)

    Woolf, Clifford J

    2011-03-01

    Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the

  14. Association between pain, central sensitization and anxiety in postherpetic neuralgia.

    Science.gov (United States)

    Schlereth, T; Heiland, A; Breimhorst, M; Féchir, M; Kern, U; Magerl, W; Birklein, F

    2015-02-01

    In postherpetic neuralgia (PHN), dorsal root ganglia neurons are damaged. According to the proposed models, PHN pain might be associated with nociceptive deafferentation, and peripheral (heat hyperalgesia) or central sensitization (allodynia). In 36 PHN patients, afferent nerve fibre function was characterized using quantitative sensory testing and histamine-induced flare analysis. Psychological factors were evaluated with the Hospital Anxiety and Depression Scale (HADS), disease-related quality of life (QoL) with SF-36 and pain with the McGill questionnaire [pain rating index (PRI)]. The patients were also divided into subgroups according to the presence or absence of brush-evoked allodynia as a sign of central sensitization. For all patients, warm, cold and mechanical detection was impaired (p Central sensitization (i.e., allodynia) might contribute to PHN pain. There was a striking association between anxiety, depression and age, and the magnitude of PHN pain. © 2014 European Pain Federation - EFIC®

  15. Central sensitization in chronic low back pain: A narrative review.

    Science.gov (United States)

    Sanzarello, Ilaria; Merlini, Luciano; Rosa, Michele Attilio; Perrone, Mariada; Frugiuele, Jacopo; Borghi, Raffaele; Faldini, Cesare

    2016-11-21

    Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization.

  16. Central neural alterations predominate in an insect model of nociceptive sensitization.

    Science.gov (United States)

    Tabuena, Dennis R; Solis, Allan; Geraldi, Ken; Moffatt, Christopher A; Fuse, Megumi

    2017-04-01

    Many organisms respond to noxious stimuli with defensive maneuvers. This is noted in the hornworm, Manduca sexta, as a defensive strike response. After tissue damage, organisms typically display sensitized responses to both noxious or normally innocuous stimuli. To further understand this phenomenon, we used novel in situ and in vitro preparations based on paired extracellular nerve recordings and videography to identify central and peripheral nerves responsible for nociception and sensitization of the defensive behavior in M. sexta. In addition, we used the in vivo defensive strike response threshold assayed with von Frey filaments to examine the roles that N-methyl-D-aspartate receptor (NMDAR) and hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels play in this nociceptive sensitization using the inhibitors MK-801 and AP5 (NMDAR), and ivabradine and ZD7288 (HCN). Using our new preparations, we found that afferent activity evoked by noxious pinch in these preparations was conveyed to central ganglia by axons in the anterior- and lateral-dorsal nerve branches, and that sensitization induced by tissue damage was mediated centrally. Furthermore, sensitization was blocked by all inhibitors tested except the inactive isomer L-AP5, and reversed by ivabradine both in vivo and in vitro. Our findings suggest that M. sexta's sensitization occurs through central signal amplification. Due to the relatively natural sensitization method and conserved molecular actions, we suggest that M. sexta may be a valuable model for studying the electrophysiological properties of nociceptive sensitization and potentially related conditions such as allodynia and hyperalgesia in a comparative setting that offers unique experimental advantages. J. Comp. Neurol. 525:1176-1191, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Interpretive geophysical fault map across the central block of Yucca Mountain, Nevada

    International Nuclear Information System (INIS)

    Ponce, D.A.

    1996-01-01

    Geophysical data collected along 29 traverses across the central block of Yucca Mountain in southwest Nevada reveal anomalies associated with known fault sand indicate a number of possible concealed faults beneath the eastern flank of Yucca Mountain. Geophysical interpretations indicate that Midway Valley is characterized by several known and previously unknown faults, that the existence of the Yucca Wash fault is equivocal, and that the central part of the eastern flank of Yucca Mountain is characterized by numerous low-amplitude anomalies that probably reflect numerous small-scale faults. Gravity and magnetic data also reveal several large-amplitude anomalies that reflect larger-scale faulting along the margins of the central block

  18. Electrochemical Characterization of TiO 2 Blocking Layers for Dye-Sensitized Solar Cells

    KAUST Repository

    Kavan, Ladislav

    2014-07-31

    Thin compact layers of TiO2 are grown by thermal oxidation of Ti, by spray pyrolysis, by electrochemical deposition, and by atomic layer deposition. These layers are used in dye-sensitized solar cells to prevent recombination of electrons from the substrate (FTO or Ti) with the hole-conducting medium at this interface. The quality of blocking is evaluated electrochemically by methylviologen, ferro/ferricyanide, and spiro-OMeTAD as the model redox probes. Two types of pinholes in the blocking layers are classified, and their effective area is quantified. Frequency-independent Mott-Schottky plots are fitted from electrochemical impedance spectroscopy. Certain films of the thicknesses of several nanometers allow distinguishing the depletion layer formation both in the TiO2 film and in the FTO substrate underneath the titania film. The excellent blocking function of thermally oxidized Ti, electrodeposited film (60 nm), and atomic-layer-deposited films (>6 nm) is documented by the relative pinhole area of less than 1%. However, the blocking behavior of electrodeposited and atomic-layer-deposited films is strongly reduced upon calcination at 500 °C. The blocking function of spray-pyrolyzed films is less good but also less sensitive to calcination. The thermally oxidized Ti is well blocking and insensitive to calcination. © 2014 American Chemical Society.

  19. Osmophobia in allodynic migraineurs: cause or consequence of central sensitization?

    Science.gov (United States)

    Lovati, C; Giani, L; Castoldi, D; Mariotti D'Alessandro, C; DeAngeli, F; Capiluppi, E; D'Amico, D; Mariani, C

    2015-05-01

    Migraine is a primary headache characterized by recurrent attacks of head pain associated with nausea or vomit, photophobia, phonophobia and osmophobia. The presence of osmophobia during migraine attacks seems to be a very specific complaint. Cutaneous allodynia (CA) is very common in migraineurs, and it is the most evident clinical manifestation of central sensitization, a mechanism involved in migraine chronification. This study was aimed at identifying the possible correlation between osmophobia and CA in migraineurs. 673 migraineurs were studied (492 episodic, 181 chronic). The prevalence of both CA and osmophobia was higher in chronic than in episodic migraineurs. The association between these two symptoms was significant in chronic migraineurs at Chi square test. The highlighted relationship between CA and osmophobia may be interpreted in different ways: central sensitization induced by recurrent pain stimulation may in parallel induce a distortion of both cutaneous sensitivity (CA) and olfaction (osmophobia); alternatively, the recurrent olfactory stimulation in subjects with a hypersensitivity to olfactory stimuli may co-work with repetitive pain stimulation to induce the central sensitization process.

  20. Capsaicin-induced central sensitization evokes segmental increases in trigger point sensitivity in humans.

    Science.gov (United States)

    Srbely, John Z; Dickey, James P; Bent, Leah R; Lee, David; Lowerison, Mark

    2010-07-01

    This study investigated whether inducing central sensitization evokes segmental increases in trigger point pressure sensitivity. We evoked central sensitization at the C(5) segment and validated its presence via mechanical cutaneous sensitivity (brush allodynia) testing. Trigger point pressure sensitivity was quantified using the pain pressure threshold (PPT) value. A 50 cm(2) area of the C(5) dermatome at the right lateral elbow was pretreated with 45 degrees heat for 10 minutes. Test subjects (n = 20) then received topical capsaicin cream (0.075%; Medicis, Toronto, Canada) to the C(5) dermatome, whereas control subjects (n = 20) received a topical placebo cream (Biotherm Massage, Montreal, Canada). PPT readings were recorded from the infraspinatus (C(5,6)) and gluteus medius (L(4,5)S(1)) trigger points at zero (pre-intervention), 10, 20, and 30 minutes after intervention; all PPT readings were normalized to pre-intervention (baseline) values. The difference between the PPT readings at the 2 trigger point sites represents the direct influence of segmental mechanisms on the trigger point sensitivity at the infraspinatus site (PPT(seg)). Test subjects demonstrated statistically significant increases in Total Allodynia scores and significant decreases in PPT(seg) at 10, 20, and 30 minutes after application, when compared with control subjects. These results demonstrate that increases in central sensitization evoke increases in trigger point pressure sensitivity in segmentally related muscles. Myofascial pain is the most common form of musculoskeletal pain. Myofascial trigger points play an important role in the clinical manifestation of myofascial pain syndrome. Elucidating the role of central sensitization in the pathophysiology of trigger points is fundamental to developing optimal strategies in the management of myofascial pain syndrome.

  1. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

    Science.gov (United States)

    Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

    2016-07-01

    Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Sleep features and central sensitization symptoms in primary headache patients.

    Science.gov (United States)

    de Tommaso, Marina; Delussi, Marianna; Vecchio, Eleonora; Sciruicchio, Vittorio; Invitto, Sara; Livrea, Paolo

    2014-09-26

    Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain. One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM). Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration. Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development.

  3. Association and Structure of Thermo Sensitive Comblike Block Copolymers in Aqueous Solutions

    International Nuclear Information System (INIS)

    Cheng, Gang

    2008-01-01

    The structures and association properties of thermo sensitive poly(methoxyoligo(ethylene glycol) norbornenyl esters) block copolymers in D2O were investigated by Small Angle Neutron Scattering (SANS). Each block is a comb-like polymer with a polynorbornene (PNB) backbone and oligo ethylene glycol (OEG) side chains (one side chain per NB monomer). The chemical formula of the block copolymer is (OEG3NB)79-(OEG6.6NB)67, where subscripts represent the degree of polymerization (DP) of OEG and NB in each block The polymer concentration was fixed at 2.0 wt % and the structural changes were investigated over a temperature range between 25 C and 68 C. It was found that at room temperature polymers associate to form micelles with a spherical core formed by the block (OEG3NB)79 and corona formed by the block (OEG6.6NB)67 and that the shape of the polymer in the corona could be described by the form factor of rigid cylinders. At elevated temperatures, the aggregation number increases and the micelles become more compact. At temperatures round the cloud point temperature (CPT) T = 60 C a correlation peak started to appear and became pronounced at 68 C due to the formation of a partially ordered structure with a correlation length ∼ 349

  4. Enhanced Pain Sensitivity Among Individuals With Symptomatic Knee Osteoarthritis: Potential Sex Differences in Central Sensitization.

    Science.gov (United States)

    Bartley, Emily J; King, Christopher D; Sibille, Kimberly T; Cruz-Almeida, Yenisel; Riley, Joseph L; Glover, Toni L; Goodin, Burel R; Sotolongo, Adriana S; Herbert, Matthew S; Bulls, Hailey W; Staud, Roland; Fessler, Barri J; Redden, David T; Bradley, Laurence A; Fillingim, Roger B

    2016-04-01

    Symptomatic knee osteoarthritis (OA) is a condition commonly associated with increased pain, disability, and functional limitations. Given the poor correspondence between radiographic evidence and clinical pain, central sensitization has been implicated as a potential mechanism underlying pain facilitation in knee OA. Sex may be a moderator of centrally mediated changes in knee OA pain; however, few studies have systematically assessed this. Therefore, the aim of this study was to examine differences in peripheral and central sensitization in men and women with symptomatic knee OA, as well as to determine whether these differences vary across age (middle age versus older age). Participants (n = 288) between the ages of 45 and 85 years completed a battery of quantitative sensory pain procedures assessing sensitivity to contact heat, cold pressor, mechanical pressure, and punctate stimuli. Differences in temporal summation (TS) were examined, as well as measures of clinical pain and functional performance. When compared to men, women exhibited greater sensitivity to multiple pain modalities (i.e., lower heat, cold, pressure thresholds/tolerances, greater TS of pain); however, there were no sex differences in clinical pain, with the exception of greater widespread pain observed in women. Although there were select age-related differences in pain sensitivity, sex differences in pain varied minimally across the age cohort. Overall, these findings provide evidence for greater overall sensitivity to experimental pain in women with symptomatic knee OA compared to men, suggesting that enhanced central sensitivity may be an important contributor to pain in this group. © 2016, American College of Rheumatology.

  5. Measurement Properties of the Central Sensitization Inventory: A Systematic Review.

    Science.gov (United States)

    Scerbo, Thomas; Colasurdo, Joseph; Dunn, Sally; Unger, Jacob; Nijs, Jo; Cook, Chad

    2017-08-29

    Central sensitization (CS) is a phenomenon associated with several medical diagnoses, including postcancer pain, low back pain, osteoarthritis, whiplash, and fibromyalgia. CS involves an amplification of neural signaling within the central nervous system that results in pain hypersensitivity. The purpose of this systematic review was to gather published studies of a widely used outcome measure (the Central Sensitization Inventory [CSI]), determine the quality of evidence these publications reported, and examine the measurement properties of the CSI. Four databases were searched for publications from 2011 (when the CSI was developed) to July 2017. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was applied to evaluate methodological quality and risk of bias. In instances when COSMIN did not offer a scoring system for measurement properties, qualitative analyses were performed. Fourteen studies met inclusion criteria. Quality of evidence examined with the COSMIN checklist was determined to be good to excellent for all studies for their respective measurement property reports. Interpretability measures were consistent when publications were analyzed qualitatively, and construct validity was strong when examined alongside other validated measures relating to CS. An assessment of the published measurement studies of the CSI suggest the tool generates reliable and valid data that quantify the severity of several symptoms of CS. © 2017 World Institute of Pain.

  6. PI3K/Akt Pathway is Required for Spinal Central Sensitization in Neuropathic Pain.

    Science.gov (United States)

    Liu, Wei; Lv, Yanling; Ren, Facheng

    2018-04-01

    Phosphatidylinositol-3-kinase (PI3K) has been identified in the expression of central sensitization after noxious inflammatory stimuli. However, its contribution in neuropathic pain remains to be determined. Here we address the role of PI3K signaling in central sensitization in a model of neuropathic pain, and propose a novel potential drug target for neuropathic pain. Chronic constriction injury (CCI) rat model was used in the study as the model for neuropathic pain. Western blotting, whole-cell patch clamp, and von Frey assay were performed to study biochemical, electrical, and behavioral changes in CCI rats, respectively. A steroid metabolite of the fungi (wortmannin) was used to block PI3K signaling and its effects on CCI rats were tested. PI3K/Akt signaling increased in the spinal cord L4-L6 sections in the CCI rats. CCI also facilitated miniature excitatory postsynaptic potential of dorsal horn substantia gelatinosa neurons, increased phosphorylation of glutamate receptor subunit GluA1 and synapsin at the synapse, and induced mechanic allodynia. Wortmannin reversed biochemical, electrical, and behavioral changes in CCI rats. This study is the first to show PI3K/Akt signaling is required for spinal central sensitization in the CCI neuropathic pain model.

  7. Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory.

    Science.gov (United States)

    Neblett, Randy; Hartzell, Meredith M; Mayer, Tom G; Cohen, Howard; Gatchel, Robert J

    2017-02-01

    The aim of this study was to create and validate severity levels for the central sensitization inventory (CSI), a valid and reliable patient-reported outcome instrument designed to identify patients whose presenting symptoms may be related to a central sensitivity syndrome (CSS; eg, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome), with a proposed common etiology of central sensitization (CS). Based on CSI score means and standard deviations from previously published subject samples, the following CSI severity levels were established: subclinical = 0 to 29; mild = 30 to 39; moderate = 40 to 49; severe = 50 to 59; and extreme = 60 to 100. The concurrent validity of the CSI severity levels was then confirmed in a separate chronic pain patient sample (58% with a CSS diagnosis and 42% without) by demonstrating associations between CSI scores and (1) the number of physician-diagnosed CSSs; (2) CSI score distributions in both CSS and non-CSS patient samples; (3) patient-reported history of CSSs; and (4) patient-reported psychosocial measures, which are known to be associated with CSSs. Compared to the non-CSS patient subsample, the score distribution of the CSS patient subsample was skewed toward the higher severity ranges. CSI mean scores moved into higher severity levels as the number of individual CSS diagnoses increased. Patients who scored in the extreme CSI severity level were more likely to report previous diagnoses of fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, tension/migraine headaches, and anxiety or panic attacks (P < 0.01). CSI severity levels were also associated with patient-reported depressive symptoms, perceived disability, sleep disturbance, and pain intensity (P ≤ 0.02). This study provides support for these CSI severity levels as a guideline for healthcare providers and researchers in interpreting CSI scores and evaluating treatment responsiveness. © 2016 World Institute of Pain.

  8. Blocking neurogenic inflammation for the treatment of acute disorders of the central nervous system.

    Science.gov (United States)

    Lewis, Kate Marie; Turner, Renée Jade; Vink, Robert

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.

  9. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kate Marie Lewis

    2013-01-01

    Full Text Available Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.

  10. Central sensitization in photophobic and non-photophobic migraineurs: possible role of retino nuclear way in the central sensitization process.

    Science.gov (United States)

    Lovati, Carlo; Mariotti, C; Giani, L; D'Amico, D; Sinelli, A; De Angeli, F; Capiluppi, E; Bussone, G; Mariani, C

    2013-05-01

    The aim of the present study was to investigate the possible relationships between the presence of headache-related photophobia and migraine-associated allodynia--a hallmark of central sensitization--among patients with different migraine types. A sample of 456 migraineurs was studied. Our results showed that photophobia was present in a high proportion of patients, with similar figures in patients with episodic migraine or CM, and confirmed that the prevalence of allodynia was higher among CM patients than in those with episodic migraine. We found a clear association between migraine-related allodynia and photophobia only in CM patients. Overall, these findings suggest that light stimulation may contribute to central sensitization of pain pathways in migraineurs, possibly contributing to progression into chronic forms. The possible connections underlying this type of sensitization is offered by the recently published data on a non-image-forming visual retino-thalamo-cortical pathway which may allow photic signals to converge on a thalamic region which is selectively activated during migraine headache.

  11. Axillary Block as the Sole Anesthetic for Peripherally Inserted Central Catheter Placement in an Infant with Goldenhar Syndrome

    Directory of Open Access Journals (Sweden)

    Ma. Carmen Bernardo-Ocampo

    2013-01-01

    Full Text Available The use of peripheral nerve block as the sole anesthetic in infants is not very common. Studies have demonstrated that ultrasound guided (USG peripheral nerve block is associated with higher overall success rate when compared with nerve stimulation (Rubin et al., 2009, and Gelfand et al., 2011. Described below is a medically complex infant who had an USG axillary brachial plexus block for peripherally inserted central catheter (PICC placement.

  12. Salient Ecological Sensitive Regions of Central Western Ghats, India

    Science.gov (United States)

    Ramachandra, T. V.; Bharath, Setturu; Subash Chandran, M. D.; Joshi, N. V.

    2018-02-01

    Ecologically sensitive regions (ESRs) are the `ecological units' with the exceptional biotic and abiotic elements. Identification of ESRs considering spatially both ecological and social dimensions of environmental variables helps in ecological and conservation planning as per Biodiversity Act, 2002, Government of India. The current research attempts to integrate ecological and environmental considerations into administration, and prioritizes regions at Panchayat levels (local administrative unit) in Uttara Kannada district, Central Western Ghats, Karnataka state considering attributes (biological, Geo-climatic, Social, etc.) as ESR (1-4) through weightage score metrics. The region has the distinction of having highest forest area (80.48%) in Karnataka State, India and has been undergoing severe anthropogenic pressures impacting biogeochemistry, hydrology, food security, climate and socio-economic systems. Prioritisation of ESRs helps in the implementation of the sustainable developmental framework with the appropriate conservation strategies through the involvement of local stakeholders.

  13. Factors blocking the development of north - central Rzeszów

    Science.gov (United States)

    Rybka, Adam; Mazur, Rafał

    2017-12-01

    Rzeszów is one of the best developing cities in Poland. Once the small HQ of a principality - due to complicated historical conditioning - it has now become a place where an increasing number of people choose to live. The city with its bursting life, streets and squares starts and ends, however, in an area which only a few dozen years ago still catered for one fifth of the current population. The main reason for this phenomenon is the presence of spatial barriers, which significantly limit the development of the central urban area. This article analyzes the elements, which block the development of the north-central part of Rzeszów. An appropriate diagnosis of the problem may in the future allow the right actions in urban planning to be taken in order to cross these barriers. This may lead to the future development of areas with huge urbanization potential. Investments undertaken by city authorities to develop the northern peripheries of Rzeszów may trigger the development of the central district in this direction. This may occur as a result of concrete design interventions. The new part of the central district should have the scale and proportions of urban space that answer to the needs of a dynamically developing capital of the Podkarpacie region.

  14. Thermally sensitive block copolymer particles prepared via aerosol flow reactor method: Morphological characterization and behavior in water

    OpenAIRE

    Nykänen, Antti; Rahikkala, Antti; Hirvonen, Sami-Pekka; Aseyev, Vladimir; Tenhu, Heikki; Mezzenga, Raffaele; Raula, Janne; Kauppinen, Esko; Ruokolainen, Janne

    2012-01-01

    This work describes properties of thermo-sensitive submicron sized particles having the same chemical composition but different morphologies. These particles have been prepared with an aerosol technique using dimethylformamide solutions of linear polystyrene-block-poly(N-isopropylacrylamide-block-polystyrene, PS-b-PNIPAM-b-PS. The particles were characterized by cryo-electron microscopy, microcalorimetry, and light scattering. Block-copolymers self-assembled within the particles forming onion...

  15. Block copolymer directed synthesis of mesoporous TiO 2 for dye-sensitized solar cells

    KAUST Repository

    Nedelcu, Mihaela

    2009-01-01

    The morphology of TiO2 plays an important role in the operation of solid-state dye-sensitized solar cells. By using polyisoprene-block- ethyleneoxide (PI-b-PEO) copolymers as structure directing agents for a sol-gel based synthesis of mesoporous TiO2, we demonstrate a strategy for the detailed control of the semiconductor morphology on the 10 nm length scale. The careful adjustment of polymer molecular weight and titania precursor content is used to systematically vary the material structure and its influence upon solar cell performance is investigated. Furthermore, the use of a partially sp 2 hybridized structure directing polymer enables the crystallization of porous TiO2 networks at high temperatures without pore collapse, improving its performance in solid-state dye-sensitized solar cells. © 2009 The Royal Society of Chemistry.

  16. Immediate allergic hypersensitivity to quinolones associates with neuromuscular blocking agent sensitization.

    Science.gov (United States)

    Rouzaire, Paul; Nosbaum, Audrey; Mullet, Christine; Diot, Nathalie; Dubost, Rolande; Bienvenu, Françoise; Guilloux, Laurence; Piriou, Vincent; Bienvenu, Jacques; Bérard, Frédéric

    2013-01-01

    We identified a case of quinolone allergic hypersensitivity associated with quaternary ammonium (QA) sensitization, the allergic determinant of neuromuscular blocking agents (NMBAs). Concomitant sensitization to several chemically different drugs is rarely reported and raises the question of a nonfortuitous association. We evaluated a potential association between quinolone immediate allergic hypersensitivity and NMBA sensitization. QA-specific IgE detection was prospectively performed in 26 patients who presented an immediate hypersensitivity reaction to quinolones: 17 with a confirmed allergic hypersensitivity and 9 with allergic hypersensitivity not confirmed. We also included a control population of 88 outpatients without a history of quinolone or NMBA hypersensitivity. Patients with positive QA-specific IgE benefited from a NMBA allergologic workup. The prevalence of positive QA-specific IgE was significantly higher in patients with quinolone allergic hypersensitivity (9/17, 53%) compared with patients with allergic hypersensitivity not confirmed (1/9, 11%) than in controls (3/88, 3.4%). In the quinolone allergic population, ofloxacin elicited inhibition of the 4 positive QA-specific IgE sera tested, in a dose-response manner. Among the 9 patients with positive QA-specific IgE, the QA sensitization (positivity of specific IgE) was confirmed by positive skin tests and/or basophil activation tests to at least 1 NMBA in 5 of the 7 tested patients. We report here the first documentation of a high prevalence of QA sensitization in patients with quinolone allergic hypersensitivity. These results suggest a new way for NMBA sensitization. It thus seems appropriate to investigate NMBA sensitization when quinolone allergic hypersensitivity is diagnosed. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Central Sensitization-Based Classification for Temporomandibular Disorders: A Pathogenetic Hypothesis

    OpenAIRE

    Monaco, Annalisa; Cattaneo, Ruggero; Marci, Maria Chiara; Pietropaoli, Davide; Ortu, Eleonora

    2017-01-01

    Dysregulation of Autonomic Nervous System (ANS) and central pain pathways in temporomandibular disorders (TMD) is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS), a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI) is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s) affected in these diseases. Ultralow frequency transcutaneous electri...

  18. Central sensitization phenomena after third molar surgery: A quantitative sensory testing study

    DEFF Research Database (Denmark)

    Jensen, T.S.; Norholt, S.E.; Svensson, P.

    2008-01-01

    Background: Surgical removal of third molars may carry a risk of developing persistent orofacial pain, and central sensitization appears to play an important role in the transition from acute to chronic pain. Aim: The aim of this study was to investigate sensitization (primarily central...... impacted third molar. Results: Central sensitization for at least one week was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (p ... to single pinprick (p sensitization of the trigeminal nociceptive system for at least one week after the surgery. Our results indicate that even a minor orofacial surgical procedure may be sufficient to evoke signs of both central and peripheral sensitization...

  19. Fabrication of Hyperbranched Block-Statistical Copolymer-Based Prodrug with Dual Sensitivities for Controlled Release.

    Science.gov (United States)

    Zheng, Luping; Wang, Yunfei; Zhang, Xianshuo; Ma, Liwei; Wang, Baoyan; Ji, Xiangling; Wei, Hua

    2018-01-17

    Dendrimer with hyperbranched structure and multivalent surface is regarded as one of the most promising candidates close to the ideal drug delivery systems, but the clinical translation and scale-up production of dendrimer has been hampered significantly by the synthetic difficulties. Therefore, there is considerable scope for the development of novel hyperbranched polymer that can not only address the drawbacks of dendrimer but maintain its advantages. The reversible addition-fragmentation chain transfer self-condensing vinyl polymerization (RAFT-SCVP) technique has enabled facile preparation of segmented hyperbranched polymer (SHP) by using chain transfer monomer (CTM)-based double-head agent during the past decade. Meanwhile, the design and development of block-statistical copolymers has been proven in our recent studies to be a simple yet effective way to address the extracellular stability vs intracellular high delivery efficacy dilemma. To integrate the advantages of both hyperbranched and block-statistical structures, we herein reported the fabrication of hyperbranched block-statistical copolymer-based prodrug with pH and reduction dual sensitivities using RAFT-SCVP and post-polymerization click coupling. The external homo oligo(ethylene glycol methyl ether methacrylate) (OEGMA) block provides sufficient extracellularly colloidal stability for the nanocarriers by steric hindrance, and the interior OEGMA units incorporated by the statistical copolymerization promote intracellular drug release by facilitating the permeation of GSH and H + for the cleavage of the reduction-responsive disulfide bond and pH-liable carbonate link as well as weakening the hydrophobic encapsulation of drug molecules. The delivery efficacy of the target hyperbranched block-statistical copolymer-based prodrug was evaluated in terms of in vitro drug release and cytotoxicity studies, which confirms both acidic pH and reduction-triggered drug release for inhibiting proliferation of He

  20. Central Sensitization-Based Classification for Temporomandibular Disorders: A Pathogenetic Hypothesis

    Directory of Open Access Journals (Sweden)

    Annalisa Monaco

    2017-01-01

    Full Text Available Dysregulation of Autonomic Nervous System (ANS and central pain pathways in temporomandibular disorders (TMD is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS, a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s affected in these diseases. Ultralow frequency transcutaneous electrical nerve stimulation (ULFTENS is extensively used in TMD and in dental clinical practice, because of its effects on descending pain modulation pathways. The Diagnostic Criteria for TMD (DC/TMD are the most accurate tool for diagnosis and classification of TMD. However, it includes CSI to investigate central aspects of TMD. Preliminary data on sensory ULFTENS show it is a reliable tool for the study of central and autonomic pathways in TMD. An alternative classification based on the presence of Central Sensitization and on individual response to sensory ULFTENS is proposed. TMD may be classified into 4 groups: (a TMD with Central Sensitization ULFTENS Responders; (b TMD with Central Sensitization ULFTENS Nonresponders; (c TMD without Central Sensitization ULFTENS Responders; (d TMD without Central Sensitization ULFTENS Nonresponders. This pathogenic classification of TMD may help to differentiate therapy and aetiology.

  1. Central Sensitization-Based Classification for Temporomandibular Disorders: A Pathogenetic Hypothesis.

    Science.gov (United States)

    Monaco, Annalisa; Cattaneo, Ruggero; Marci, Maria Chiara; Pietropaoli, Davide; Ortu, Eleonora

    2017-01-01

    Dysregulation of Autonomic Nervous System (ANS) and central pain pathways in temporomandibular disorders (TMD) is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS), a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI) is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s) affected in these diseases. Ultralow frequency transcutaneous electrical nerve stimulation (ULFTENS) is extensively used in TMD and in dental clinical practice, because of its effects on descending pain modulation pathways. The Diagnostic Criteria for TMD (DC/TMD) are the most accurate tool for diagnosis and classification of TMD. However, it includes CSI to investigate central aspects of TMD. Preliminary data on sensory ULFTENS show it is a reliable tool for the study of central and autonomic pathways in TMD. An alternative classification based on the presence of Central Sensitization and on individual response to sensory ULFTENS is proposed. TMD may be classified into 4 groups: (a) TMD with Central Sensitization ULFTENS Responders; (b) TMD with Central Sensitization ULFTENS Nonresponders; (c) TMD without Central Sensitization ULFTENS Responders; (d) TMD without Central Sensitization ULFTENS Nonresponders. This pathogenic classification of TMD may help to differentiate therapy and aetiology.

  2. Improving Performance via Blocking Layers in Dye-Sensitized Solar Cells Based on Nanowire Photoanodes.

    Science.gov (United States)

    Li, Luping; Xu, Cheng; Zhao, Yang; Chen, Shikai; Ziegler, Kirk J

    2015-06-17

    Electron recombination in dye-sensitized solar cells (DSSCs) results in significant electron loss and performance degradation. However, the reduction of electron recombination via blocking layers in nanowire-based DSSCs has rarely been investigated. In this study, HfO2 or TiO2 blocking layers are deposited on nanowire surfaces via atomic layer deposition (ALD) to reduce electron recombination in nanowire-based DSSCs. The control cell consisting of ITO nanowires coated with a porous shell of TiO2 by TiCl4 treatment yields an efficiency of 2.82%. The efficiency increases dramatically to 5.38% upon the insertion of a 1.3 nm TiO2 compact layer between the nanowire surface and porous TiO2 shell. This efficiency enhancement implies that porous sol-gel coatings on nanowires (e.g., via TiCl4 treatment) result in significant electron recombination in nanowire-based DSSCs, while compact coatings formed by ALD are more advantageous because of their ability to act as a blocking layer. By comparing nanowire-based DSSCs with their nanoparticle-based counterparts, we find that the nanowire-based DSSCs suffer more severe electron recombination from ITO due to the much higher surface area exposed to the electrolyte. While the insertion of a high band gap compact layer of HfO2 between the interface of the conductive nanowire and TiO2 shell improves performance, a comparison of the cell performance between TiO2 and HfO2 compact layers indicates that charge collection is suppressed by the difference in energy states. Consequently, the use of high band gap materials at the interface of conductive nanowires and TiO2 is not recommended.

  3. Naltrexone pretreatment blocks microwave-induced changes in central cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Wen, Y.F.; Horita, A.; Guy, A.W. (Univ. of Washington School of Medicine, Seattle (USA))

    1991-01-01

    Repeated exposure of rats to pulsed, circularly polarized microwaves (2,450-MHz, 2-microseconds pulses at 500 pps, power density 1 mW/cm2, at an averaged, whole-body SAR of 0.6 W/kg) induced biphasic changes in the concentration of muscarinic cholinergic receptors in the central nervous system. An increase in receptor concentration occurred in the hippocampus of rats subjected to ten 45-min sessions of microwave exposure, whereas a decrease in concentration was observed in the frontal cortex and hippocampus of rats exposed to ten 20-min sessions. These findings, which confirm earlier work in the authors' laboratory, were extended to include pretreatment of rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before each session of exposure. The drug treatment blocked the microwave-induced changes in cholinergic receptors in the brain. These data further support the authors' hypothesis that endogenous opioids play a role in the effects of microwaves on central cholinergic systems.

  4. Central sensitization phenomena after third molar surgery: A quantitative sensory testing study

    DEFF Research Database (Denmark)

    Juhl, Gitte Irene; Jensen, Troels Staehelin; Nørholt, Svend Erik

    2008-01-01

    BACKGROUND: Surgical removal of third molars may carry a risk of developing persistent orofacial pain, and central sensitization appears to play an important role in the transition from acute to chronic pain. AIM: The aim of this study was to investigate sensitization (primarily central...... impacted third molar. RESULTS: Central sensitization for at least one week was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (p...surgery. Our results indicate that even a minor orofacial surgical procedure may be sufficient to evoke signs of both central and peripheral sensitization, which may play...

  5. Central sensitization phenomena after third molar surgery: A quantitative sensory testing study

    DEFF Research Database (Denmark)

    Jensen, T.S.; Norholt, S.E.; Svensson, P.

    2008-01-01

    Background: Surgical removal of third molars may carry a risk of developing persistent orofacial pain, and central sensitization appears to play an important role in the transition from acute to chronic pain. Aim: The aim of this study was to investigate sensitization (primarily central...... impacted third molar. Results: Central sensitization for at least one week was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (p ... to single pinprick (p surgery. Our results indicate that even a minor orofacial surgical procedure may be sufficient to evoke signs of both central and peripheral sensitization...

  6. Bedrock geologic map of the central block area, Yucca Mountain, Nye County, Nevada

    International Nuclear Information System (INIS)

    Day, W.C.; Potter, C.J.; Sweetkind, D.S.; Dickerson, R.P.; San Juan, C.A.

    1998-01-01

    Bedrock geologic maps form the foundation for investigations that characterize and assess the viability of the potential high-level radioactive waste repository at Yucca Mountain, Nevada. This study was funded by the US Department of Energy Yucca Mountain Project to provide a detailed (1:6,000-scale) bedrock geologic map for the area within and adjacent to the potential repository area at Yucca Mountain, Nye County, Nevada. Prior to this study, the 1:12,000-scale map of Scott and Bon, (1984) was the primary source of bedrock geologic data for the Yucca Mountain Project. However, targeted detailed mapping within the central block at Yucca Mountain revealed structural complexities along some of the intrablock faults that were not evident at 1:12,000 (Scott and Bonk, 1984). As a result, this study was undertaken to define the character and extent of the dominant structural features in the vicinity of the potential repository. In addition to structural considerations, ongoing subsurface excavation and geologic mapping within the exploratory Studies Facility (ESF), development of a three-dimensional-framework geologic model, and borehole investigations required use of a constituent stratigraphic system to facilitate surface to underground comparisons. The map units depicted in this report correspond as closely as possible to the proposed stratigraphic nomenclature by Buesch and others (1996), as described here

  7. Magnetic investigations along selected high-resolution seismic traverses in the central block of Yucca Mountain, Nevada

    International Nuclear Information System (INIS)

    Ponce, D.A.; Sikora, R.F.; Roberts, C.W.; Morin, R.L.; Halvorson, P.F.

    1995-01-01

    Ground magnetic data collected along several traverses across the central block of Yucca Mountain in southwest Nevada are interpreted. These data were collected as part of an effort to evaluate faulting in the vicinity of a potential nuclear waste repository at Yucca Mountain. Magnetic data and models along traverses across the central block of Yucca Mountain reveal anomalies associated with known faults and indicate a number of possible concealed faults beneath the eastern flank of Yucca Mountain. The central part of the eastern flank of Yucca Mountain is characterized by numerous small-amplitude anomalies that probably reflect small-scale faulting. Magnetic modeling of the terrain along the eastern flank of Yucca Mountain indicates that terrain induced magnetic anomalies of about 100 to 150 nT are present along some profiles where steep terrain exists above the magnetometer

  8. Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

    Science.gov (United States)

    Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

    2011-05-01

    Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

  9. Platelets Play a Central Role in Sensitization to Allergen.

    Science.gov (United States)

    Amison, Richard T; Cleary, Simon; Riffo-Vasquez, Yanira; Bajwa, Maidda; Page, Clive P; Pitchford, Simon C

    2018-01-24

    Platelet activation occurs in patients with allergic inflammation, and platelets can be activated directly by allergen via an IgE-dependent process. Platelets activate antigen-presenting cells (APCs) such as CD11c+ dendritic cells (DCs) in vitro. Whilst CD11c+ DCs are requisite for allergen sensitization, the role of platelets in this process is unknown. We investigated whether platelets were necessary for allergen sensitization. Balb/c mice sensitised to ovalbumin (OVA), were exposed to subsequent aerosolized allergen (OVA challenge). We analysed lung CD11c+ cell activation, co-localization with platelets, and some other indices of inflammation. The role of platelets at the time of allergen sensitization was assessed through platelet depletion experiments restricted to the period of sensitization. Platelets co-localized with airway CD11c+ cells, and this association increased after allergen sensitization, and after subsequent allergen exposure. Temporary platelet depletion (>95%) at the time of allergen sensitization led to a suppression of IgE and IL-4 synthesis, and a decrease in the pulmonary recruitment of eosinophils, macrophages, and lymphocytes after subsequent allergen exposure. Furthermore, in mice previously depleted of platelets at the time of sensitization, the recovered platelet population were shown to have reduced expression of FcɛRI. Pulmonary CD11c+ cell recruitment was suppressed in these mice after allergen challenge, suggesting the migration of CD11c+ cells in vivo may be dependent on direct platelet recognition of allergen. Platelets are necessary for efficient host sensitization to allergen. This propagates the subsequent inflammatory response during secondary allergen exposure, and increases platelet association with airway CD11c+ cells.

  10. Development of a sensitive and specific epitope-blocking ELISA for universal detection of antibodies to human enterovirus 71 strains.

    Directory of Open Access Journals (Sweden)

    Fang He

    Full Text Available BACKGROUND: Human Enterovirus 71 (EV71 is a common cause of hand, foot and mouth disease (HFMD in young children. It is often associated with severe neurological diseases and mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no efficient universal antibody test available to detect EV71 infections. METHODOLOGY/PRINCIPAL FINDING: In the present study, an epitope-blocking ELISA was developed to detect specific antibodies to human EV71 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (Mab 1C6 that specifically binds to capsid proteins in whole EV71 viruses without any cross reaction to any EV71 capsid protein expressed alone. The sensitivity and specificity of the epitope-blocking ELISA for EV71 was evaluated and compared to microneutralization using immunized animal sera to multiple virus genotypes of EV71 and coxsackieviruses. Further, 200 serum sample from human individuals who were potentially infected with EV71 viruses were tested in both the blocking ELISA and microneutralization. Results indicated that antibodies to EV71 were readily detected in immunized animals or human sera by the epitope blocking ELISA whereas specimens with antibodies to other enteroviruses yielded negative results. This assay is not only simpler to perform but also shows higher sensitivity and specificity as compared to microneutralization. CONCLUSION: The epitope-blocking ELISA based on a unique Mab 1C6 provided highly sensitive and 100% specific detection of antibodies to human EV71 viruses in human sera.

  11. Central pain sensitization, COMT Val158Met polymorphism, and emotional factors in fibromyalgia.

    Science.gov (United States)

    Desmeules, Jules; Chabert, Jocelyne; Rebsamen, Michela; Rapiti, Elisabetta; Piguet, Valerie; Besson, Marie; Dayer, Pierre; Cedraschi, Christine

    2014-02-01

    Neurobiological evidence points to altered central nervous system processing of nociceptive stimuli in fibromyalgia. Enzymes like catechol-O-methyl-transferase (COMT) are involved in the elimination of catecholamines playing a possible role in central sensitization and pain. We used quantitative sensory testing to evidence central sensitization in fibromyalgia patients and test whether COMTVal158Met polymorphism, associated with a reduction in enzyme activity, plays a role in sensitized patients. Pain evaluation and quantitative sensory testing were performed including the spinal nociceptive flexion reflex, a physiologic correlate for the evaluation of central nociceptive pathways. Quality of life and distress questionnaires were used. A total of 137 fibromyalgia patients were assessed and compared to 99 matched controls. Central sensitization (nociceptive flexion reflex pain was more likely to be associated with COMT Met/Met genotype. Patients showed important emotional distress compared to controls. In sensitized patients, the COMT Met/Met subgroup showed systematically-though not significantly-worse scores for all psychological variables. The association between COMT p.Val158Met polymorphism and central sensitization in fibromyalgia is essential as it refers to the severity of central sensitization and may be a risk factor for treatment outcome. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  12. Central sensitization-related changes of effective and functional connectivity in the rat inflammatory trigeminal pain model.

    Science.gov (United States)

    Spisák, Tamás; Pozsgay, Zsófia; Aranyi, Csaba; Dávid, Szabolcs; Kocsis, Pál; Nyitrai, Gabriella; Gajári, Dávid; Emri, Miklós; Czurkó, András; Kincses, Zsigmond Tamás

    2017-03-06

    Central sensitization is a key mechanism in the pathology of several neuropathic pain disorders. We aimed to investigate the underlying brain connectivity changes in a rat model of chronic pain. Non-noxious whisker stimulation was used to evoke blood-oxygen-level-dependent (BOLD) responses in a block-design functional Magnetic Resonance Imaging (fMRI) experiment on 9.4T. Measurements were repeated two days and one week after injecting complete Freund's adjuvant into the rats' whisker pad. We found that acute pain reduced activation in the barrel cortex, most probably due to a plateau effect. After one week, increased activation of the anterior cingulate cortex was found. Analyses of effective connectivity driven by stimulus-related activation revealed that chronic pain-related central sensitization manifested as a widespread alteration in the activity of the somatosensory network. Changes were mainly mediated by the anterior cingulate cortex and the striatum and affected the somatosensory and motor cortices and the superior colliculus. Functional connectivity analysis of nested BOLD oscillations justified that the anterior cingular-somatosensory interplay is a key element of network changes. Additionally, a decreased cingulo-motor functional connectivity implies that alterations also involve the output tract of the network. Our results extend the knowledge about the role of the cingulate cortex in the chronification of pain and indicate that integration of multiple connectivity analysis could be fruitful in studying the central sensitization in the pain matrix. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Genesis of iron-apatite ores in Posht-e-Badam Block (Central Iran ...

    Indian Academy of Sciences (India)

    A probable source for this large scale ore forming processes is relatively low partial melting of ... REE composition of the parent magma (Taylor .... Location of the iron-apatite deposits in the southern part of the Posht-e-Badam Block (Bafq region) on the satellite image. sandstones. Some iron-apatite ores of this block are.

  14. Comparison of the Effects of Total Nasal Block and Central Facial Block on Acute Postoperative Pain, Edema, and Ecchymosis After Septorhinoplasty.

    Science.gov (United States)

    Sari, Elif; Simsek, Gokce

    2015-12-01

    Pain, ecchymosis, and edema are major postoperative transient complications of septorhinoplasty procedures. They increase the patient's anxiety and decrease satisfaction levels as well as extend recovery time in the early postoperative period. The aim of this study was to compare the effects of total nasal block (TNB) and central facial block (CFB) on postoperative pain, edema, and ecchymosis. A total of 60 consecutive patients enrolled in this study and were divided into three groups as Controls (n = 20), TNB (n = 20), and CFB (n = 20). The two block methods mentioned above were performed at both the beginning and end of the surgery in the TNB and CFB groups. The Control group was not subjected to any block methods. Pain, edema, and ecchymosis score results according to the three scales were recorded postoperatively after 24 h, and on days 2, 5, 7, and 10. Results were analyzed statistically. Of all patients, 28 were male and 32 were female. Ages were between 18 and 52 years (mean = 26.3 years). Pain, edema, and ecchymosis scores were significantly lower in the TNB and CFB groups than in the Control group. Additionally, there was a significant difference between the TNB and CFB groups in terms of pain and edema at postoperative 24 h and on day 2. Ecchymosis scores were lower in the CFB group than in the TNB group at 24 h and on days 2 and 5 after the operation. Both TNB and CFB decreased postoperative pain, edema, and ecchymosis in septorhinoplasty. However, CFB was more effective than TNB in terms of pain, edema, and ecchymosis relief after septorhinoplasty procedures. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  15. Broadscale postseismic deformation and lower crustal relaxation in the central Bayankala Block (central Tibetan Plateau) observed using InSAR data

    Science.gov (United States)

    Zhao, Dezheng; Qu, Chunyan; Shan, Xinjian; Zuo, Ronghu; Liu, Yunhua; Gong, Wenyu; Zhang, Guohong

    2018-04-01

    We have generated a more than 500 km long postseismic deformation rate map and cumulative displacement time series in the central Bayankala Block of the Tibetan Plateau using ENVISAT/ASAR data from 2003 to 2010 by the π-RATE stacking algorithm. This rate map spans a period of ∼7.2 years and reveals that postseismic motion of 2001 Kokoxili earthquake exhibits a striking signal, dominating crustal deformation of the central Bayankala Block with a cross-fault magnitude ∼9-11 mm/yr in line of sight (LOS) (∼93.1°E). The southern and northern parts of the postseismic deformation field exhibit different patterns and variable magnitudes, reflecting asymmetry of the displacement distribution. Postseismic motion affects eastward extrusion of the central Bayankala Block, which reaches ∼15 km north of the Ganzi-Yushu fault. To further investigate viscoelastic relaxation of the lower crust in this area after approximately two years, E-M, E-M-M and E-S models are constructed. The result shows that the best fit viscosity for the lower crust is about 1 × 1019 Pa·s. Comparison between cumulative displacements resolved by these three models shows that viscoelastic relaxation of the lower crust makes the most significant contribution to postseismic stress relaxation after 2001 event.

  16. Pain: current aspects on peripheral and central sensitization

    OpenAIRE

    Rocha, Anita Perpétua Carvalho; Kraychete, Durval Campos; Lemonica, Lino [UNESP; Carvalho, Lídia Raquel de [UNESP; Barros, Guilherme Antonio Moreira de [UNESP; Garcia, João Batista dos Santos; Sakata, Rioko Kimiko

    2007-01-01

    JUSTIFICATIVA E OBJETIVOS: As pesquisas recentes têm focalizado a plasticidade bioquímica e estrutural do sistema nervoso decorrente da lesão tissular. Os mecanismos envolvidos na transição da dor aguda para crônica são complexos e envolvem a interação de sistemas receptores e o fluxo de íons intracelulares, sistemas de segundo mensageiro e novas conexões sinápticas. O objetivo deste artigo foi discutir os novos mecanismos que envolvem a sensibilização periférica e central. CONTEÚDO: A lesão ...

  17. Central α-adrenoceptors contribute to mustard oil-induced central sensitization in the rat medullary dorsal horn.

    Science.gov (United States)

    Wang, H; Xie, Y F; Chiang, C Y; Dostrovsky, J O; Sessle, B J

    2013-04-16

    Our previous studies have demonstrated that application of the inflammatory irritant mustard oil (MO) to the tooth pulp produces trigeminal central sensitization that includes increases in mechanoreceptive field size and responses to noxious stimuli and decrease in activation threshold in brainstem nociceptive neurons of trigeminal subnucleus caudalis (the medullary dorsal horn, MDH). The aim of the present study was to test if central noradrenergic processes are involved in the central sensitization of MDH neurons and if α1-adrenoceptors or α2-adrenoceptors or both are involved. In urethane/α-chloralose-anesthetized rats, the activity of extracellularly recorded and functionally identified single nociceptive neurons in the MDH was studied. Continuous intrathecal (i.t.) superfusion of the adrenergic modulator guanethidine and α-adrenoceptor blocker phentolamine or selective α1-adrenoceptor antagonist prazosin over the medulla strongly attenuated all three MO-induced parameters of central sensitization in the MDH nociceptive neurons, compared to phosphate-buffered saline (as vehicle control). In contrast, i.t. superfusion of the selective α2-adrenoceptor antagonist yohimbine had little effect on the mechanoreceptive field expansion and the decreased mechanical activation threshold, and indeed facilitated responses to noxious stimuli of sensitized nociceptive neurons. Superfusion of each of the four chemicals alone did not affect baseline nociceptive neuronal properties. These findings provide the first documentation of the involvement of central noradrenergic processes in MDH in the development of the central sensitization, and that α1- and α2-adrenoceptors may be differentially involved. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Do intracellular thiol or peroxidase levels block radiation sensitization by nitrous oxide in some E. coli strains

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, D.; Guilfoil, D.S.; Ohm, M.B. (Hahnemann Univ., Philadelphia, PA (USA). Dept. of Radiation Oncology and Nuclear Medicine)

    1991-01-01

    Although nitrous oxide (N{sub 2}O) is often a radiation sensitizer in procaryotic cells, it fails to sensitize some strains of bacteria, some yeast strains, and most eucaryotic cell lines. At present this inconsistency cannot be satisfactorily explained. The experiments here use eight strains of E. coli, some of which are not sensitized by N{sub 2}O, to test the hypotheses that N{sub 2}O's failure to sensitize might be based on high thiol content or on low peroxidase activity. Our data contradict those hypotheses. In addition, further data show that the strains not sensitized by N{sub 2}O contain no unique cellular component or compound which blocks damage from N{sub 2}O. (author).

  19. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: HYDRO (Hydrography Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing coastal hydrography used in the creation of the Environmental Sensitivity Index (ESI) for Central...

  20. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: HABITATS (Habitat Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for benthic habitats in Central California. Vector polygons in this data set represent kelp and eelgrass...

  1. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: REPTILES (Reptile and Amphibian Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for amphibians and reptiles in Central California. Vector polygons in this data set represent sea turtle...

  2. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: REPTILEL (Reptile and Amphibian Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for amphibians and reptiles in Central California. Vector lines in this data set represent general stream...

  3. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: FISH (Fish Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for marine, estuarine, and anadromous fish species in Central California. Vector polygons in this data set...

  4. Central sensitization in spinal cord injured humans assessed by reflex receptive fields

    DEFF Research Database (Denmark)

    Biurrun Manresa, José Alberto; Finnerup, Nanna Susanne Brix; Johannesen, Inger Lauge

    2014-01-01

    OBJECTIVE: To investigate the effects of central sensitization, elicited by intramuscular injection of capsaicin, by comparing the reflex receptive fields (RRF) of spinally-intact volunteers and spinal cord injured volunteers that present presensitized spinal nociceptive mechanisms. METHODS: Fift...

  5. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Buscher, H.C.J.L.; Goor, H. van; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND AND OBJECTIVES: : Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain

  6. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: FISHL (Fish Lines)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for anadromous fish and rare fish species occurrences in Central California. Vector lines in this data set...

  7. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: INVERT (Invertebrate Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for marine, intertidal/subtidal, and terrestrial invertebrate species in Central California. Vector...

  8. Glutamine uptake contributes to central sensitization in the medullary dorsal horn

    OpenAIRE

    Chiang, Chen Yu; Li, Zhaohui; Dostrovsky, Jonathan O.; Hu, James W.; Sessle, Barry J.

    2008-01-01

    Mustard oil application to tooth pulp produces central sensitization in rat medullary dorsal horn (MDH) nociceptive neurons, which has been implicated in persistent pain mechanisms. We found that superfusion onto MDH of methylaminoisobutyric acid, a competitive inhibitor of the neuronal system A transporter for presynaptic uptake of glutamine (a glutamate precursor released from astroglia), significantly depressed development of mustard oil-induced central sensitization in rat MDH nociceptive...

  9. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice.

    NARCIS (Netherlands)

    Nijs, J.; Houdenhove, B. Van; Oostendorp, R.A.B.

    2010-01-01

    Central sensitization plays an important role in the pathophysiology of numerous musculoskeletal pain disorders, yet it remains unclear how manual therapists can recognize this condition. Therefore, mechanism based clinical guidelines for the recognition of central sensitization in patients with

  10. Low back pain: guidelines for the clinical classification of predominant neuropathic, nociceptive, or central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Apeldoorn, Adri; Hallegraeff, Hank; Clark, Jacqui; Smeets, Rob; Malfliet, Annaleen; Girbes, Enrique L; De Kooning, Margot; Ickmans, Kelly

    2015-01-01

    Low back pain (LBP) is a heterogeneous disorder including patients with dominant nociceptive (e.g., myofascial low back pain), neuropathic (e.g., lumbar radiculopathy), and central sensitization pain. In order to select an effective and preferably also efficient treatment in daily clinical practice, LBP patients should be classified clinically as either predominantly nociceptive, neuropathic, or central sensitization pain. To explain how clinicians can differentiate between nociceptive, neuropathic, and central sensitization pain in patients with LBP. Narrative review and expert opinion Universities, university hospitals and private practices Recently, a clinical method for the classification of central sensitization pain versus neuropathic and nociceptive pain was developed. It is based on a body of evidence of original research papers and expert opinion of 18 pain experts from 7 different countries. Here we apply this classification algorithm to the LBP population. The first step implies examining the presence of neuropathic low back pain. Next, the differential diagnosis between predominant nociceptive and central sensitization pain is done using a clinical algorithm. The classification criteria are substantiated by several original research findings including a Delphi survey, a study of a large group of LBP patients, and validation studies of the Central Sensitization Inventory. Nevertheless, these criteria require validation in clinical settings. The pain classification system for LBP should be an addition to available classification systems and diagnostic procedures for LBP, as it is focussed on pain mechanisms solely.

  11. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial.

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Olesen, S.S.; Drewes, A.M.; Poley, J.W.; Goor, H. van; Wilder-Smith, O.H.G.

    2012-01-01

    BACKGROUND: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect

  12. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial

    NARCIS (Netherlands)

    S.A.W. Bouwense (Stefan); S.S. Olesen (Søren); A.M. Drewes (Asbjørn); J.-W. Poley (Jan-Werner); H. van Goor (Harry); O.H.G. Wilder-Smith (Oliver)

    2012-01-01

    textabstractBackground: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate

  13. Spinal and supraspinal contributions to central sensitization in peripheral neuropathy.

    Science.gov (United States)

    Suzuki, Rie; Dickenson, Anthony

    2005-01-01

    We will focus on spinal cord dorsal horn lamina I projection neurones, their supraspinal targets and involvement in pain processing. These spinal cord neurons respond to tonic peripheral inputs by wind-up and other intrinsic mechanisms that cause central hyper-excitability, which in turn can further enhance afferent inputs. We describe here another hierarchy of excitation - as inputs arrive in lamina I, neurones rapidly inform the parabrachial area (PBA) and periaqueductal grey (PAG), areas associated with the affective and autonomic responses to pain. In addition, PBA can connect to areas of the brainstem that send descending projections down to the spinal cord - establishing a loop. The serotonin receptor, 5HT3, in the spinal cord mediates excitatory descending inputs from the brainstem. These descending excitatory inputs are needed for the full coding of polymodal peripheral inputs from spinal neurons and are enhanced after nerve injury. Furthermore, activity in this serotonergic system can determine the actions of gabapentin (GBP) that is widely used in the treatment of neuropathic pain. Thus, a hierarchy of separate, but interacting excitatory systems exist at peripheral, spinal and supraspinal sites that all converge on spinal neurones. The reciprocal relations between pain, fear, anxiety and autonomic responses are likely to be subserved by these spinal-brainstem-spinal pathways we describe here. Understanding these pain pathways is a first step toward elucidating the complex links between pain and emotions. Copyright 2005 S. Karger AG, Basel

  14. Evidence for central sensitization in chronic whiplash: a systematic literature review.

    Science.gov (United States)

    Van Oosterwijck, J; Nijs, J; Meeus, M; Paul, L

    2013-03-01

    It has been suggested that sensitization of the central nervous system plays an important role in the development and maintenance of chronic (pain) complaints experienced by whiplash patients. According to the PRISMA guidelines, a systematic review was performed to screen and evaluate the existing clinical evidence for the presence of central sensitization in chronic whiplash. DATABASES AND DATA TREATMENT: Predefined keywords regarding central sensitization and chronic whiplash were combined in electronic search engines PubMed and Web of Science. Full text clinical reports addressing studies of central sensitization in human adults with chronic complaints due to a whiplash trauma were included and reviewed on methodological quality by two independent reviewers. From the 99 articles that were identified, 24 met the inclusion criteria, and 22 articles achieved sufficient scores on methodological quality and were discussed. These studies evaluated the sensitivity to different types of stimuli (mechanical, thermal, electrical). Findings suggest that although different central mechanisms seem to be involved in sustaining the pain complaints in whiplash patients, hypersensitivity of the central nervous system plays a significant role. Persistent pain complaints, local and widespread hyperalgesia, referred pain and (thoracic) allodynia, decreased spinal reflex thresholds, inefficient diffuse noxious inhibitory controls activation and enhanced temporal summation of pain were established in chronic whiplash patients. Although the majority of the literature provides evidence for the presence of central sensitization in chronic whiplash, underlying mechanisms are still unclear and future studies with good methodological quality are necessary. In addition, international guidelines for the definition, clinical recognition, assessment and treatment of central sensitization are warranted. © 2012 European Federation of International Association for the Study of Pain Chapters.

  15. Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons.

    Science.gov (United States)

    Lam, D K; Sessle, B J; Hu, J W

    2008-10-15

    Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central

  16. Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis

    DEFF Research Database (Denmark)

    Lluch, Enrique; Nijs, Jo; Courtney, Carol A

    2018-01-01

    BACKGROUND: Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice. AIM: The objective of this perspective is to design a set...... of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice. METHODS: A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement...... on clinically relevant descriptors. RESULTS: It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain...

  17. High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

    Science.gov (United States)

    Vo, L; Drummond, P D

    2013-03-01

    In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

  18. Synthesis and Self-Assembly of Block Copolymers Containing Temperature Sensitive and Degradable Chain Segments.

    Science.gov (United States)

    Gong, Hong-Liang; Lei, Lei; Shi, Shu-Xian; Xia, Yu-Zheng; Chen, Xiao-Nong

    2018-05-01

    In this work, polylactide-b-poly(N-isopropylacrylamide) were synthesized by the combination of controlled ring-opening polymerization and reversible addition fragmentation chain transfer polymerization. These block copolymers with molecular weight range from 7,900 to 12,000 g/mol and narrow polydispersity (≤1.19) can self-assemble into micelles (polylactide core, poly(N-isopropylacrylamide) shell) in water at certain temperature range, which have been evidenced by laser particle size analyzer proton nuclear magnetic resonance and transmission electron microscopy. Such micelles exhibit obvious thermo-responsive properties: (1) Poly(N-isopropylacrylamide) blocks collapse on the polylactide core as system temperature increase, leading to reduce of micelle size. (2) Micelles with short poly(N-isopropylacrylamide) blocks tend to aggregate together when temperature increased, which is resulted from the reduction of the system hydrophilicity and the decreased repulsive force between micelles.

  19. Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors

    Directory of Open Access Journals (Sweden)

    Simmonds Peter

    2008-01-01

    Full Text Available Abstract Background HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node. Results R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542, but with increased resistance to the anti-CD4 monoclonal antibody (mab, Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120. Conclusion Variation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.

  20. The role of central sensitization in shoulder pain: A systematic literature review.

    Science.gov (United States)

    Sanchis, Marc N; Lluch, Enrique; Nijs, Jo; Struyf, Filip; Kangasperko, Maija

    2015-06-01

    Hyperexcitability of the central nervous system has been suggested to play an important role in pain experienced by patients with unilateral shoulder pain. A systematic literature review following the PRISMA guidelines was performed to evaluate the existing evidence related to the presence of central sensitization in patients with unilateral shoulder pain of different etiologies including those with chronic subacromial impingement syndrome. Studies addressing neuropathic pain (e.g., post-stroke shoulder pain) were not considered. Electronic databases PubMed, EBSCO, and Web of Science were searched to identify relevant articles using predefined keywords regarding central sensitization and shoulder pain. Articles were included till September 2013. Full-text clinical reports addressing studies of central sensitization in human adults with unilateral shoulder complaints including those diagnosed with subacromial impingement syndrome were included and screened for methodological quality by two independent reviewers. A total of 10 articles were retrieved for quality assessment and data extraction. All studies were cross-sectional (case-control) or longitudinal in nature. Different subjective and objective parameters, considered manifestations of central sensitization, were established in subjects with unilateral shoulder pain of different etiologies, including those receiving a diagnosis of subacromial impingement syndrome. Overall results suggest that, although peripheral mechanisms are involved, hypersensitivity of the central nervous system plays a role in a subgroup within the shoulder pain population. Although the majority of the literature reviewed provides emerging evidence for the presence of central sensitization in unilateral shoulder pain (including those diagnosed with subacromial impingement syndrome), our understanding of the role central sensitization plays in the shoulder pain population is still in its infancy. Future studies with high methodical quality

  1. Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis.

    Science.gov (United States)

    Lluch, Enrique; Nijs, Jo; Courtney, Carol A; Rebbeck, Trudy; Wylde, Vikki; Baert, Isabel; Wideman, Timothy H; Howells, Nick; Skou, Søren T

    2017-08-02

    Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice. The objective of this perspective is to design a set of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice. A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement on clinically relevant descriptors. It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain and its association with structural joint changes, pain distribution, behavior of knee pain, presence of neuropathic-like or centrally mediated symptoms and responsiveness to previous treatment. The latter includes assessment of response to clinical test, mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and reduced vibration sense. This article describes a set of clinically relevant descriptors that might indicate the presence of central sensitization in patients with knee osteoarthritis in clinical practice. Although based on research data, the descriptors proposed in this review require experimental testing in future studies. Implications for Rehabilitation Laboratory evaluation of central sensitization for people with knee osteoarthritis is yet to be incorporated into clinical practice. A set of clinical indicators for the recognition of central sensitization in patients with knee osteoarthritis is proposed. Although based on research data, the clinical indicators proposed require further experimental testing of psychometric properties.

  2. Central sensitization in patients with rheumatoid arthritis: a systematic literature review.

    Science.gov (United States)

    Meeus, Mira; Vervisch, Stijn; De Clerck, Luc S; Moorkens, Greta; Hans, Guy; Nijs, Jo

    2012-02-01

    The goal of the present study is to systematically review the scientific literature addressing central sensitization and central nociceptive processing in patients with rheumatoid arthritis (RA). To identify relevant articles, we searched PubMed and Web of Science. The search strategy was a combination of terms of the following groups: "Rheumatoid arthritis," inflammatory joint pain, or arthritis; AND (central) sensitization, (central) hypersensitivity, central hyperexcitability, pain modulation, pain processing, neural inhibition, or pain physiopathology; AND pain, nociception, hyperalgesia, pain threshold, or algometry. Articles fulfilling the inclusion criteria were screened for methodologic quality with specific checklists to evaluate different study designs (2 independent raters). Twenty-four full-text articles were included, of which the majority were case-control studies, followed by nonsystematic reviews, cross-sectional studies, and case reports. Methodologic quality was very heterogeneous. Preliminary evidence for generalized hyperalgesia in RA is available. In addition, the mechanism behind impaired central nociceptive processing remains rather obscure. The role of cytokines and neuropeptides especially remains to be elucidated. Windup appears to develop more easily in RA, but evidence in support of impaired nociceptive inhibition and cognitive emotional sensitization (sensitization due to cognitive bias) is scarce. The symmetrical manifestation of the disease, the poor relation between disease activity and symptoms, and the generalized hyperalgesia at both articular and nonarticular sites for different kinds of stimuli are indicative of the presence of central sensitization in RA patients. Further research is required to provide firm evidence in support of various aspects of central sensitization in humans with RA. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Torres-Cueco, Rafael; van Wilgen, C Paul; Girbes, Enrique Lluh; Struyf, Filip; Roussel, Nathalie; van Oosterwijck, Jessica; Daenen, Liesbeth; Kuppens, Kevin; Vanwerweeen, Luc; Hermans, Linda; Beckwee, David; Voogt, Lennard; Clark, Jacqui; Moloney, Niamh; Meeus, Mira

    2014-01-01

    The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists. Designing the first set of classification criteria for the classification of central sensitization pain. A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain. It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory). Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies. Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain.

  4. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

    Science.gov (United States)

    Kim, Yu Shin; Chu, Yuxia; Han, Liang; Li, Man; Li, Zhe; LaVinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong

    2014-02-19

    The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Pru p 3, a marker allergen for lipid transfer protein sensitization also in Central Europe.

    Science.gov (United States)

    Mothes-Luksch, N; Raith, M; Stingl, G; Focke-Tejkl, M; Razzazi-Fazeli, E; Zieglmayer, R; Wöhrl, S; Swoboda, I

    2017-09-01

    In the Mediterranean area, lipid transfer proteins (LTPs) are important causes of plant-food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract-based diagnosis is often complicated by co-sensitization to Bet v 1, the major birch pollen allergen, its cross-reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant-derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant-food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients. © 2017 The Authors Allergy Published by John Wiley & Sons Ltd.

  6. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus.

    Science.gov (United States)

    Hark, A T; Schoenherr, C J; Katz, D J; Ingram, R S; Levorse, J M; Tilghman, S M

    2000-05-25

    The Insulin-like growth factor 2 (Igf2) and H19 genes are imprinted, resulting in silencing of the maternal and paternal alleles, respectively. This event is dependent upon an imprinted-control region two kilobases upstream of H19 (refs 1, 2). On the paternal chromosome this element is methylated and required for the silencing of H19 (refs 2-4). On the maternal chromosome the region is unmethylated and required for silencing of the Igf2 gene 90 kilobases upstream. We have proposed that the unmethylated imprinted-control region acts as a chromatin boundary that blocks the interaction of Igf2 with enhancers that lie 3' of H19 (refs 5, 6). This enhancer-blocking activity would then be lost when the region was methylated, thereby allowing expression of Igf2 paternally. Here we show, using transgenic mice and tissue culture, that the unmethylated imprinted-control regions from mouse and human H19 exhibit enhancer-blocking activity. Furthermore, we show that CTCF, a zinc finger protein implicated in vertebrate boundary function, binds to several sites in the unmethylated imprinted-control region that are essential for enhancer blocking. Consistent with our model, CTCF binding is abolished by DNA methylation. This is the first example, to our knowledge, of a regulated chromatin boundary in vertebrates.

  7. Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

    Science.gov (United States)

    Darbari, Deepika S; Vaughan, Kathleen J; Roskom, Katherine; Seamon, Cassie; Diaw, Lena; Quinn, Meghan; Conrey, Anna; Schechter, Alan N; Haythornthwaite, Jennifer A; Waclawiw, Myron A; Wallen, Gwenyth R; Belfer, Inna; Taylor, James G

    2017-10-01

    Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain. We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls. Static thermal testing using cold stimuli showed lower pain thresholds (p=0.04) and tolerance (p=0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (pcentral sensitization in SCA. The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization. Copyright © 2017 Scandinavian Association for the Study of Pain. All rights reserved.

  8. Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.

    Science.gov (United States)

    Walitt, Brian; Ceko, Marta; Gracely, John L; Gracely, Richard H

    2016-01-01

    Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and nonpainful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.

  9. Multifunctional alumina/titania hybrid blocking layer modified nanocrystalline titania films as efficient photoanodes in dye sensitized solar cells

    Science.gov (United States)

    Wang, Changlei; Yu, Zhenhua; Bu, Chenghao; Liu, Pei; Bai, Sihang; Liu, Chang; Kondamareddy, Kiran Kumar; Sun, Weiwei; Zhan, Kan; Zhang, Kun; Guo, Shishang; Zhao, Xingzhong

    2015-05-01

    A facile way of fabricating efficient blocking layer on mesoporous TiO2 film of dye-sensitized solar cells (DSSCs) is demonstrated here for the first time. Al2O3 and TiO2 are combined together to form a blocking layer. A simple spin coating technique is employed which is a versatile and low-cost method over the atomic layer deposition (ALD) technique. Multifunctional alumina/titania (Al2O3/TiO2) hybrid overlayer is prepared on traditional TiO2 nanocrystalline thin film surface, through sequential deposition of AlCl3·6H2O and TiCl4 precursor solutions followed by sintering at 500 °C for 30 min. Al2O3 effectively plays its role in retarding interfacial recombination of electrons and improving open circuit potential (Voc), while the tiny TiO2 clusters synthesized from TiCl4 treatment act as electron transporting channels to facilitate electron diffusion which leads to enhanced photocurrent (Jsc). Compared to the device without blocking layer, the DSSCs assembled with Al2O3/TiO2 hybrid blocking layer showed improvement in Jsc (from 13.09 mA/cm2 to 16.90 mA/cm2) as well as in Voc (from 0.72 V to 0.73 V) resulting a much better conversion efficiency of 8.60%.

  10. Experimental Pain Responses Support Peripheral and Central Sensitization in Patients with Unilateral Shoulder Pain

    Science.gov (United States)

    Coronado, Rogelio A.; Simon, Corey B.; Valencia, Carolina; George, Steven Z.

    2013-01-01

    Objective The aims of this study were to 1) examine the pattern of experimental pain responses in the affected and non-affected extremities in patients with shoulder pain and 2) explore the intra-individual association between sensitization states derived from experimental pain testing. Methods Experimental pain responses from 58 patients with shoulder pain (17 females, ages 18 to 52) were compared to those from 56 age- and sex-matched healthy volunteers (16 females, ages 21 to 58). Experimental pain responses included pressure pain threshold (PPT), thermal pain threshold and tolerance, and suprathreshold heat pain response (SHPR). Comparisons were made between the affected and non-affected extremity of clinical participants and the average response of extremities in healthy participants. Peripheral and central sensitization indexes were computed for clinical participants using standardized scores and percentile cut-offs based on the data from the healthy control sample. Experimental pain responses in clinical participants observed beyond the 25th and 75th percentile of healthy control sample responses were used for investigation of intra-individual association of sensitization states. Results PPT on the affected side acromion and masseter of clinical participants were diminished compared to their non-affected side (p shoulder pain present with variable patterns of peripheral and central sensitization. Conclusions Collectively, experimental pain responses supported peripheral and central sensitization in response to pressure and thermal stimuli. No clear association was made between individuals exhibiting peripheral or central sensitization and suggests heterogeneity in pain processing in this clinical population. PMID:23619203

  11. Central sensitization syndrome and the initial evaluation of a patient with fibromyalgia: a review.

    Science.gov (United States)

    Fleming, Kevin C; Volcheck, Mary M

    2015-04-01

    In both primary care and consultative practices, patients presenting with fibromyalgia (FM) often have other medically unexplained somatic symptoms and are ultimately diagnosed as having central sensitization (CS). Central sensitization encompasses many disorders where the central nervous system amplifies sensory input across many organ systems and results in myriad symptoms. A pragmatic approach to evaluate FM and related symptoms, including a focused review of medical records, interviewing techniques, and observations, is offered here, giving valuable tools for identifying and addressing the most relevant symptoms. At the time of the clinical evaluation, early consideration of CS may improve the efficiency of the visit, reduce excessive testing, and help in discerning between typical and atypical cases so as to avoid an inaccurate diagnosis. Discussion of pain and neurophysiology and sensitization often proves helpful.

  12. Central Sensitization Syndrome and the Initial Evaluation of a Patient with Fibromyalgia: A Review

    Directory of Open Access Journals (Sweden)

    Kevin C. Fleming

    2015-04-01

    Full Text Available In both primary care and consultative practices, patients presenting with fibromyalgia (FM often have other medically unexplained somatic symptoms and are ultimately diagnosed as having central sensitization (CS. Central sensitization encompasses many disorders where the central nervous system amplifies sensory input across many organ systems and results in myriad symptoms. A pragmatic approach to evaluate FM and related symptoms, including a focused review of medical records, interviewing techniques, and observations, is offered here, giving valuable tools for identifying and addressing the most relevant symptoms. At the time of the clinical evaluation, early consideration of CS may improve the efficiency of the visit, reduce excessive testing, and help in discerning between typical and atypical cases so as to avoid an inaccurate diagnosis. Discussion of pain and neurophysiology and sensitization often proves helpful.

  13. Geochronological data on the Amsinassene-Tefedest Block (Central Hoggar, Algerian Sahara) and evidence for its polycyclic evolution

    International Nuclear Information System (INIS)

    Vialette, Y.; Vitel, G.

    1979-01-01

    The history of the Amsinassene-Tefedest Block, in the central Hoggar domain, is characterized by a polycyclic evolution. The unreliable 1970 Ma age obtained on the Arechchoum gneisses, known to be Suggarian-Eburnean, might represent the effect of the Eburnean orogeny. A Rb/Sr whole-rock age on the leucocratic fractions of gneisses point to a kibaran migmatization. This age confirms the existence of a Kibaran orogeny shown in the Aleksod area. The Pharusian-Pan African cycle, in this domain, is characterized by the emplacement of huge granitic bodies during two distinct magnetic phases: one of Late Proterozoic age (670 Ma) or Imezzarian phase, the other of Cambrian age as shown by the 546 and 515 Ma Rb/Sr whole-rock ages obtained on late kinematic granitic plutons, Iskelian phase. The younger mineral ages (470-430 Ma) indicate late vertical uplift of the central Hoggar. (Auth.)

  14. Central sensitization and MAPKs are involved in occlusal interference-induced facial pain in rats.

    Science.gov (United States)

    Cao, Ye; Li, Kai; Fu, Kai-Yuan; Xie, Qiu-Fei; Chiang, Chen-Yu; Sessle, Barry J

    2013-08-01

    We previously developed a rat dental occlusal interference model of facial pain that was produced by bonding a crown onto the right maxillary first molar and was reflected in sustained facial hypersensitivity that was suggestive of the involvement of central sensitization mechanisms. The aim of the present study was to investigate potential central mechanisms involved in the occlusal interference-induced facial hypersensitivity. A combination of behavioral, immunohistochemical, Western blot, and electrophysiological recording procedures was used in 98 male adult Sprague Dawley rats that either received the occlusal interference or were sham-operated or naive rats. Immunohistochemically labeled astrocytes and microglia in trigeminal subnucleus caudalis (Vc) showed morphological changes indicative of astrocyte and microglial activation after the occlusal interference. Prolonged upregulation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) was also documented in Vc after placement of the occlusal interference and was expressed in both neurons and glial cells at time points when rats showed peak mechanical facial hypersensitivity. The intrathecal administration of the p38 MAPK inhibitor SB203580 to the medulla significantly inhibited the occlusal interference-induced hypersensitivity, and the ERK inhibitor PD98059 produced an even stronger effect. Central sensitization of functionally identified Vc nociceptive neurons following placement of the occlusal interference was also documented by extracellular electrophysiological recordings, and intrathecal administration of PD98059 could reverse the neuronal central sensitization. These novel findings suggest that central mechanisms including central sensitization of trigeminal nociceptive neurons and non-neuronal processes involving MAPKs play significant roles in the production of occlusal interference-induced facial pain. Central mechanisms including trigeminal nociceptive

  15. Improvement of the Geometrical Stability of the LHC cryodipoles when Blocking the Central Support Post

    CERN Document Server

    Seyvet, Fabien; Fernandez-Cano, Elena D; Jeanneret, Jean Bernard; Poncet, Alain; Tommasini, Davide

    2005-01-01

    The LHC will be equipped with 1232 horizontally curved 16 meter long super-conducting dipole magnets cooled at 1.9 K, supported within their vacuum vessel by three Glass Fiber Resin Epoxy (GFRE) support posts. The two support posts at the dipole extremities were initially designed free to slide longitudinally with respect to the vacuum vessel and the central support post free to slide transversely. However the magnet shape did not retain the tight geometrical tolerances, of the order of fractions of mm, imposed by machine aperture and magnetic corrector centering requirements. Thereafter a modification to the supporting system, removing the initial transversal degree of freedom of the lower flange of the central support post with respect to the vacuum vessel, was designed and implemented. This paper describes the design of the magnet/cryostat interface with and without blockage of the central support post, analyzes the additional mechanical loads related to the modification and reviews the experimental resul...

  16. Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans

    DEFF Research Database (Denmark)

    Rasmussen, V M; Borgen, A E; Jansen, E C

    2015-01-01

    BACKGROUND: Hyperbaric oxygen (HBO2 ) treatment has in animal experiments demonstrated antinociceptive effects. It was hypothesized that these effects would attenuate secondary hyperalgesia areas (SHAs), an expression of central sensitization, after a first-degree thermal injury in humans. METHOD......, compared with control. These new and original findings in humans corroborate animal experimental data. The thermal injury model may give impetus to future human neurophysiological studies exploring the central effects of hyperbaric oxygen treatment....

  17. [Alpha lipoic acid and its antioxidant against cancer and diseases of central sensitization].

    Science.gov (United States)

    Durand, Marisa; Mach, Núria

    2013-01-01

    The alpha lipoic acid (ALA) may control and limit the production of free radicals, influencing the development of pathologies such cancer or central sensitization diseases. However, the molecular mechanisms are still not elucidated. The objective of the present review is to contrast the antioxidant properties of ALA in the prevention and development of pathologies related to the oxidative stress. In this work, more than 100 articles published during the last 20 years that relate ALA consumption and pathologies related to the oxidative stress have been analysed. The articles have been obtained from different specialized databases (PubMed central, Web of science, Elsevier Journal, Science Direct) and included experiments in animals, cells, and humans. Domains evaluated included ALA, central sensitization diseases, free radicals, and ALA. Results from in vitro and laboratory animals experiments demonstrate that ALA controls the cell apoptosis of different type of cancers through out the increase of reactive oxygen species, and decrease of cell growth. Moreover, results demonstrated that ALA presents an antioxidant capacity and the ability to regenerate other antioxidants, which is essential to treat the central sensitization diseases. The ALA plays a significant role as antioxidant and prooxidant in cancer and central sensitization diseases, although more extensive studies are required to determine the clinical significance in humans. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  18. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    Science.gov (United States)

    Bouwense, Stefan A W; Buscher, Hessel C J L; van Goor, Harry; Wilder-Smith, Oliver H G

    2011-01-01

    Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain control affects supraspinal and spinal sensitization. Seventeen CPP were studied preoperatively and 6 weeks after BTS. Pressure pain thresholds (PPT) were measured in clavicle and pancreatic dermatomes reflecting supraspinal and spinal central sensitization, respectively. Patients with increased PPT after BTS (hypoalgesic) were compared to those without (hyperalgesic) and PPT vs. pain numeric rating scale (NRS) changes compared. After BTS, ten patients showed C5 PPT increases (hypoalgesic; median change 87 kPa), 7 patients had unaltered/lower PPT (hyperalgesic; -135 kPa). Preoperative pain NRS was similar between groups (4 vs. 5, P = 0.2). After BTS hypoalgesic group NRS was lower (1 vs. 6; P = 0.008) and NRS change greater (-2 vs. 0; P = 0.005). Whole group NRS and C5 PPT change correlated significantly and negatively (r = 0.53; P central sensitization after BTS was associated with significantly reduced pain scores in a majority of CPP. A subgroup showed no reductions in supraspinal central sensitization after BTS, coupled to no significant pain NRS reduction. Our results suggest that a subgroup of CPP has altered pain processing that may be independent of ongoing peripheral nociceptive input, resulting in persisting pain despite BTS. If confirmed, these results indicate the importance of sensory testing for indications and management of pain treatments.

  19. Differential effects of experimental central sensitization on the time-course and magnitude of offset analgesia.

    Science.gov (United States)

    Martucci, Katherine T; Yelle, Marc D; Coghill, Robert C

    2012-02-01

    Pain perception is temporally altered during states of chronic pain and acute central sensitization; however, the mechanisms contributing to temporal processing of nociceptive information remain poorly understood. Offset analgesia is a phenomenon that reflects the presence of temporal contrast mechanisms for nociceptive information and can provide an end point to study temporal aspects of pain processing. In order to investigate whether offset analgesia is disrupted during sensitized states, 23 healthy volunteers provided real-time continuous visual analogue scale responses to noxious heat stimuli that evoke offset analgesia. Responses to these stimuli were evaluated during capsaicin-heat sensitization (45°C stimulus, capsaicin cream 0.1%) and heat-only sensitization (40°C stimulus, placebo cream). Capsaicin-heat sensitization produced significantly larger regions of secondary mechanical allodynia compared to heat-only sensitization. Although areas of mechanical allodynia were positively related to individual differences in heat pain sensitivity, this relationship was altered at later time points after capsaicin-heat sensitization. Heat hyperalgesia was observed in the secondary region following both capsaicin-heat and heat-only sensitization. Increased latencies to maximal offset analgesia and prolonged aftersensations were observed only in the primary regions directly treated by capsaicin-heat or heat alone. However, contrary to the hypothesis that offset analgesia would be reduced following capsaicin-heat sensitization, the magnitude of offset analgesia remained remarkably intact after both capsaicin-heat and heat-only sensitization in zones of both primary and secondary mechanical allodynia. These data indicate that offset analgesia is a robust phenomenon and engages mechanisms that interact minimally with those supporting acute central sensitization. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights

  20. Experimental pain responses support peripheral and central sensitization in patients with unilateral shoulder pain.

    Science.gov (United States)

    Coronado, Rogelio A; Simon, Corey B; Valencia, Carolina; George, Steven Z

    2014-02-01

    The aims of this study were to (1) examine the pattern of experimental pain responses in the affected and nonaffected extremities in patients with shoulder pain and (2) explore the intraindividual association between sensitization states derived from experimental pain testing. Experimental pain responses from 58 patients with shoulder pain (17 women, aged 18 to 52 y) were compared with those from 56 age-matched and sex-matched pain-free volunteers (16 women, aged 21 to 58 y). Experimental pain responses included pressure pain threshold (PPT), thermal pain threshold and tolerance, and suprathreshold heat pain response. Comparisons were made between the affected and nonaffected extremities of clinical participants and the average response of extremities in control participants. Peripheral and central sensitization indexes were computed for clinical participants using standardized scores and percentile cutoffs on the basis of the data from the control sample. Experimental pain responses in clinical participants observed beyond the 25th and 75th percentile of control sample responses were used for investigation of intraindividual association of sensitization states. PPT at the acromion and masseter on the affected side of clinical participants were diminished compared with that on their nonaffected side (Psensitivity in clinical participants was noted for PPT at the acromion and suprathreshold heat pain response (Pcentral sensitization indexes demonstrated that individuals with shoulder pain present with variable patterns of peripheral and central sensitization. Collectively, experimental pain responses supported peripheral and central sensitization in response to pressure and thermal stimuli. No clear association was made between individuals exhibiting peripheral or central sensitization, thus suggesting heterogeneity in pain processing in this clinical population.

  1. Differential sensitivity to regional-scale drought in six central US grasslands.

    Science.gov (United States)

    Knapp, Alan K; Carroll, Charles J W; Denton, Elsie M; La Pierre, Kimberly J; Collins, Scott L; Smith, Melinda D

    2015-04-01

    Terrestrial ecosystems often vary dramatically in their responses to drought, but the reasons for this are unclear. With climate change forecasts for more frequent and extensive drought in the future, a more complete understanding of the mechanisms that determine differential ecosystem sensitivity to drought is needed. In 2012, the Central US experienced the fourth largest drought in a century, with a regional-scale 40% reduction in growing season precipitation affecting ecosystems ranging from desert grassland to mesic tallgrass prairie. This provided an opportunity to assess ecosystem sensitivity to a drought of common magnitude in six native grasslands. We tested the prediction that drought sensitivity is inversely related to mean annual precipitation (MAP) by quantifying reductions in aboveground net primary production (ANPP). Long-term ANPP data available for each site (mean length = 16 years) were used as a baseline for calculating reductions in ANPP, and drought sensitivity was estimated as the reduction in ANPP per millimeter reduction in precipitation. Arid grasslands were the most sensitive to drought, but drought responses and sensitivity varied by more than twofold among the six grasslands, despite all sites experiencing 40% reductions in growing season precipitation. Although drought sensitivity generally decreased with increasing MAP as predicted, there was evidence that the identity and traits of the dominant species, as well as plant functional diversity, influenced sensitivity. A more comprehensive understanding of the mechanisms leading to differences in drought sensitivity will require multi-site manipulative experiments designed to assess both biotic and abiotic determinants of ecosystem sensitivity.

  2. How to explain central sensitization to patients with 'unexplained' chronic musculoskeletal pain : Practice guidelines

    NARCIS (Netherlands)

    Nijs, Jo; van Wilgen, C. Paul; Van Oosterwijck, Jessica; van Ittersum, Miriam; Meeus, Mira

    2011-01-01

    Central sensitization provides an evidence-based explanation for many cases of 'unexplained' chronic musculoskeletal pain. Prior to commencing rehabilitation in such cases, it is crucial to change maladaptive illness perceptions, to alter maladaptive pain cognitions and to reconceptualise pain. This

  3. Sol–Gel Titanium Dioxide Blocking Layers for Dye- Sensitized Solar Cells: Electrochemical Characterization

    Czech Academy of Sciences Publication Activity Database

    Kavan, Ladislav; Zukalová, Markéta; Vik, O.; Havlíček, D.

    2014-01-01

    Roč. 15, č. 6 (2014), s. 1056-1061 ISSN 1439-4235 R&D Projects: GA ČR GA13-07724S Institutional support: RVO:61388955 Keywords : TiO2 * electrochemistry * dye-sensitized solar cell Subject RIV: CG - Electrochemistry Impact factor: 3.419, year: 2014

  4. pH-Sensitive Amphiphilic Block-Copolymers for Transport and Controlled Release of Oxygen

    KAUST Repository

    Patil, Yogesh Raghunath

    2017-05-31

    Saturated fluorocarbons, their derivatives and emulsions are capable of dissolving anomalously high amounts of oxygen and other gases. The mechanistic aspects of this remarkable effect remain to be explored experimentally. Here, the synthesis of a library of amphiphilic fluorous block-copolymers incorporating different fluorinated monomers is described, and the capacity of these copolymers for oxygen transport in water is systematically investigated. The structure of the fluorous monomer employed was found to have a profound effect on both the oxygen-carrying capacity and the gas release kinetics of the polymer emulsions. Furthermore, the release of O2 from the polymer dispersions could be triggered by changing the pH of the solution. This is the first example of a polymer-based system for controlled release of a non-polar, non-covalently entrapped respiratory gas.

  5. Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice.

    Science.gov (United States)

    Marinho, Eduardo A V; Oliveira-Lima, Alexandre J; Yokoyama, Thais S; Santos-Baldaia, Renan; Ribeiro, Luciana T C; Baldaia, Marilia A; da Silva, Raphael Wuo; Hollais, Andre Willian; Talhati, Fernanda; Longo, Beatriz Monteiro; Berro, Lais Fernanda; Frussa-Filho, Roberto

    2017-05-01

    CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine. Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine. Mice were treated with saline or cocaine injections in a 15-day intermittent sensitization treatment and subsequently treated with either vehicle, 1 or 10mg/kg rimonabant in the drug-associated environment for 8 consecutive days. Animals were then challenged with saline and cocaine in the open-field apparatus on subsequent days to evaluate the expression of conditioned and sensitized effects to cocaine. c-Fos protein expression was evaluated in the nucleus accumbens (NAcc), ventral tegmental area (VTA), basolateral amygdala (BLA), medial prefrontal cortex (mPFC) and caudate-putamen (CPu) after the last (cocaine) challenge. Previous treatment with 10mg/kg rimonabant blocked the expression of conditioned hyperlocomotion and behavioral sensitization to cocaine, but not acute cocaine-induced hyperlocomotion. These behavioral effects were accompanied by significant changes in c-Fos expression in the brain reward system. Chronic cocaine sensitization blunted a subsequent acute cocaine-induced increase in c-Fos protein in the NAcc, effect that was reversed by previous treatment with rimonabant. Treatment with 10mg/kg rimonabant also attenuated the significant increase in c-Fos expression in the CPu, mPFC and BLA induced by previous chronic sensitization with cocaine. Our findings add to the evidence that drugs targeting CB1 receptors are good candidates for the treatment of cocaine abuse and provide further insights into the mechanisms underlying endocannabinoid signaling within the brain reward system in the context of cocaine abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Geochemical Constraints on the pre-Cenozoic Subduction History of two Margins of the Chortis Block (Northern Central America)

    Science.gov (United States)

    Geldmacher, J.; Martens, U.; Hoernle, K.; Hauff, F.; Bogaard, P.; Kluegel, A.

    2007-12-01

    The igneous forearc basement along the Pacific coast of northern Central America (between southern Mexico and Costa Rica) comprises a highly tectonized accretionary assemblage of igneous and ultramafic rocks. Volcanic and gabbroic rocks with primitive arc geochemical signatures formed between ~100 and ~180 Ma and are interpreted to have originated by arc magmatism resulting from subduction of the Pacific/Farallon plate. Additionally, the forearc contains geochemically enriched ocean island basalt (OIB)-like units that are interpreted as accreted seamounts and islands of a 100 to ~220 Ma old hotspot track, which most likely originated from a long-extinct hotspot located in the Pacific. Based on their combined Pb, Nd, Hf isotopic compositions an affiliation of these isotopically strongly enriched rocks with the Caribbean Large Igneous Province or the Galápagos hotspot appears unlikely. Rocks of similar age and geochemistry are exposed in the Santa Elena Peninsula of Costa Rica, suggesting that the same type of forearc basement is accreted to the continental Chortis block all the way from southern Mexico to Costa Rica. In contrast, gabbroic rocks of the Motagua suture zone in central Guatemala (El Tambor accretionary complex) show depleted MORB signatures and have igneous ages of ~130Ma. These MOR Gabbros were accreted on the current northern margin of the Chortis block during subduction of proto-Caribbean crust. In contrast, geochemistry of gabbros and diorites of the Sierra de Santa Cruz (SSC) indicate medium to high K-series arc affinity and their Ar/Ar ages range from ~75 to 130 Ma. The SSC is interpreted as the western extension of the early Cuban arc that collided with the Maya block in the latest Cretaceous. Arc-derived volcanic clasts were subsequently shed into the Paleocene Sepur Formation of the Maya block. No evidence of accretion of OIB-like material was found in the Motagua suture or the SSC so far. These new data suggest that proto-Caribbean crust

  7. Central sensitization in spinal cord injured humans assessed by reflex receptive fields.

    Science.gov (United States)

    Biurrun Manresa, José Alberto; Finnerup, Nanna Susanne Brix; Johannesen, Inger Lauge; Biering-Sørensen, Fin; Jensen, Troels Staehelin; Arendt-Nielsen, Lars; Andersen, Ole Kæseler

    2014-02-01

    To investigate the effects of central sensitization, elicited by intramuscular injection of capsaicin, by comparing the reflex receptive fields (RRF) of spinally-intact volunteers and spinal cord injured volunteers that present presensitized spinal nociceptive mechanisms. Fifteen volunteers with complete spinal cord injury (SCI) and fourteen non-injured (NI) volunteers participated in the experiment. Repeated electrical stimulation was applied on eight sites on the foot sole to elicit the nociceptive withdrawal reflex (NWR). RRF were assessed before, 1min after and 60min after an intramuscular injection of capsaicin in the foot sole in order to induce central sensitization. Both groups presented RRF expansion and lowered NWR thresholds immediately after capsaicin injection, reflected by the enlargement of RRF sensitivity areas and RRF probability areas. Moreover, the topography of the RRF sensitivity and probability areas were significantly different in SCI volunteers compared to NI volunteers in terms of size and shape. SCI volunteers can develop central sensitization, despite adaptive/maladaptive changes in synaptic plasticity and lack of supraspinal control. Protective plastic mechanisms may still be functional in SCI volunteers. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Migraine and Central Sensitization: Clinical Features, Main Comorbidities and Therapeutic Perspectives.

    Science.gov (United States)

    de Tommaso, Marina; Sciruicchio, Vittorio

    2016-01-01

    Migraine is a very common neurologic disorder, characterized by recurrent attacks of severe headache, autonomic nervous system dysfunction and in some patients by an aura. Migraine is a very common neurologic disorder of neuro-vascular origin, being amongst the 20 most disabling diseases. Migraine attacks are characterized by severe headache, associated to autonomic nervous system dysfunction and in some patients by aura. Pathophysiology and Role of Central Sensitization: Abnormal neuronal excitability may subtend altered processing of sensory stimuli, leading to cortical spreading depression and trigeminal activation. A dysfunction of pain modulation enhances central sensitization phenomena, contributing to acute allodynia and headache persistence. The peculiarity of migraine pain facilitates the use of analgesics, and causes an adjunctive invalidating tendency toward drug over-use. Comorbidity: Chronic migraine patients are frequently affected by diffuse pain, framed in fibromyalgia diagnosis. This comorbidity seems to be supported by common pathophysiological mechanisms. It may aggravate migraine invalidity being worth of consideration for therapeutic management. Migraine Management: Acute and preventive treatments need to be tailored to single cases. Main comorbidity and factors facilitating central sensitization should be taken into account. The management of migraine patients should include a link between headache centers and general practitioner, in order to provide for a better patient information and treatment just at the onset of the disease. Despite its high epidemiologic impact, migraine is frequently underestimated and destined to evolve into chronic form and drugs abuse. A more focused attention to factors facilitating central sensitization and invalidating comorbidities, should reduce the global burden of the disease. migraine, pathophysiology, central sensitization, fibromyalgia comorbidity, acute and preventive therapy, patients - centered approach.

  9. [Pathophysiology of neuropathic pain: molecular mechanisms underlying central sensitization in the dorsal horn in neuropathic pain].

    Science.gov (United States)

    Yamanaka, Hiroki; Noguchi, Koichi

    2012-11-01

    Neuropathic pain syndromes are clinically characterized by spontaneous pain and evoked pain (hyperalgesia and allodynia). The optimal treatment approach for neuropathic pain is still under development because of the complex pathological mechanisms underlying this type of pain. The spinal cord is an important gateway thorough which peripheral pain signals are transmitted to the brain, and sensitization of the spinal neurons is one of the important mechanisms underlying neuropathic pain. Central sensitization represents enhancement of the function of neuronal circuits in nociceptive pathways and is a manifestation of the remarkable plasticity of the somatosensory nervous system after nerve injury. This review highlights the pathological features of central sensitization, which develops because of (1) injury-induced abnormal inputs from primary afferents, (2) increase in the excitability of dorsal horn neurons, and (3) activated glial cell-derived signals.

  10. ZnS/Al2S3 Layer as a Blocking Layer in Quantum Dot Sensitized Solar Cells

    Science.gov (United States)

    Vafapoor, Borzoo; Fathi, Davood; Eskandari, Mehdi

    2018-03-01

    In this research, the effect of treatment of the CdS/CdSe sensitized ZnO photoanode by ZnS, Al2S3, and ZnS/Al2S3 nanoparticles as a barrier layer on the performance of quantum dot sensitized solar cell is investigated. Current density-voltage ( J- V) characteristics show that cell efficiency is enhanced from 3.62% to 4.82% with treatment of a CdS/CdSe/ZnS sensitized ZnO photoanode by Al2S3 nanoparticles. In addition, short- circuit current density ( J sc) is increased from 11.5 mA/cm2 to 14.8 mA/cm2. The results extracted from electrochemical impedance spectroscopy indicate that charge transfer resistance ( R ct) in photoanode/electrolyte interfaces decreases with deposition of Al2S3 nanoparticles on CdS/CdSe/ZnS sensitized ZnO photoanodes, while the chemical capacitance of photoanode ( C μ ) and electron lifetime ( t n) increase. Also, results revealed that cell performance is considerably decreased with the treatment of the AL2S3 blocking layer incorporated between ZnO nanorods and CdS/CdSe QDs.

  11. Experimentally induced central sensitization in the cervical spine evokes postural stiffening strategies in healthy young adults.

    Science.gov (United States)

    Huntley, Andrew H; Srbely, John Z; Zettel, John L

    2015-02-01

    Dysequilibrium of cervicogenic origin can result from pain and injury to cervical paraspinal tissues post-whiplash; however, the specific physiological mechanisms still remain unclear. Central sensitization is a neuradaptive process which has been clinically associated with conditions of chronic pain and hypersensitivity. Strong links have been demonstrated between pain hypersensitivity and postural deficits post-whiplash; however, the precise mechanisms are still poorly understood. The purpose of this study was to explore the mechanisms of cervicogenic disequilibrium by investigating the effect of experimentally induced central sensitization in the cervical spine on postural stability in young healthy adults. Sixteen healthy young adults (7 males (22.6±1.13 years) and 9 females (22±2.69 years)) performed 30-s full-tandem stance trials on an AMTI force plate under normal and centrally sensitized conditions. The primary outcome variables included the standard deviation of the center of pressure (COP) position in medio-lateral (M-L) and antero-posterior (A-P) directions; sway range of the COP in M-L and A-P directions and the mean power frequency (MPF) of the COP and horizontal ground shear forces. Variability and sway range of the COP decreased with experimental induction of central sensitization, accompanied by an increase in MPF of COP displacement in both M-L and A-P directions, suggesting an increase in postural stiffening post-sensitization versus non-sensitized controls. Future studies need to further explore this relationship in clinical (whiplash, chronic pain) populations. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: T_MAMMAL (Terrestrial Mammal Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for rare/sensitive species occurrences of terrestrial mammals in Central California. Vector polygons in...

  13. Central ghrelin increases food foraging/hoarding that is blocked by GHSR antagonism and attenuates hypothalamic paraventricular nucleus neuronal activation

    Science.gov (United States)

    Thomas, Michael A.; Bartness, Timothy J.

    2015-01-01

    The stomach-derived “hunger hormone” ghrelin increases in the circulation in direct response to time since the last meal, increasing preprandially and falling immediately following food consumption. We found previously that peripheral injection of ghrelin potently stimulates food foraging (FF), food hoarding (FH), and food intake (FI) in Siberian hamsters. It remains, however, largely unknown if central ghrelin stimulation is necessary/sufficient to increase these behaviors regardless of peripheral stimulation of the ghrelin receptor [growth hormone secretagogue receptor (GHSR)]. We injected three doses (0.01, 0.1, and 1.0 μg) of ghrelin into the third ventricle (3V) of Siberian hamsters and measured changes in FF, FH, and FI. To test the effects of 3V ghrelin receptor blockade, we used the potent GHSR antagonist JMV2959 to block these behaviors in response to food deprivation or a peripheral ghrelin challenge. Finally, we examined neuronal activation in the arcuate nucleus and paraventricular hypothalamic nucleus in response to peripheral ghrelin administration and 3V GHSR antagonism. Third ventricular ghrelin injection significantly increased FI through 24 h and FH through day 4. Pretreatment with 3V JMV2959 successfully blocked peripheral ghrelin-induced increases in FF, FH, and FI at all time points and food deprivation-induced increases in FF, FH, and FI up to 4 h. c-Fos immunoreactivity was significantly reduced in the paraventricular hypothalamic nucleus, but not in the arcuate nucleus, following pretreatment with intraperitoneal JMV2959 and ghrelin. Collectively, these data suggest that central GHSR activation is both necessary and sufficient to increase appetitive and consummatory behaviors in Siberian hamsters. PMID:26561646

  14. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Carlton, Susan M; Du, Junhui; Tan, Huai Yu; Nesic, Olivera; Hargett, Gregory L; Bopp, Anne C; Yamani, Ammar; Lin, Qing; Willis, William D; Hulsebosch, Claire E

    2009-12-15

    Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP.

  15. Laser-evoked potential habituation and central sensitization symptoms in childhood migraine.

    Science.gov (United States)

    de Tommaso, Marina; Sciruicchio, Vittorio; Ricci, Katia; Montemurno, Anna; Gentile, Francesco; Vecchio, Eleonora; Barbaro, Maria Grazia Foschino; Simeoni, Michele; Goffredo, Marvita; Livrea, Paolo

    2016-04-01

    Few studies have addressed central sensitization symptoms and pain processing in childhood migraine. Our aims were to examine pain sensitivity and responses, including habituation, evoked by CO2 laser stimuli (laser-evoked potentials (LEPs)) in a cohort of children with migraine compared to non-migraine controls and to determine the correlation between LEP features and signs of central sensitization. Thirty-five patients 8-15 years of age with migraines without aura were evaluated during the inter-critical phase and were compared to 17 controls. LEPs were analyzed, and their main features were correlated with clinical symptoms including allodynia and pericranial tenderness. The laser-evoked pain threshold was lower and the N2P2 vertex complex amplitude was higher in children with migraines. Furthermore, habituation of vertex waves of LEPs clearly showed a tendency toward progressive amplitude enhancement in the migraine group. Acute allodynia and inter-critical pericranial tenderness correlated with trigeminal LEP features, particularly with the abnormal habituation pattern. Abnormalities of pain processing and symptoms of central sensitization appear to be characteristics of children with migraine. Reduced habituation and progressive amplification of cortical responses to laser stimuli indicate an overactive nociceptive system at the onset of migraine, and this hyperactivity may subtend allodynia and pericranial tenderness. Future prospective trials may aid in the early identification of clinical phenotypes that display a tendency to develop into the chronic form of migraine, warranting a timely therapeutic approach. © International Headache Society 2015.

  16. General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression.

    Science.gov (United States)

    Boyer, Nelly; Dallel, Radhouane; Artola, Alain; Monconduit, Lénaïc

    2014-07-01

    Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for

  17. Six years without pholcodine; Norwegians are significantly less IgE-sensitized and clinically more tolerant to neuromuscular blocking agents.

    Science.gov (United States)

    de Pater, G H; Florvaag, E; Johansson, S G O; Irgens, Å; Petersen, M N H; Guttormsen, A B

    2017-05-01

    As a strong inducer of IgE antibodies to substituted ammonium ion epitopes (QAI), pholcodine (PHO) is a postulated cause of allergic anaphylaxis to neuromuscular blocking agents (NMBAs). Three years after withdrawal of PHO in Norway, a significant reduction in IgE sensitization and anaphylaxis reporting was seen. Six-year follow-up study on the effects of PHO withdrawal on IgE sensitization and anaphylaxis reporting. From 650 acute consecutive reports (2005-2013) to the Norwegian Network for Anaphylaxis under Anaesthesia (NARA), total number of reports on suspected anaphylactic reactions, number of reactions where NMBAs were administered, number of reactions where serum IgE antibodies (≥0.35 kU A /l) to suxamethonium (SUX) and PHO were present at time of reaction and anaphylaxis severity grades were retrieved. In addition, NMBA sales and prevalence of IgE sensitization to PHO and SUX among 'allergics' were monitored. From baseline period P0 (PHO on the market) through the first (P1) and second (P2), three-year periods after withdrawal, significant falls in total reports (P IgE antibodies to PHO (P = 0.008) and SUX (P = 0.001) at time of reaction were found. Total NMBA sales in P2 were 83% of P0, and SUX and rocuronium (ROC) together made up 86% of sales throughout the study. Five NMBA-related anaphylactic deaths occurred during P0 and P1 and, however, none during P2. Prevalence of IgE sensitization to SUX in 'allergics' fell to 0% at 4 and 5 years after withdrawal. Six years after PHO withdrawal, the Norwegian population has become significantly less IgE-sensitized and clinically more tolerant to NMBAs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Pre-Cenozoic History of the Jalisco Block (Guerrero Terrane of West-Central Mexico) From U- Pb Geochronology

    Science.gov (United States)

    Valencia, V. A.; Righter, K. O.; Gehrels, G.; Ruiz, J.; Ducea, M.; Rosas-Helguera, J.

    2007-05-01

    The Jalisco Block is a fault-bounded crustal fragment, located along the western edge of the Trans-Mexican Volcanic Belt of west-central Mexico, and it forms part of the Triassic-Jurassic Guerrero terrane. Because of its extensive Miocene-Quaternary volcanic cover and Early Cretaceous-Tertiary intrusions, little is known about its Pre-Tertiary history. U-Pb (LA-MC-ICPMS) zircon geochronology of metasedimentary (Quartz Feldespathic Schist), marine sedimentary and plutonic rocks from several localities of the Jalisco Block (southern Mexico) were determined to constrain the geological evolution of this region. Results for the metasedimentary rocks, which are present as roof pendants, indicate a depositional age between the Late Triassic and Middle Jurassic. The older depositional sequence (Late Triassic) shows an important continental influence with subordinate clusters from the Carboniferous (297 Ma), Ordovician (446 Ma), Late and Middle Proterozoic (760, 1041, 1200, 1500 Ma) and Archean (~~2700 Ma), whereas the youngest depositional sequence (Middle Jurassic) have mainly Jurassic zircons, indicating sedimentation in a restricted basin. Ages of turbiditic marine sediments reveal a maximum depositional age of ~~130 Ma (Early Cretaceous), comparable to zircon populations from other areas of the Guerrero Terrane, and with minor age peaks at 320, 480-560, 743, 997-1260, and ~~2750 Ma. Magmatic granitic rocks from Atenguillo, Puerto Vallarta, Mascota and Tomatlan have ages of ~~60 Ma, ~~74 Ma and 80-90 Ma. These ages overlap with previously determined ages of granites and rhyolitic ash flow tuffs from the Jalisco Block, Baja California, Sonora and Sinaloa states. On the other hand, a granitic sample of Cuale region yielded a middle Jurassic age. Metasedimentary and sedimentary rocks of the Jalisco Block have a depositional evolution similar to coeval formations in the Guerrero and Alisitos terranes. We conclude that this

  19. Thermally sensitive block copolymer particles prepared via aerosol flow reactor method: Morphological characterization and behavior in water.

    Science.gov (United States)

    Nykänen, Antti; Rahikkala, Antti; Hirvonen, Sami-Pekka; Aseyev, Vladimir; Tenhu, Heikki; Mezzenga, Raffaele; Raula, Janne; Kauppinen, Esko; Ruokolainen, Janne

    2012-10-23

    This work describes properties of thermo-sensitive submicron sized particles having the same chemical composition but different morphologies. These particles have been prepared with an aerosol technique using dimethylformamide solutions of linear polystyrene-block-poly(N-isopropylacrylamide-block-polystyrene, PS-b-PNIPAM-b-PS. The particles were characterized by cryo-electron microscopy, microcalorimetry, and light scattering. Block-copolymers self-assembled within the particles forming onion-like, gyroid-like, and spherical morphologies having poly(N-isopropylacrylamide) matrix and physically cross-linking polystyrene domains. The particles were dispersed in aqueous media and their behavior in water was studied both below and above the lower critical solution temperature of poly(N-isopropylacrylamide). We found out that the particles with spherical and gyroid-like morphologies swell considerably in water at 20 °C, whereas at 40 °C the particles resemble more of those studied without water treatment. Light scattering experiments showed that the particles gradually aggregate and precipitate with time at 40 °C. Microcalorimetric studies revealed for all three studied morphologies that PNIPAM undergoes a two-step transition due to the different hydration levels of PNIPAM inside and outside the particles. Thicknesses of the PS and PNIPAM layers within the onion-like particles were analyzed using the TEM micrographs by fitting a model of electron density to the integrated electron intensity data. The surface layer of the particles was found out to be PNIPAM, which was supported by light scattering and microcalorimetry. It was also found out from the TEM micrograph analysis that the width of the outmost PS layer is considerably thinner than the one in the dry state prior to immersion in water, and a degradation scheme is proposed to explain these results.

  20. Large Stokes shift downshifting Eu(III) films as efficiency enhancing UV blocking layers for dye sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, M.; Ahmed, H.; Doran, J.; Norton, B. [Dublin Energy Laboratory, Dublin Institute of Technology (Ireland); Bosch-Jimenez, P.; Della Pirriera, M.; Torralba-Calleja, E.; Gutierrez Tauste, D.; Aubouy, L. [Leitat Technological Center, Terrassa (Spain); Daren, S.; Solomon-Tsvetkov, F. [Daren Laboratories, Ness-Ziona (Israel); Galindo, S.; Voz, C.; Puigdollers, J. [Universitat Politecnica Catalunya, Barcelona (Spain)

    2015-01-01

    Large Stokes shift downshifting organolanthanide complex, Eu(tta){sub 3}phen, is examined for inclusion in polymeric layers to replace the UV blocking layer in dye sensitized solar cell (DSSC) technology. The UV blocking layer increases stability but power conversion efficiency decreases as incident UV photons are not converted into photocurrent. Eu(tta){sub 3}phen doped polymeric film are prepared and attached to DSSC devices following optimized thickness and concentration from a ray-trace numerical model for the specific DSSC. External quantum efficiency is significantly increased in the UV spectral region compared to DSSCs utilizing a passive, non-luminescent, UV-BL. High Eu(tta){sub 3}phen film transparency in the visible range minimizes DSSC EQE losses at visible wavelengths. Short-circuit current (I{sub sc}) enhancement due to downshifting is demonstrated (∝1%) in small-scale DSSC prototypes, where the specific geometry limits the photon collection efficiency and overall enhancement. Model predictions indicate that 2%-3% Isc enhancement is realizable in flexible single DSSC compared to, non-luminescent, UV-BL. Added to this, in outdoor conditions taking into account diffuse light, the increment in I{sub sc} can increase 50% more. Although photostability of the blended LSS-DS polymer films is not sufficient to be useful for medium-long term outdoor PV applications, the results demonstrate that significant efficiency enhancement can be realized. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Atomic layer deposition of high performance ultrathin TiO₂ blocking layers for dye-sensitized solar cells.

    Science.gov (United States)

    Kim, Do Han; Woodroof, Mariah; Lee, Kyoungmi; Parsons, Gregory N

    2013-06-01

    Dye-sensitized solar cells (DSSCs) often use a thin insulating or semiconducting layer (typically TiO₂) between the transparent conductive oxide and the mesoporous TiO₂ to block electron/hole recombination at the conducting oxide/electrolyte interface. The blocking layer (BL) is essential to maintain efficient charge generation under low light conditions, at which DSSCs perform well compared to common semiconductor-based photovoltaic devices. In this work, we show that atomic layer deposition (ALD) can produce ultrathin (ALD BLs are the thinnest optimized DSSC BLs reported to date. The BL retards the open-circuit voltage decay and extends the electron lifetime from ≈0.2 s to more than 10 s at 0.3 V, confirming that the ALD films significantly impede photogenerated charge recombination. By preparing BLs through other deposition techniques, we directly demonstrate that ALD results in better performance, even with thinner films, which is ascribed to the lower pinhole density of ALD materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Architecturally sensitive retrofitting of PV to a residential block in Greece to reduce its carbon footprint

    Science.gov (United States)

    Panopoulou, Ismini

    Photovoltaic power is a unique energy source, with wide distribution potential, which can be integrated within the fabric of individual buildings, transforming the power generation in a less large-scale and regionally located issue. As a result, photovoltaic power is a free, clean and silent electrical supply that can be introduced into cities and residential areas. Over the past years, grid-connected, distributed photovoltaic power systems have become an explosively growing sector worldwide. This trend is expected to be continued in the future and solar systems may become a common building element of building construction. In Greece, where the main focus of the project is concentrated, the extended sunshine and the incentives of the new Renewable Energy Sources law of 2006, give a different perspective in photovoltaic investments. In the case study of Vera Water Residence complex in Athens, the viability of an architecturally sensitive retrofitting of PV was examined, from both financial and environmental aspects. The project was concentrated in one of the complex's buildings which was modelled in TAS simulator in order for the annual heating and cooling loads to be estimated. A closer to the reality estimation of electricity demand was made through the annual electricity bills of the building. The proposed building integrated photovoltaic system was designed in terms of following and respecting the aesthetics of the existing architecture of the complex while being as efficient as possible. The annual energy output and C02 emissions reductions were then calculated through RETScreen software analysis according to the location of the project and the characteristics of the PV system. Finally, an economic analysis has been included to the study, considering the installation cost, the annual savings and the embodied energy of the system, in order for the payback period of the investment to be determined. Finally, a small sensitivity analysis concerning the effect of

  3. [Selectivity and sensitivity to blocking by hydrogen ions of batrachotoxin-modified sodium channels in nerve fiber membranes].

    Science.gov (United States)

    Mozhaeva, G N; Naumov, A P; Khodorov, B I

    1983-01-01

    Currents through normal and batrachotoxin-modified sodium channels in frog nerve were measured under voltage clamp conditions. Measured reversal potentials and the Goldman equation were used to calculate relative permeabilities. The permeability ratios were: PNa: PNH4: PK = 1: 0.47: 0.19. Hydrogen-to-sodium permeability ratio was estimated from reversal potential measurements in Na-free acid (pH 3.7-3.8) solutions. It was 528 +/- 46 for batrachotoxin-modified sodium channels. Modified channels were less sensitive to hydrogen block as compared with normal ones. The difference in apparent pKa for acid group between normal and modified channels was about 0.40.

  4. Processing Effects on Block-Copolymer Based Pressure-Sensitive Adhesives

    Science.gov (United States)

    O'Connor, A. E.; Macosko, C. W.

    2000-03-01

    The goal of this work is to investigate how the variables in the hot-melt coating process affect the microstructure and properties of pressure-sensitive adhesives based on a styrene isoprene styrene triblock copolymer. This polymer is a thermoplastic elastomer, able to be coated at high temperatures and physically crosslinked at lower temperatures. Adhesive tape samples have been made through hot-melt and solvent coating methods. Hot-melt coatings are prepared at speeds up to 110 feet/minute. Materials with the same thermal history have been coated using both methods and then tested for comparison of properties. PSA properties are strongly dependent on the time scale of application and debonding, as revealed by shear rheology data, and three types of performance tests (tack, peel, and shear holding power) are used to capture the various responses. Solvent-coated tape has superior shear strength, while hot-melt-coated tape performs better in peel tests. It is expected that the varying flow and deformation histories of the samples will lead to distinct chain orientations, while the rate of cooling of hot-melt-coated samples may influence the degree of phase separation achieved. These factors will cause the adhesive coatings to have different microstructures and therefore different properties.

  5. The Dutch Central Sensitization Inventory (CSI): Factor Analysis, Discriminative Power, and Test-Retest Reliability.

    Science.gov (United States)

    Kregel, Jeroen; Vuijk, Pieter J; Descheemaeker, Filip; Keizer, Doeke; van der Noord, Robert; Nijs, Jo; Cagnie, Barbara; Meeus, Mira; van Wilgen, Paul

    2016-07-01

    A standardized assessment of central sensitization can be performed with the Central Sensitization Inventory (CSI), an English questionnaire consisting of 25 items relating to current health symptoms. The aim of this study was to translate the CSI into Dutch, to perform a factor analysis to reveal the underlying structure, examine its discriminative power, and test-retest reliability. The CSI was first translated into Dutch. A factor analysis was conducted on CSI data of a large group of chronic pain patients (n=368). The ability to discriminate between chronic pain patients (n=188) and pain-free controls (n=49) was determined and the test-retest reliability for chronic pain patients (n=36) and controls (n=45) with a time interval of 3 weeks was evaluated. The exploratory factor analysis resulted in a 4-factor model based on 20 items, representing the domains "General disability and physical symptoms" (Cronbach α=0.80), "Higher central sensitivity"(Cronbach α=0.78), "Urological and dermatological symptoms"(Cronbach α=0.60), and "Emotional distress"(Cronbach α=0.80). Furthermore, a parsimonious second-order factor model was found, where the factor "General central sensitization" was underlying the 4 first-order factors. Chronic pain patients scored significantly worse on all 4 factors. The test-retest reliability was excellent values in both chronic pain patients (ICC=0.88) and controls (ICC=0.91). The original CSI was translated into Dutch and did not reveal any problems during data acquisition. The domains represented by the 4 factors may be useful in setting up specific patient profiles and treatment targets. To conclude, the Dutch CSI revealed 4 distinguishable domains, showed good internal consistency for the total score and 3 out of 4 domains, good discriminative power, and excellent test-retest reliability.

  6. Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI.

    Science.gov (United States)

    Cagnie, Barbara; Coppieters, Iris; Denecker, Sien; Six, Jasmien; Danneels, Lieven; Meeus, Mira

    2014-08-01

    The aim of the present study was to systematically review the literature addressing pain-induced changes in the brain related to central sensitization in patients with fibromyalgia (FM) using specific functional (rs-fMRI and fMRI) and structural (voxel-based morphometry-VBM) brain MRI techniques. PubMed and Web of Science were searched for relevant literature using different key word combinations related to FM, brain MRI, and central sensitization. Full-text reports fulfilling the inclusion criteria were assessed on risk of bias and reviewed by two independent reviewers. From the 61 articles that were identified, 22 met the inclusion criteria and achieved sufficient methodological quality. Overall, eight articles examined structural brain (VBM) changes in patients with FM, showing moderate evidence that central sensitization is correlated with gray matter volume decrease in specific brain regions (mainly anterior cingulate cortex and prefrontal cortex). However, global gray matter volume remains unchanged. A total of 13 articles evaluated brain activity (fMRI) in response to a nociceptive stimulus. Findings suggest a higher but similar pattern of activation of the pain matrix in FM patients compared to controls. There is also evidence of decreased functional connectivity in the descending pain-modulating system in FM patients. Overall, two articles examined intrinsic brain connectivity in FM patients with rs-fMRI. In conclusion, there is moderate evidence for a significant imbalance of the connectivity within the pain network during rest in patients with FM. The included studies showed a moderate evidence for region-specific changes in gray matter volume, a decreased functional connectivity in the descending pain-modulating system, and an increased activity in the pain matrix related to central sensitization. More research is needed to evaluate the cause-effect relationship. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization.

    Science.gov (United States)

    Vera-Portocarrero, L P; Zhang, E-T; Ossipov, M H; Xie, J Y; King, T; Lai, J; Porreca, F

    2006-07-21

    Nerve injury can produce hypersensitivity to noxious and normally innocuous stimulation. Injury-induced central (i.e. spinal) sensitization is thought to arise from enhanced afferent input to the spinal cord and to be critical for expression of behavioral hypersensitivity. Descending facilitatory influences from the rostral ventromedial medulla have been suggested to also be critical for the maintenance, though not the initiation, of experimental neuropathic pain. The possibility that descending facilitation from the rostral ventromedial medulla is required for the maintenance of central sensitization was examined by determining whether ablation of mu-opioid receptor-expressing cells within the rostral ventromedial medulla prevented the enhanced expression of repetitive touch-evoked FOS within the spinal cord of animals with spinal nerve ligation injury as well as nerve injury-induced behavioral hypersensitivity. Rats received a single microinjection of vehicle, saporin, dermorphin or dermorphin-saporin into the rostral ventromedial medulla and 28 days later, underwent either sham or spinal nerve ligation procedures. Animals receiving rostral ventromedial medulla pretreatment with vehicle, dermorphin or saporin that were subjected to spinal nerve ligation demonstrated both thermal and tactile hypersensitivity, and showed significantly increased expression of touch-evoked FOS in the dorsal horn ipsilateral to nerve injury compared with sham-operated controls at days 3, 5 or 10 post-spinal nerve ligation. In contrast, nerve-injured animals pretreated with dermorphin-saporin showed enhanced behaviors and touch-evoked FOS expression in the spinal dorsal horn at day 3, but not days 5 and 10, post-spinal nerve ligation when compared with sham-operated controls. These results indicate the presence of nerve injury-induced behavioral hypersensitivity associated with nerve injury-induced central sensitization. Further, the results demonstrate the novel concept that once

  8. Cross-cultural adaptation and validity of the Spanish central sensitization inventory.

    Science.gov (United States)

    Cuesta-Vargas, Antonio Ignacio; Roldan-Jimenez, Cristina; Neblett, Randy; Gatchel, Robert J

    2016-01-01

    The Central Sensitization Inventory (CSI) is a new patient-reported instrument, which measures symptoms related to Central Sensitivity Syndromes and Central Sensitization. The aim of this study was to translate the CSI into Spanish, and then to perform a psychometric validation, including a factor analysis to reveal the underlying structure. In this two-stage psychometric study participated 395 subjects with various chronic pain conditions and that were recruited from two Primary Care Centres. The CSI was cross-culturally adapted to Spanish through double forward and backward translations. The psychometric properties were then evaluated with analyses of construct validity, factor structure and internal consistency. One subgroup (n = 45) determined test-retest reliability at 7 days. The Spanish Version of CSI demonstrated high internal consistency (α = 0.872) and test-retest reliability (r = 0.91). Factor structure was one-dimensional and supported construct validity. The psychometric properties of the Spanish version were found to be strong, with high test-retest reliability and internal consistency, with similar psychometric properties to the English language version. Unlike the English version, however, a one factor solution was found to be a best fit for the Spanish version.

  9. Evidence for acute central sensitization to prolonged experimental pain in posttraumatic stress disorder.

    Science.gov (United States)

    Moeller-Bertram, Tobias; Strigo, Irina A; Simmons, Alan N; Schilling, Jan M; Patel, Piyush; Baker, Dewleen G

    2014-05-01

    Post-traumatic stress disorder (PTSD) and pain have a well-documented high comorbidity; however, the underlying mechanisms of this comorbidity are currently poorly understood. The aim of this psychophysical study was to investigate the behavioral response to a prolonged suprathreshold pain stimulus in subjects with combat-related PTSD and combat controls (CC) for clinical evidence of central sensitization. Ten male subjects with current PTSD related to combat and 11 CC male subjects underwent baseline quantitative sensory testing (QST), temporal pain summation, and psychological profiling followed by an intramuscular injection of capsaicin into the quadriceps muscle. There was no significant between-group difference for the initial maximal pain response or an initial pain reduction for the first 15 minutes postinjection on QST or pain ratings. However, we observed significantly higher scores in the PTSD group for the second 15 minutes postinjection on both pain intensity and pain unpleasantness ratings. Assessment of temporal summation to repetitive pressure stimuli showed significantly higher subjective pain in the PTSD group. These findings are consistent with a significantly higher degree of acute central sensitization in individuals with PTSD. Increased acute central sensitization may underlie increased vulnerability for developing pain-related conditions following combat trauma. Wiley Periodicals, Inc.

  10. Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: evidence of central processing in unilateral neuropathy.

    Science.gov (United States)

    Fernández-de-las-Peñas, César; de la Llave-Rincón, Ana Isabel; Fernández-Carnero, Josué; Cuadrado, María Luz; Arendt-Nielsen, Lars; Pareja, Juan A

    2009-06-01

    The aim of this study was to investigate whether bilateral widespread pressure hypersensitivity exists in patients with unilateral carpal tunnel syndrome. A total of 20 females with carpal tunnel syndrome (aged 22-60 years), and 20 healthy matched females (aged 21-60 years old) were recruited. Pressure pain thresholds were assessed bilaterally over median, ulnar, and radial nerve trunks, the C5-C6 zygapophyseal joint, the carpal tunnel and the tibialis anterior muscle in a blinded design. The results showed that pressure pain threshold levels were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, the C5-C6 zygapophyseal joint, and the tibialis anterior muscle in patients with unilateral carpal tunnel syndrome as compared to healthy controls (all, P < 0.001). Pressure pain threshold was negatively correlated to both hand pain intensity and duration of symptoms (all, P < 0.001). Our findings revealed bilateral widespread pressure hypersensitivity in subjects with carpal tunnel syndrome, which suggest that widespread central sensitization is involved in patients with unilateral carpal tunnel syndrome. The generalized decrease in pressure pain thresholds associated with pain intensity and duration of symptoms supports a role of the peripheral drive to initiate and maintain central sensitization. Nevertheless, both central and peripheral sensitization mechanisms are probably involved at the same time in carpal tunnel syndrome.

  11. Mice with a deletion of the major central myelin protein exhibit hypersensitivity to noxious thermal stimuli: involvement of central sensitization.

    Science.gov (United States)

    Petit, Bérengère; Giraudet, Fabrice; Béchon, Céline; Bardin, Laurent; Avan, Paul; Boespflug-Tanguy, Odile; Bégou, Mélina

    2014-05-01

    Null mutations in the gene encoding the major myelin protein of the central nervous system, proteolipid protein 1 (PLP1), cause an X-linked form of spastic paraplegia (SPG2) associated with axonal degeneration. While motor symptoms are the best known manifestations of this condition, its somatosensory disturbances have been described but poorly characterized. We carried out a longitudinal study in an animal model of SPG2 - mice carrying a deletion of the Plp1 gene (Plp-null mice). Plp-null mice exhibited severe early-onset thermal hyperalgesia, in the absence of thermal allodynia. We first performed an electrophysiological testing which showed an early decrease in peripheral and spinal conduction velocities in Plp null mice. Such as the abnormal sensitive behaviors, this slowing of nerve conduction was observed before the development of myelin abnormalities at the spinal level, from 3months of age, and without major morphological defects in the sciatic nerve. To understand the link between a decrease in nerve velocity and an increased response to thermal stimuli before the appearance of myelin abnormalities, we focused our attention on the dorsal horn of the spinal cord, the site of integration of somatosensory information. Immunohistochemical studies revealed an early-onset activation of astrocytes and microglia that worsened with age, associated later in age with perturbation of the expression of the sensory neuropeptides calcitonin-gene-related peptide and galanin. Taken together, these results represent complementary data supporting the hypothesis that Plp-null mice suffer from ganglionopathy associated with late onset central demyelination but with few peripheral nerve alterations, induced by the glial-cell-mediated sensitization of the spinal cord. The mechanism suggested here could underlie pain experiments in other leukodystrophies as well as in other non-genetic demyelinating diseases such as multiple sclerosis. Copyright © 2014 Elsevier Inc. All rights

  12. CXCL1/CXCR2 signaling in pathological pain: Role in peripheral and central sensitization.

    Science.gov (United States)

    Silva, Rangel L; Lopes, Alexandre H; Guimarães, Rafaela M; Cunha, Thiago M

    2017-09-01

    Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is associated with plasticity of nociceptive pathway in which pain is prolonged even after healing of the injured tissue. Generally combinations of analgesic drugs are not sufficient to achieve selective palliation from chronic pain, besides causing a greater number of side effects. In order to identify novel alternatives for more effective treatments, it is necessary to clarify the underlying mechanisms of pathological pain. It is well established that there are two main components in pathological pain development and maintenance: (i) primary sensory neuron sensitization (peripheral sensitization), and (ii) central sensitization. In both components cytokines and chemokines act as key mediators in pain modulation. CXCL1 is a chemokine that promote both nociceptor and central sensitization via its main receptor CXCR2, which is a promising target for novel analgesic drugs. Here, we reviewed and discussed the role of the CXCL1/CXCR2 signaling axis in pathological pain conditions triggered by either peripheral inflammation or nerve injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Cuadrado, María L; López-de-Silanes, Carlos; Pareja, Juan A

    2011-03-01

    To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with cluster headache (CH). Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with CH. Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5-C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P < .001). A greater degree of sensitization over the mastoid process (P < .001) and a lower degree of sensitization over the tibialis anterior muscle (P < .01) was found. Our findings revealed bilateral widespread pressure pain hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition. © 2010 American Headache Society.

  14. Central sensitization in urogynecological chronic pelvic pain: a systematic literature review.

    Science.gov (United States)

    Kaya, Serap; Hermans, Linda; Willems, Tine; Roussel, Nathalie; Meeus, Mira

    2013-01-01

    Chronic pelvic pain (CPP) is a complex pain syndrome. Since its pathogenesis is still poorly understood and structural alterations in pain related brain regions may be present, there is a greater acceptance that sensitization of the central nervous system (CNS) plays an important role in the development and maintenance of chronicity. The purpose of this study is to systematically review the scientific evidence regarding central sensitization (CS) in female patients with urogynecological CPP. Systematic review of the literature. A systematic literature search was conducted in PubMed and Web of Science using different keyword combinations related to urogynecological CPP and central sensitization. Full text clinical reports addressing CS in adult women with urogynecological CPP were included and assessed for methodological quality by 2 independent reviewers. After screening for the eligibility, a total of 29 full-text articles with low to good methodological quality were retained. All studies were observational, 27 of which were case-control and 2 of which were cohorts. Sensitivity of the CNS was investigated by using a variety of methods. Although different central mechanisms seem to be involved in pain processing, the present evidence suggests hyperexcitability of the CNS in patients with urogynecological CPP. Altered brain morphology and function, generalized hyperalgesia to different type of stimuli, overactive bottom-up nociceptive mechanisms, and autonomic dysregulation were established in patients with urogynecological CPP. Nevertheless, diffuse noxious inhibitory control seemed normal, and therefore the contribution of an impaired endogenous pain inhibition mechanism to CPP requires further study. The same goes for the contribution of psychological factors. The level of evidence of retained studies is low due to the observational study designs and a wide range of diagnoses and assessment methods. Although the majority of the literature provides evidence for

  15. Central Sensitization in Functional Chronic Pain Syndromes: Overview and Clinical Application.

    Science.gov (United States)

    Bettini, Liz; Moore, Ki

    2016-10-01

    The purpose of this review and clinical application article is to offer nurses up-to-date knowledge on peripheral and central sensitization in chronic functional pain syndromes, and to discuss therapies that have shown efficacy in treating various aspects of these disorders. Central sensitization is a result of changes in the peripheral and central nervous system due to noxious stimuli, such as illness or trauma. Once these changes occur, treatment for the associated syndromes requires a multimodal approach that includes behavioral pain psychology, physical therapy, and pharmacological agents that specifically target neuroinflammation, pain modulation, and amplification of pain pathways. More research needs to be conducted on the basis and patient perception of functional pain syndromes to reduce the morbidity and significant disability associated with these illnesses. Nurses have the opportunity to be at the forefront of this research because of their holistic and multidimensional approach to patient care, assessment, and symptom management. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  16. Hyperbaric oxygen therapy attenuates central sensitization induced by a thermal injury in humans.

    Science.gov (United States)

    Rasmussen, V M; Borgen, A E; Jansen, E C; Rotbøll Nielsen, P H; Werner, M U

    2015-07-01

    Hyperbaric oxygen (HBO2 ) treatment has in animal experiments demonstrated antinociceptive effects. It was hypothesized that these effects would attenuate secondary hyperalgesia areas (SHAs), an expression of central sensitization, after a first-degree thermal injury in humans. Seventeen healthy volunteers were examined during two sessions using a randomized crossover design. Volunteers were studied during control conditions (ambient pressure, FI O2  = 0.21) and during HBO2 (2.4 standard atmosphere, FI O2  = 1.0, 90 min) conditions in a pressure chamber. Quantitative sensory testing, including assessment of SHAs was performed. A statistically significant overall attenuation of SHAs was seen during the HBO2 sessions compared with the control-sessions (P = 0.011). In the eight volunteers starting with the HBO2 session, no difference in SHAs compared with control was demonstrated. However, in the nine volunteers starting with the control session, a statistical significant attenuation of SHAs was demonstrated in the HBO2 session (P = 0.004). The results indicate that HBO2 therapy in humans attenuates central sensitization induced by a thermal skin injury, compared with control. These new and original findings in humans corroborate animal experimental data. The thermal injury model may give impetus to future human neurophysiological studies exploring the central effects of hyperbaric oxygen treatment. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. Design and optimization of stress centralized MEMS vector hydrophone with high sensitivity at low frequency

    Science.gov (United States)

    Zhang, Guojun; Ding, Junwen; Xu, Wei; Liu, Yuan; Wang, Renxin; Han, Janjun; Bai, Bing; Xue, Chenyang; Liu, Jun; Zhang, Wendong

    2018-05-01

    A micro hydrophone based on piezoresistive effect, "MEMS vector hydrophone" was developed for acoustic detection application. To improve the sensitivity of MEMS vector hydrophone at low frequency, we reported a stress centralized MEMS vector hydrophone (SCVH) mainly used in 20-500 Hz. Stress concentration area was actualized in sensitive unit of hydrophone by silicon micromachining technology. Then piezoresistors were placed in stress concentration area for better mechanical response, thereby obtaining higher sensitivity. Static analysis was done to compare the mechanical response of three different sensitive microstructure: SCVH, conventional micro-silicon four-beam vector hydrophone (CFVH) and Lollipop-shaped vector hydrophone (LVH) respectively. And fluid-structure interaction (FSI) was used to analyze the natural frequency of SCVH for ensuring the measurable bandwidth. Eventually, the calibration experiment in standing wave field was done to test the property of SCVH and verify the accuracy of simulation. The results show that the sensitivity of SCVH has nearly increased by 17.2 dB in contrast to CFVH and 7.6 dB in contrast to LVH during 20-500 Hz.

  18. Pliocene-Pleistocene (Nukumaruan) lithostratigraphy of the Tangoio block, and origin of sedimentary cyclicity, central Hawke's Bay, new Zealand

    International Nuclear Information System (INIS)

    Haywick, D.W.; Lowe, D.A.; Beu, A.G.; Henderson, R.A.; Carter, R.M.

    1991-01-01

    Eleven formations are defined within the Pliocene-Pleistocene Petane Group in a 450 km 2 uplifted area of central Hawkes Bay (Tangoio block). In ascending order these are: Waipunga Formation (new), Esk Formation, Tutira Formation (new), Aropaoanui Formation (new), Darkys Spur Formation (new), Mairau Formation (new), Tangoio Formation, Te Ngaru Formation, Waipatiki Formation, Devils Elbow Formation, and Kaiwaka Formation. Petane Group strata are cyclothemic and alternate between coarse-grained lithofacies (greywacke gravel, siliciclastic and carbonate sand/sandstone and bioclastic limestone) ascribed to nonmarine and inner shelf depositional environments, and sandy/muddy-silt ('papa') ascribed to mid-shelf deposition. The Petane Group is characterised by remarkable lateral continuity of formations, contrasting with conspicuous vertical changes. This stratigraphic style is consistent with glacio-eustatic sea-level fluctuations as proposed by Vella and Beu and Edwards, whereby coarse-grained lithofacies were deposited during sea-level low stands and fine-grained lithofacies were deposited during sea-level high stands. Foraminifera extracted from low-stand lithofacies display opposite δ 18 O signatures to that predicted for glacio-eustasy, a result of synsedimentary seawater dilution during sea-level low stands, and/or isotopic exchange during meteoric diagenesis. Stratigraphic and sedimentary criteria indicate that the Petane Group was deposited under unique circumstances of rapid basinal subsidence and a high rate of sedimentation. This offers an explanation for the general rarity of cyclothemic successions in the Pliocene-Pleistocene stratigraphic record. (author). 45 refs., 9 figs., 1 tab

  19. Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

    Science.gov (United States)

    Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

    2016-03-01

    Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest

  20. Protein Kinase C γ Contributes to Central Sensitization in a Rat Model of Chronic Migraine.

    Science.gov (United States)

    Wu, Baixue; Wang, Sha; Qin, Guangcheng; Xie, Jingmei; Tan, Ge; Zhou, Jiying; Chen, Lixue

    2017-10-01

    Protein kinase C γ (PKCγ) is a critical regulator of central sensitization and is widely recognized to be involved in the pathogenesis of chronic migraine (CM). However, the function of PKCγ in CM remains unknown. This study investigated the role of PKCγ on pathogenesis of CM. We repeated infusions of inflammatory soup (IS) on the intact dura of conscious rats to model recurrent trigeminovascular or dural nociceptor activation assumed to occur in patients with CM. The von Frey test was then used to detect changes in pain threshold. QT-PCR, western blotting, and double immunofluorescence staining were performed to detect the expression and location of PKCγ in the trigeminal nucleus caudalis (TNC) and the expressions of calcitonin gene-related peptide (CGRP), c-Fos, and phosphorylation level of GluR1 subunit at serine 831. Chelerythrine chloride (CHE) and phorbol 12-myristate 13-acetate (PMA) were administrated to investigate the role of PKCγ in central sensitization. We found that repeated infusions of IS induced mechanical allodynia. PKCγ was significantly increased in TNC after CM. Furthermore, inhibition of PKCγ by CHE relieved allodynia and reduced the expression of CGRP and c-Fos. Activation of PKCγ by PMA aggravated allodynia and increased the expression of CGRP and c-Fos. In addition, inhibition of PKCγ reduced the phosphorylation level of GluR1; in contrast, activation of PKCγ increased the phosphorylation level of GluR1. These results suggest PKCγ-induced GluR1 phosphorylation might participate in central sensitization in a rat model of CM. We suggest that PKCγ is a potential therapeutic target for CM.

  1. Validation of the Japanese version of the Central Sensitization Inventory in patients with musculoskeletal disorders.

    Science.gov (United States)

    Tanaka, Katsuyoshi; Nishigami, Tomohiko; Mibu, Akira; Manfuku, Masahiro; Yono, Satoko; Shinohara, Yoshikazu; Tanabe, Akihito; Ono, Rei

    2017-01-01

    Many musculoskeletal pain conditions are characterized by hypersensitivity, which is induced by central sensitization (CS). A questionnaire, the Central Sensitization Inventory (CSI), was recently developed to help clinicians identify patients whose presenting symptoms may be related to central sensitivity syndrome (CSS). The aims of the present study were to examine criterion validity and construct validity of the Japanese version of the CSI (CSI-J), and to investigate prevalence rates of CS severity levels in patients with musculoskeletal disorders. Translation of the CSI into Japanese was conducted using a forward-backward method. Two hundred and ninety patients with musculoskeletal pain disorders completed the resultant CSI-J. A subset of the patients (n = 158) completed the CSI-J again one week later. The relationships between CSI and clinical symptoms, EuroQol 5-dimension (EQ-5D) and Brief Pain Inventory (BPI), were examined for criterion validity. EQ-5D assesses Health-related QOL and BPI measures pain intensity and pain interference. The psychometric properties were evaluated with analyses of construct validity, factor structure and internal consistency, and subsequently investigate the prevalence rates of CS severity levels. The CSI-J demonstrated high internal consistency (Cronbach's α = 0.89) and test-retest reliability was excellent value (ICC = 0.85). The CSI-J was significantly correlated with EQ-5D (r = -0.44), pain intensity (r = 0.42), and pain interference (r = 0.48) (p < 0.01 for all). Ten percent of the participants were above the cutoff "40". The exploratory factor analysis resulted in 5-factor model. This study reported that the CSI-J was a useful and psychometrically sound tool to assess CSS in Japanese patients with musculoskeletal disorders. The finding of the prevalence rates of CS severity levels in patients with musculoskeletal disorders may help clinicians to decide strategy of treatment.

  2. Orai1 Plays a Crucial Role in Central Sensitization by Modulating Neuronal Excitability.

    Science.gov (United States)

    Dou, Yannong; Xia, Jingsheng; Gao, Ruby; Gao, Xinghua; Munoz, Frances M; Wei, Dongyu; Tian, Yuzhen; Barrett, James E; Ajit, Seena; Meucci, Olimpia; Putney, James W; Dai, Yue; Hu, Huijuan

    2018-01-24

    Pathological pain is a common and debilitating condition that is often poorly managed. Central sensitization is an important mechanism underlying pathological pain. However, candidate molecules involved in central sensitization remain unclear. Store-operated calcium channels (SOCs) mediate important calcium signals in nonexcitable and excitable cells. SOCs have been implicated in a wide variety of human pathophysiological conditions, including immunodeficiency, occlusive vascular diseases, and cancer. However, the role of SOCs in CNS disorders has been relatively unexplored. Orai1, a key component of SOCs, is expressed in the human and rodent spinal cord dorsal horn, but its functional significance in dorsal horn neurons is poorly understood. Here we sought to explore a potential role of Orai1 in the modulation of neuronal excitability and A-type potassium channels involved in pain plasticity. Using both male and female Orai1 knock-out mice, we found that activation of Orai1 increased neuronal excitability and reduced A-type potassium channels via the protein kinase C-extracellular signal-regulated protein kinase (PKC-ERK) pathway in dorsal horn neurons. Orai1 deficiency significantly decreased acute pain induced by noxious stimuli, nearly eliminated the second phase of formalin-induced nociceptive response, markedly attenuated carrageenan-induced ipsilateral pain hypersensitivity and abolished carrageenan-induced contralateral mechanical allodynia. Consistently, carrageenan-induced increase in neuronal excitability was abolished in the dorsal horn from Orai1 mutant mice. These findings uncover a novel signaling pathway involved in the pain process and central sensitization. Our study also reveals a novel link among Orai1, ERK, A-type potassium channels, and neuronal excitability. SIGNIFICANCE STATEMENT Orai1 is a key component of store-operated calcium channels (SOCs) in many cell types. It has been implicated in such pathological conditions as immunodeficiency

  3. Theoretical perspectives on central chemosensitivity: CO2/H+-sensitive neurons in the locus coeruleus.

    Directory of Open Access Journals (Sweden)

    Maria C Quintero

    2017-12-01

    Full Text Available Central chemoreceptors are highly sensitive neurons that respond to changes in pH and CO2 levels. An increase in CO2/H+ typically reflects a rise in the firing rate of these neurons, which stimulates an increase in ventilation. Here, we present an ionic current model that reproduces the basic electrophysiological activity of individual CO2/H+-sensitive neurons from the locus coeruleus (LC. We used this model to explore chemoreceptor discharge patterns in response to electrical and chemical stimuli. The modeled neurons showed both stimulus-evoked activity and spontaneous activity under physiological parameters. Neuronal responses to electrical and chemical stimulation showed specific firing patterns of spike frequency adaptation, postinhibitory rebound, and post-stimulation recovery. Conversely, the response to chemical stimulation alone (based on physiological CO2/H+ changes, in the absence of external depolarizing stimulation, showed no signs of postinhibitory rebound or post-stimulation recovery, and no depolarizing sag. A sensitivity analysis for the firing-rate response to the different stimuli revealed that the contribution of an applied stimulus current exceeded that of the chemical signals. The firing-rate response increased indefinitely with injected depolarizing current, but reached saturation with chemical stimuli. Our computational model reproduced the regular pacemaker-like spiking pattern, action potential shape, and most of the membrane properties that characterize CO2/H+-sensitive neurons from the locus coeruleus. This validates the model and highlights its potential as a tool for studying the cellular mechanisms underlying the altered central chemosensitivity present in a variety of disorders such as sudden infant death syndrome, depression, and anxiety. In addition, the model results suggest that small external electrical signals play a greater role in determining the chemosensitive response to changes in CO2/H+ than previously

  4. Cheat-sensitive commitment of a classical bit coded in a block of m × n round-trip qubits

    Science.gov (United States)

    Shimizu, Kaoru; Fukasaka, Hiroyuki; Tamaki, Kiyoshi; Imoto, Nobuyuki

    2011-08-01

    This paper proposes a quantum protocol for a cheat-sensitive commitment of a classical bit. Alice, the receiver of the bit, can examine dishonest Bob, who changes or postpones his choice. Bob, the sender of the bit, can examine dishonest Alice, who violates concealment. For each round-trip case, Alice sends one of two spin states |S±⟩ by choosing basis S at random from two conjugate bases X and Y. Bob chooses basis C ∈ {X,Y} to perform a measurement and returns a resultant state |C±⟩. Alice then performs a measurement with the other basis R (≠S) and obtains an outcome |R±⟩. In the opening phase, she can discover dishonest Bob, who unveils a wrong basis with a faked spin state, or Bob can discover dishonest Alice, who infers basis C but destroys |C±⟩ by setting R to be identical to S in the commitment phase. If a classical bit is coded in a block of m × n qubit particles, impartial examinations and probabilistic security criteria can be achieved.

  5. Cheat-sensitive commitment of a classical bit coded in a block of mxn round-trip qubits

    International Nuclear Information System (INIS)

    Shimizu, Kaoru; Fukasaka, Hiroyuki; Tamaki, Kiyoshi; Imoto, Nobuyuki

    2011-01-01

    This paper proposes a quantum protocol for a cheat-sensitive commitment of a classical bit. Alice, the receiver of the bit, can examine dishonest Bob, who changes or postpones his choice. Bob, the sender of the bit, can examine dishonest Alice, who violates concealment. For each round-trip case, Alice sends one of two spin states |S±> by choosing basis S at random from two conjugate bases X and Y. Bob chooses basis C is an element of {X,Y} to perform a measurement and returns a resultant state |C±>. Alice then performs a measurement with the other basis R (≠S) and obtains an outcome |R±>. In the opening phase, she can discover dishonest Bob, who unveils a wrong basis with a faked spin state, or Bob can discover dishonest Alice, who infers basis C but destroys |C±> by setting R to be identical to S in the commitment phase. If a classical bit is coded in a block of mxn qubit particles, impartial examinations and probabilistic security criteria can be achieved.

  6. Cheat-sensitive commitment of a classical bit coded in a block of mxn round-trip qubits

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Kaoru; Fukasaka, Hiroyuki [NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato-Wakamiya, Atsugi, Kanagawa 243-0198 (Japan); Tamaki, Kiyoshi [NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato-Wakamiya, Atsugi, Kanagawa 243-0198 (Japan); National Institute of Information and Communications Technology (NICT), 4-2-1 Nukui-kitamachi, Koganei, Tokyo 184-8795 (Japan); Imoto, Nobuyuki [Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka 560-8531 (Japan)

    2011-08-15

    This paper proposes a quantum protocol for a cheat-sensitive commitment of a classical bit. Alice, the receiver of the bit, can examine dishonest Bob, who changes or postpones his choice. Bob, the sender of the bit, can examine dishonest Alice, who violates concealment. For each round-trip case, Alice sends one of two spin states |S{+-}> by choosing basis S at random from two conjugate bases X and Y. Bob chooses basis C is an element of {l_brace}X,Y{r_brace} to perform a measurement and returns a resultant state |C{+-}>. Alice then performs a measurement with the other basis R ({ne}S) and obtains an outcome |R{+-}>. In the opening phase, she can discover dishonest Bob, who unveils a wrong basis with a faked spin state, or Bob can discover dishonest Alice, who infers basis C but destroys |C{+-}> by setting R to be identical to S in the commitment phase. If a classical bit is coded in a block of mxn qubit particles, impartial examinations and probabilistic security criteria can be achieved.

  7. Improving the photovoltaic parameters in Quantum dot sensitized solar cells through employment of chemically deposited compact titania blocking layer

    Energy Technology Data Exchange (ETDEWEB)

    Rajendra Prasad, M.B., E-mail: rajendraprasadmb75@gmail.com [Advanced Physics Laboratory, Department of Physics, SavitibaiPhule Pune University, Pune, 411007 (India); National Defence Academy, Khadakwasla, Pune, 411023 (India); Kadam, Vishal [Advanced Physics Laboratory, Department of Physics, SavitibaiPhule Pune University, Pune, 411007 (India); Joo, Oh-Shim [Korea Institute of Science and Technology, PO Box No. 131, Chongryang, Seoul, 130-650 (Korea, Republic of); Pathan, Habib M. [Advanced Physics Laboratory, Department of Physics, SavitibaiPhule Pune University, Pune, 411007 (India)

    2017-06-15

    Incorporation of compact blocking layer at the Transparent Conducting Oxide (TCO)/Electrolyte interface is an effective method to improve the device performance in QDSSC through mitigation of electron recombinations at this interface. This paper reports the most facile and cost effective method of depositing a rutile titania Compact Layer (CL) over Fluorine doped Tin Oxide (FTO) substrate and its application in titania based CdS QD sensitized solar cells. The deposited compact layers are characterized to study their structural, optical, morphological and electrochemical properties using X-Ray Diffractometry, UV–Visible spectroscopy, Scanning electron microscopy, Cyclic Voltammetry and Contact Angle measurements. Sandwich solar cells are fabricated using these CL based electrodes and characterized using Electrochemical Impedance Spectroscopy, Open Circuit Voltage Decay and J-V characteristics. The CL incorporated CdS QDSSC showed more than 100% increase in the photoconversion efficiency (1.68%) as compared to its bare FTO counterpart (0.73%) proving the efficacy of employed strategy. - Highlights: • Deposited titania compact layer by a facile room temperature chemical bath method. • Employed this to mitigate back electron transfer at TCO/Electrolyte interface. • Compact layer incorporation has improved the solar cell performance by 130%.

  8. Tetraethylammonium-sensitive K(+) current in the bovine spermatozoa and its blocking by the venom of the Chilean Latrodectus mactans.

    Science.gov (United States)

    Parodi, Jorge; Navarrete, Patricia; Marconi, Marcelo; Gutiérrez, Raúl Sánchez; Martínez-Torres, Ataúlfo; Mejías, Fernando Romero

    2010-02-01

    The morphology and size of spermatozoa hinder the study of the functional properties of the spermatozoa plasma membrane. However, some studies have revealed the presence of a number of ion channels in this cell. We set out to measure the endogenous currents and to study the effect of the venom of the Chilean black widow spider (Latrodectus mactans). By patch-clamping bovine spermatozoa our results indicate the presence of an outwardly rectifying current, sensitive to changes in K(+) concentration (30-140 mM) and to tetraethylammonium (TEA, 10-100 mM). The application of the venom (7.5 microg/ml) blocks these K+ currents and then alters the passive properties of the plasma membrane. This leads to the entry of Ca(++), reflected by a change in basal fluorescent units (5+/-2 at 35+/-10 FAU). The Ca(++) influx follows a reduction in the membrane conductance (control 22+/-2; venom 10+/-1 pS), as calcium channels open in accord with voltage dependence.

  9. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: M_MAMMAL (Marine Mammal Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for dolphins, porpoises, whales, seals, sea lions, and sea otters in Central California. Vector polygons in...

  10. Environmental Sensitivity Index (ESI) Atlas: Central California (Including Monterey Bay Sanctuary), maps and geographic information systems data (NODC Accession 0013176)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Environmental Sensitivity Index (ESI) maps have been developed for the coastal areas of Central California from Point Conception to Point Reyes National Seashore....

  11. Recognition and Treatment of Central Sensitization in Chronic Pain Patients: Not Limited to Specialized Care.

    Science.gov (United States)

    Nijs, Jo; Goubert, Dorien; Ickmans, Kelly

    2016-12-01

    Modern pain neuroscience has substantially improved our understanding of the (development of) chronic musculoskeletal pain. The time has come for orthopaedic and sports physical therapists to implement modern pain neuroscience in specialized, but definitely also in primary, care settings, including the role of central sensitization (CS) in amplifying and explaining the presence of the pain experience. Central sensitization dominates the clinical picture in a subgroup of the musculoskeletal pain population, ranging from tennis elbow over shoulder pain to osteoarthritis and whiplash. Applying modern pain neuroscience to clinical practice implies (1) recognizing those patients having predominant CS pain, and (2) accounting for CS when designing the treatment plan in those with predominant CS pain. Future work in this area should (1) examine the validity of the proposed clinical classification algorithm for identifying CS pain in patients with orthopaedic and sports injuries, and (2) explore evidence-based treatment options for patients having predominant CS pain. J Orthop Sports Phys Ther 2016;46(12):1024-1028. doi:10.2519/jospt.2016.0612.

  12. Painful temporomandibular disorders and central sensitization: implications for management-a pilot study.

    Science.gov (United States)

    Campi, L B; Jordani, P C; Tenan, H L; Camparis, C M; Gonçalves, D A G

    2017-01-01

    The objective was to investigate the presence of cutaneous allodynia and hyperalgesia in the trigeminal and extra-trigeminal areas, as a surrogate for central sensitization (CS), in women with a painful temporomandibular disorder (TMD) and without other painful conditions. Painful TMDs, depression, and non-specific physical symptoms (NSPS) were classified according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The amount of pain in the trigeminal and extra-trigeminal areas was determined using a visual analogue scale (0-100mm) after the application of a vibrotactile stimulus and assessment of the pressure pain threshold (PPT). Statistical tests (Fisher's, χ 2 , and Mann-Whitney) were performed, with a significance level of 5%. The sample comprised 45 women (mean age 37.5 years; 16 with a painful TMD) who were free of any headache, fibromyalgia, or other painful condition. Painful TMD was associated with higher pain sensitivity and lower PPT values in the trigeminal (Psensitivity. The presence of hyperalgesia and allodynia in both the trigeminal and extra-trigeminal regions among women with a painful TMD indicated the presence of CS. Changes involving the central nervous system should be considered during the evaluation and management of patients with a painful TMD. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Transient inhibition of LIMKs significantly attenuated central sensitization and delayed the development of chronic pain.

    Science.gov (United States)

    Yang, Xiangyu; He, Guiqin; Zhang, Xiaoyun; Chen, Lu; Kong, Yue; Xie, Wei; Jia, Zhengping; Liu, Wen-Tao; Zhou, Zikai

    2017-10-01

    Central sensitization represents a key mechanism mediating chronic pain, a major clinical problem lacking effective treatment options. LIM-domain kinases (LIMKs) selectively regulate several substrates, e.g. cofilin and cAMP response element-binding protein (CREB), that profoundly affect neural activities, such as synaptogenesis and gene expression, thus critical in the consolidation of long-term synaptic potentiation and memory in the brain. In this study, we demonstrate that LIMK deficiency significantly impaired the development of multiple forms of chronic pain. Mechanistic studies focusing on spared nerve injury (SNI) model reveal a pivotal role of LIMKs in the up-regulation of spontaneous excitatory synaptic transmission and synaptogenesis after pain induction. Depending on the pain induction methods, LIMKs can be transiently activated with distinct time courses. Accordingly, pharmacological inhibition of LIMKs targeting this critical period remarkably attenuated central sensitization in the spinal cord and alleviated pain behaviors. We propose selectively targeting LIMKs during their activation phase as a potential therapeutic strategy for clinical management of chronic pain, especially for chronic pain with predictable onset and development time courses, such as chronic post-surgical pain (PSP). Copyright © 2017. Published by Elsevier Ltd.

  14. Nicotine stimulates expression of proteins implicated in peripheral and central sensitization.

    Science.gov (United States)

    Hawkins, J L; Denson, J E; Miley, D R; Durham, P L

    2015-04-02

    Pain patients who are nicotine dependent report a significantly increased incidence and severity of pain intensity. The goal of this study was to determine the effects of prolonged nicotine administration on inflammatory proteins implicated in the development of peripheral and central sensitization of the trigeminal system. Behavioral, immunohistochemical, and microarray studies were utilized to investigate the effects of nicotine administered daily for 14 days via an Alzet® osmotic pump in Sprague Dawley rats. Systemic nicotine administration caused a significant increase in nocifensive withdrawals to mechanical stimulation of trigeminal neurons. Nicotine stimulated expression of the pro-inflammatory signal transduction proteins phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-c-Jun N-terminal kinase (p-JNK), and protein kinase A (PKA) in the spinal trigeminal nucleus. Nicotine also promoted elevations in the expression of glial fibrillary acidic protein (GFAP), a biomarker of activated astrocytes, and the microglia biomarker ionized calcium-binding adapter molecule 1 (Iba1). Similarly, levels of eleven cytokines were significantly elevated with the largest increase in expression of TNF-α. Levels of PKA, p-ERK, and p-JNK in trigeminal ganglion neurons were increased by nicotine. Our findings demonstrate that prolonged systemic administration of nicotine promotes sustained behavioral and cellular changes in the expression of key proteins in the spinal trigeminal nucleus and trigeminal ganglion implicated in the development and maintenance of peripheral and central sensitization. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Central Sensitization of Mechanical Nociceptive Pathways Is Associated with a Long-Lasting Increase of Pinprick-Evoked Brain Potentials.

    Science.gov (United States)

    van den Broeke, Emanuel N; Lambert, Julien; Huang, Gan; Mouraux, André

    2016-01-01

    Intense or sustained nociceptor activation, occurring, for example, after skin injury, can induce "central sensitization," i.e., an increased responsiveness of nociceptive neurons in the central nervous system. A hallmark of central sensitization is increased mechanical pinprick sensitivity in the area surrounding the injured skin. The aim of the present study was to identify changes in brain activity related to this increased pinprick sensitivity. In 20 healthy volunteers, increased pinprick sensitivity was induced using high frequency electrical stimulation of the forearm skin (HFS). Mechanical pinprick stimulation (64 and 90 mN) was used to elicit event-related brain potentials (ERPs). The recordings were performed before, 20 min after and 45 min after applying HFS. The contralateral non-sensitized arm served as control. Pinprick stimulation of 64 mN, but not 90 mN, applied in the area of increased pinprick sensitivity elicited a significant increase of a late-latency positive wave, between 300 and 1100 ms after stimulus onset and was maximal at midline posterior electrodes. Most importantly, this increase in EEG activity followed the time course of the increase in pinprick perception, both being present 20 and 45 min after applying HFS. Our results show that the central sensitization of mechanical nociceptive pathways, manifested behaviorally as increased pinprick sensitivity, is associated with a long-lasting increase in pinprick-evoked brain potentials provided that a 64 mN stimulation intensity is used.

  16. Editorial review: an update on central sensitivity syndromes and the issues of nosology and psychobiology.

    Science.gov (United States)

    Yunus, Muhammad B

    2015-01-01

    Central sensitization (CS), simply defined as an amplified response of the central nervous system to peripheral input, is a concept of great importance in clinical medicine. It has helped to explain aspects of the pathophysiology of common diseases, e.g. fibromyalgia syndrome (FMS), irritable bowel syndrome, vulvodynia, headaches, chronic pelvic pain and other overlapping conditions (collectively called central sensitivity syndromes, or CSS). It also applies to pain of complex regional pain syndrome, osteoarthritis (OA), rheumatoid arthritis (RA) and post-operative pain. The pathology-pain gap in CSS is readily explained by CS. Many FMS and other CSS patients have peripheral pathology, e.g. nociceptive areas in the muscles, arthritis, small fiber neuropathy and inflammation. Pro-inflammatory cytokines are elevated in some patients. Identification of CS in patients with structural pathology, e.g. OA and RA, has helped to explain why not all patients benefit from nonsteroidal anti-inflammatory drugs or joint replacement surgery, and require therapy directed at CS. Glial cells are important in pain processing. Remarkable advances have been achieved in neuroimaging, including visualization of grey matter and white matter, not only during provoked pain but also pain at rest. Based on CS mechanisms, targeted individual therapy may now be possible. Appropriate nosology is important particularly for effective patient care. Dichotomy of neurochemical-structural ("functional") and structural ("organic") pathology should be abandoned; many patients have both. Psychobiology is also biology. Patient-blaming terms like somatization, somatizer and catastrophizing should be avoided. For therapy, both pharmacological and non- pharmacological approaches are important, including recognition of subgroups and person/patient-centered care.

  17. Dimensionality and Reliability of the Central Sensitization Inventory in a Pooled Multicountry Sample.

    Science.gov (United States)

    Cuesta-Vargas, Antonio I; Neblett, Randy; Chiarotto, Alessandro; Kregel, Jeroen; Nijs, Jo; van Wilgen, C Paul; Pitance, Laurent; Knezevic, Aleksandar; Gatchel, Robert J; Mayer, Tom G; Viti, Carlotta; Roldan-Jiménez, Cristina; Testa, Marco; Caumo, Wolnei; Jeremic-Knezevic, Milica; Luciano, Juan V

    2018-03-01

    Central sensitization (CS) involves the amplification of neural signaling within the central nervous system, which evokes pain hypersensitivity. The Central Sensitization Inventory (CSI) assesses 25 overlapping health-related symptom dimensions that have been reported to be associated with CS-related disorders. Previous studies have reported satisfactory test-retest reliability and internal consistency, but factor analyses have exhibited conflicting results in different language versions. The purpose of this cross-sectional study was to thoroughly examine the dimensionality and reliability of the CSI, with pooled data from 1,987 individuals, collected in several countries. The principal component analysis suggested that 1 general factor of CS best described the structure. A subsequent confirmatory factor analysis revealed that a bifactor model, which accounted for the covariance among CSI items, with regard to 1 general factor and 4 orthogonal factors, fit the CSI structure better than the unidimensional and the 4-factor models. Additional analyses indicated substantial reliability for the general factor (ie, Cronbach α = .92; ω = .95; and ω hierarchical = .89). Reliability results for the 4 specific factors were considered too low to be used for subscales. The results of this study clearly suggest that only total CSI scores should be used and reported. As far as we know, this is the first study that has examined the factor structure and reliability of the CSI in a large multicountry sample. The CSI is currently considered the leading self-report measure of CS-related symptoms worldwide. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Leysen, Laurence; Adriaenssens, Nele; Aguilar Ferrándiz, Maria Encarnación; Devoogdt, Nele; Tassenoy, An; Ickmans, Kelly; Goubert, Dorien; van Wilgen, C Paul; Wijma, Amarins J; Kuppens, Kevin; Hoelen, Wouter; Hoelen, Astrid; Moloney, Niamh; Meeus, Mira

    2016-06-01

    In addition to fatigue, pain is the most frequent persistent symptom in cancer survivors. Clear guidelines for both the diagnosis and treatment of pain in cancer survivors are lacking. Classification of pain is important as it may facilitate more specific targeting of treatment. In this paper we present an overview of nociceptive, neuropathic and central sensitization pain following cancer treatment, as well as the rationale, criteria and process for stratifying pain classification. Recently, a clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain was developed, based on a large body of research evidence and international expert opinion. We, a team of 15 authors from 13 different centers, four countries and two continents have applied this classification algorithm to the cancer survivor population. The classification of pain following cancer treatment entails two steps: (1) examining the presence of neuropathic pain; and (2) using an algorithm for differentiating predominant nociceptive and central sensitization pain. Step 1 builds on the established criteria for neuropathic pain diagnosis, while Step 2 applies a recently developed clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain to the cancer survivor population. The classification criteria allow identifying central sensitization pain following cancer treatment. The recognition of central sensitization pain in practice is an important development in the integration of pain neuroscience into the clinic, and one that is relevant for people undergoing and following cancer treatment.

  19. Hospitalizations due to primary care-sensitive cardiovascular conditions in municipalities of Central-West Brazil.

    Science.gov (United States)

    Batista, Sandro Rogério Rodrigues; Jardim, Paulo César Brandão Veiga; Sousa, Ana Luiza Lima; Salgado, Cláudia Maria

    2012-02-01

    To analyze rates of hospitalization due to primary care-sensitive cardiovascular conditions. This ecological study on 237 municipalities in the state of Goiás, Central-West Brazil, between 2000 and 2008, used data from the Hospital Information System and the Primary Care Information System. The hospitalization rates were calculated as the ratio between the number of hospitalizations due to cardiovascular conditions and the population over the age of 40 years. The data were evaluated over the three-year periods A (2000-2002), B (2003-2005) and C (2006-2008), according to sex, age group, population size, whether the individual belonged to the metropolitan region, healthcare macroregion, distance from the state capital, living conditions index and coverage within the Family Health Strategy. The potential population coverage of the Family Health Strategy was calculated in accordance with Ministry of Health guidelines. The variability of the rates was evaluated using the t test and ANOVA. A total of 253,254 hospitalizations (17.2%) occurred due to primary care-sensitive cardiovascular conditions. The hospitalization rates diminished between the three-year periods: A (213.5, SD = 104.6), B (199.7, SD = 96.3) and C (150.2, SD = 76.1), with differences from A to C and from B to C (p Conditions Index, there were decreases in the rates (p care-sensitive cardiovascular conditions decreased in these municipalities, independent of the Family Health Strategy coverage.

  20. Antibiotic sensitivity of escherichia coli isolated from urinary tract infection referred to Kermanshah central laboratory

    Directory of Open Access Journals (Sweden)

    Parviz Mohajeri

    2011-03-01

    Full Text Available Background: Escherichia coli (Ecoli has been considered as the most common agent of urinary tract infection in all regions. Recently, increased drug resistance has been lead to some problems in treatment related diseases. So, evaluation of resistance patterns of bacteria in each region could be a valuable guide for empirical treatment.Methods: All referred urine sample to Kermanshah Central Laboratory during 1998 that was reported positive to Ecoli were assessed. Susceptibility pattern to 19 antimicrobial agents was evaluated using Kirby Bauer method according to CLSI standards.Results: A total of 834 Ecoli isolated from 19,208 positive urine cultures. 84% of subjects were females and 16% males. Sensitivity rate for nitrofurantoin (84%, ceftizoxime (72%, norfloxacin (70%, cefotaxime (69%, Amikacin (66%, ciprofloxacin (65%, ceftriaxone (64%, ceftazidim (55% was higher than 50%. Sensitivity to nalidixic acid, cefexime, gentamicin, co-trimoxazole, ticarcillin, caphalexin, cephalotin, tetracycline, amoxicillin, amoxicillin clavulanate and ampicillin were determined less than 50%.Conclusion: Nitrofurantoin and ceftizoxime are currently effective against Ecoli, although an indiscriminate use of antibiotics should be avoided because of drug resistance probable. It seems that ampicillin could be excluded from routine sensitivity testing.

  1. Central sleep apnea is associated with blunted baroreflex sensitivity in patients with myocardial infarction.

    Science.gov (United States)

    Strassburg, Alan; Majunke, Benina; Nötges, Jana K; Ortak, Jasmin; Kothe, Henning; Weitz, Gunther; Schunkert, Heribert; Bonnemeier, Hendrik

    2008-06-06

    The purpose of this study was to investigate the association of central sleep apnea (CSA) and baroreflex sensitivity (BRS) after acute myocardial infarction. Both, CSA and blunted BRS have been shown to be independent predictors for cardiovascular mortality in patients with heart failure. But in contrast to BRS, which has been extensively studied in the setting of AMI, the incidence of CSA in patients recovering from AMI is thus far unknown. As previous reports suggested a potential role of sleep apnoea in augmenting reflex autonomic modulation, we hypothesized that there is a strong interrelation between CSA and BRS. Seventeen male patients in the subacute phase of a first uncomplicated ST-segment elevation AMI and eight healthy male controls without evidence of coronary artery disease underwent polysomnography with simultaneous beat-to-beat ECG- and blood-pressure recordings. Sleep stage specific spontaneous BRS was calculated from blood pressure and RR-interval fluctuations by using the time domain sequential technique. AMI patients revealed to have a higher incidence and longer duration of central apnoeas in all sleep stages, light sleep, deep sleep and dream sleep. There were no significant sleep stage specific differences regarding BRS between groups, however, AMI patients with central sleep apnea exhibited blunted BRS which was inversely correlated to incidences of central apnea in all sleep stages. Our findings suggest a direct relationship between impaired BRS and repetitive occurrence of CSA by inverse correlation in all sleep stages in the subacute phase of AMI. Thus, reflex cardiac autonomic nervous control, being represented by the BRS, may be the link between CSA and prognosis.

  2. Sensitization study of dogs with atopic dermatitis in the central region of Rio Grande do Sul

    Directory of Open Access Journals (Sweden)

    D.T. Pereira

    2015-12-01

    Full Text Available Canine atopic dermatitis (CAD is a common dermatosis, defined as a genetic-related disease which predisposes to skin inflammation and pruritus, associated to a IgE-specific response in most of cases. Clinical diagnosis may be later complemented by skin allergy and/or serological tests. The aim of these tests is to identify possible allergens in order to enable the clinicians to select candidate antigens for allergen specific immunotherapy. In the present study 58 CAD positive animals were tested. All were submitted to the intradermal test (IDT and screened for the presence of antibodies against different antigens using ELISA. The obtained results show a high prevalence of sensitization among the tested dogs to house dust mites and to pollen ofC. dactylon. With this work it was possible to identify the main allergens involved in immunological response of dogs with CAD living in central area of Rio Grande do Sul.

  3. Central sensitization and perceived indoor climate among workers with chronic upper-limb pain

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus D.; Brandt, Mikkel

    2015-01-01

    threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain......Monitoring of indoor climate is an essential part of occupational health and safety. While questionnaires are commonly used for surveillance, not all workers may perceive an identical indoor climate similarly. The aim of this study was to evaluate perceived indoor climate among workers with chronic...... pain compared with pain-free colleagues and to determine the influence of central sensitization on this perception. Eighty-two male slaughterhouse workers, 49 with upper-limb chronic pain and 33 pain-free controls, replied to a questionnaire with 13 items of indoor climate complaints. Pressure pain...

  4. Primary headaches in patients with temporomandibular disorders: Diagnosis and treatment of central sensitization pain.

    Science.gov (United States)

    Sagripanti, Marco; Viti, Carlotta

    2017-07-28

    Central sensitization (CS) has been found in patients with temporomandibular disorders (TMD), craniofacial pain (CP) and primary headaches, but its clinical implications remain uncertain. The first aim was to provide a synthesis of the current state of knowledge about the link between CS and TMD associated with primary headaches; the second goal was to find methodologies to assess and treat CS in this subgroup of patients. A narrative review of the literature was conducted. CS is described in literature as an aggravating factor in patients with TMD-related primary headaches. Further studies are required to support this assertion. The importance of excluding chronic neuropathic pain and recognizing CS as the main component using a top-down approach to target the best pharmacological and non-pharmacological treatments is evident. Some useful tools to discriminate patients with CS from others have become available, but more research is required to enable an appropriate diagnosis.

  5. Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.

    Science.gov (United States)

    Liang, M; Lee, M C; O'Neill, J; Dickenson, A H; Iannetti, G D

    2016-08-01

    Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. Copyright © 2016 the American Physiological Society.

  6. Cross-Cultural Adaptation and Psychometric Validation of the Serbian Version of the Central Sensitization Inventory.

    Science.gov (United States)

    Knezevic, Aleksandar; Neblett, Randy; Jeremic-Knezevic, Milica; Tomasevic-Todorovic, Snezana; Boskovic, Ksenija; Colovic, Petar; Cuesta-Vargas, Antonio

    2017-08-04

    It has been increasingly recognized that many chronic pain conditions are associated with central sensitization (CS). The Central Sensitization Inventory (CSI) is a potentially useful tool for screening patients whose presenting symptoms are suspected of being related to CS, so that additional diagnostic evaluation can be performed and appropriate treatment can be initiated. The original English version is currently not available in Serbian. The CSI was translated into Serbian (CSI-Serb) and then psychometrically evaluated in a sample of 363 chronic pain subjects. The CSI-Serb showed a high degree of internal consistency (Cronbach's α = 0.909), excellent test-retest reliability (intraclass correlation coefficient type 2.1 = 0.947), and a significant goodness of fit test result (χ 2  = 888.44; P < 0.001). A factor analysis confirmed a 4-factor solution, as found by the original authors of the CSI, with all items retained. Higher CSI-Serb scores were associated with higher pain severity and longer pain duration. Total CSI scores distinguished between 3 subject groups with presumably different levels of CS, including fibromyalgia (53.3, SD = 11.2), chronic regional pain only (29.7, SD = 11.6), and a pain-free control group (20.9, SD = 9.1). The results of the present study indicate strong psychometric properties, including evidence of convergent and discriminant validity, of the CSI-Serb. These results correspond with those of other translated versions of the CSI that have been psychometrically evaluated and published. Due to the current interest in CS, and its relationship with many chronic pain conditions, it is anticipated that the CSI-Serb will benefit Serbian-speaking clinicians in the evaluation of patients with chronic pain conditions. © 2017 World Institute of Pain.

  7. The Vector Vortex Coronagraph: Sensitivity to Low-Order Aberrations, Central Obscuration, Chromaticism, and Polarization

    Science.gov (United States)

    Mawet, Dimitri; Pueyo, Laurent; Moody, Dwight; Krist, John; Serabyn, Eugene

    2010-01-01

    The Vector Vortex Coronagraph is a phase-based coronagraph, one of the most efficient in terms of inner working angle, throughput, discovery space, contrast, and simplicity. Using liquid-crystal polymer technology, this new coronagraph has recently been the subject of lab demonstrations in the near-infrared, visible and was also used on sky at the Palomar observatory in the H and K bands (1.65 and 2.2 micrometers, respectively) to image the brown dwarf companion to HR 7672, and the three extasolar planets around HR 8799. However, despite these recent successes, the Vector Vortex Coronagraph is, as are most coronagraphs, sensitive to the central obscuration and secondary support structures, low-order aberrations (tip-tilt, focus, etc), bandwidth (chromaticism), and polarization when image-plane wavefront sensing is performed. Here, we consider in detail these sensitivities as a function of the topological charge of the vortex and design properties inherent to the manufacturing technology, and show that in practice all of them can be mitigated to meet specific needs.

  8. Sustained nociceptive mechanical stimulation of latent myofascial trigger point induces central sensitization in healthy subjects.

    Science.gov (United States)

    Xu, Yi-Meng; Ge, Hong-You; Arendt-Nielsen, Lars

    2010-12-01

    The aim of the study is to test if sustained nociceptive mechanical stimulation (SNMS) of latent myofascial trigger points (MTrPs) induces widespread mechanical hyperalgesia. SNMS was obtained by inserting and retaining an intramuscular electromyographic (EMG) needle within a latent MTrP or a nonMTrP in the finger extensor muscle for 8 minutes in 12 healthy subjects. Pain intensity (VAS) and referred pain area induced by SNMS were recorded. Pressure pain threshold (PPT) was measured immediately before and after, and 10-, 20-, and 30-minutes after SNMS at the midpoint of the contralateral tibialis anterior muscle. Surface and intramuscular EMG during SNMS were recorded. When compared to nonMTrPs, maximal VAS and the area under VAS curve (VASauc) were significantly higher and larger during SNMS of latent MTrPs (both, P induction of local and referred pain. This study shows that MTrPs are one of the important peripheral pain generators and initiators for central sensitization. Therapeutic methods for decreasing the sensitivity and motor-unit excitability of MTrPs may prevent the development of muscle cramps and thus decrease local and referred pain. Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

  9. Objective validation of central sensitization in the rat UVB and heat rekindling model.

    Science.gov (United States)

    Weerasinghe, N S; Lumb, B M; Apps, R; Koutsikou, S; Murrell, J C

    2014-09-01

    The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model. The UVB/HR model was induced on the heel of the hind paw under anaesthesia. Mechanical withdrawal thresholds (MWTs) were obtained from biceps femoris EMG responses to a gradually increasing pinch at the mid hind paw region under alfaxalone anaesthesia, 96 h after UVB irradiation. MWT was compared between UVB/HR and SHAM-treated rats (anaesthetic only). Underlying central mechanisms in the model were pharmacologically validated by MWT measurement following intrathecal N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, or saline. Secondary hyperalgesia was confirmed by a significantly lower pre-drug MWT {mean [±standard error of the mean (SEM)]} in UVB/HR [56.3 (±2.1) g/mm(2) , n = 15] compared with SHAM-treated rats [69.3 (±2.9) g/mm(2) , n = 8], confirming face validity of the model. Predictive validity was demonstrated by the attenuation of secondary hyperalgesia by MK-801, where mean (±SEM) MWT was significantly higher [77.2 (±5.9) g/mm(2) n = 7] in comparison with pre-drug [57.8 (±3.5) g/mm(2) n = 7] and saline [57.0 (±3.2) g/mm(2) n = 8] at peak drug effect. The occurrence of central sensitization confirmed construct validity of the UVB/HR model. This study used objective outcome measures of secondary hyperalgesia to validate the rat UVB/HR model as a translational model of inflammatory pain. © 2014 The Authors European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  10. Semiarid watershed response in central New Mexico and its sensitivity to climate variability and change

    Directory of Open Access Journals (Sweden)

    E. R. Vivoni

    2009-06-01

    Full Text Available Hydrologic processes in the semiarid regions of the Southwest United States are considered to be highly susceptible to variations in temperature and precipitation characteristics due to the effects of climate change. Relatively little is known about the potential impacts of climate change on the basin hydrologic response, namely streamflow, evapotranspiration and recharge, in the region. In this study, we present the development and application of a continuous, semi-distributed watershed model for climate change studies in semiarid basins of the Southwest US. Our objective is to capture hydrologic processes in large watersheds, while accounting for the spatial and temporal variations of climate forcing and basin properties in a simple fashion. We apply the model to the Río Salado basin in central New Mexico since it exhibits both a winter and summer precipitation regime and has a historical streamflow record for model testing purposes. Subsequently, we use a sequence of climate change scenarios that capture observed trends for winter and summer precipitation, as well as their interaction with higher temperatures, to perform long-term ensemble simulations of the basin response. Results of the modeling exercise indicate that precipitation uncertainty is amplified in the hydrologic response, in particular for processes that depend on a soil saturation threshold. We obtained substantially different hydrologic sensitivities for winter and summer precipitation ensembles, indicating a greater sensitivity to more intense summer storms as compared to more frequent winter events. In addition, the impact of changes in precipitation characteristics overwhelmed the effects of increased temperature in the study basin. Nevertheless, combined trends in precipitation and temperature yield a more sensitive hydrologic response throughout the year.

  11. Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ-Induced IL-27 and Airway Hyperresponsiveness in Mice.

    Science.gov (United States)

    Liao, Wupeng; Tan, W S Daniel; Wong, W S Fred

    2016-06-01

    LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-γ-induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes/macrophages, and BALB/c mice were treated with LPS/IFN-γ, in the presence and absence of dexamethasone and/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS/IFN-γ-induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS/IFN-γ-induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS/IFN-γ markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS/IFN-γ also decreased total HDAC activity but increased the total histone acetyltransferase/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase/HDAC activity ratio in mouse lungs exposed to LPS/IFN-γ, possibly via suppression of PI3K/Akt/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2-related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders

  12. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: ESI (Environmental Sensitivity Index Shoreline Types - Lines and Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector lines and polygons representing the shoreline and coastal habitats of Central California classified according to the Environmental...

  13. Lengthened Cutaneous Silent Period in Fibromyalgia Suggesting Central Sensitization as a Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Seol-Hee Baek

    Full Text Available The pathogenesis of fibromyalgia (FM has not been clearly elucidated, but central sensitization, which plays an important role in the development of neuropathic pain, is considered to be the main mechanism. The cutaneous silent period (CSP, which is a spinal reflex mediated by A-delta cutaneous afferents, is useful for the evaluation of sensorimotor integration at the spinal and supraspinal levels. To understand the pathophysiology of FM, we compared CSP patterns between patients with FM and normal healthy subjects. Twenty-four patients with FM diagnosed in accordance with the 1990 American College of Rheumatology classification system and 24 age- and sex-matched healthy volunteers were recruited. The CSP was measured from the abductor pollicis brevis muscle. Demographic data, number of tender points, and visual analog scale and FM impact questionnaire scores were collected. The measured CSP and clinical parameters of the patient and control groups were compared. In addition, possible correlations between the CSP parameters and the other clinical characteristics were analyzed. Mean CSP latencies did not differ between patients (55.50 ± 10.97 ms and healthy controls (60.23 ± 11.87 ms; p = 0.158, although the mean CSP duration was significantly longer in patients (73.75 ± 15.67 ms than in controls (63.50 ± 14.05 ms; p = 0.021. CSP variables did not correlate with any clinical variables. The significantly longer CSP duration in FM patients suggests central dysregulation at the spinal and supraspinal levels, rather than peripheral small fiber dysfunction.

  14. Lengthened Cutaneous Silent Period in Fibromyalgia Suggesting Central Sensitization as a Pathogenesis.

    Science.gov (United States)

    Baek, Seol-Hee; Seok, Hung Youl; Koo, Yong Seo; Kim, Byung-Jo

    2016-01-01

    The pathogenesis of fibromyalgia (FM) has not been clearly elucidated, but central sensitization, which plays an important role in the development of neuropathic pain, is considered to be the main mechanism. The cutaneous silent period (CSP), which is a spinal reflex mediated by A-delta cutaneous afferents, is useful for the evaluation of sensorimotor integration at the spinal and supraspinal levels. To understand the pathophysiology of FM, we compared CSP patterns between patients with FM and normal healthy subjects. Twenty-four patients with FM diagnosed in accordance with the 1990 American College of Rheumatology classification system and 24 age- and sex-matched healthy volunteers were recruited. The CSP was measured from the abductor pollicis brevis muscle. Demographic data, number of tender points, and visual analog scale and FM impact questionnaire scores were collected. The measured CSP and clinical parameters of the patient and control groups were compared. In addition, possible correlations between the CSP parameters and the other clinical characteristics were analyzed. Mean CSP latencies did not differ between patients (55.50 ± 10.97 ms) and healthy controls (60.23 ± 11.87 ms; p = 0.158), although the mean CSP duration was significantly longer in patients (73.75 ± 15.67 ms) than in controls (63.50 ± 14.05 ms; p = 0.021). CSP variables did not correlate with any clinical variables. The significantly longer CSP duration in FM patients suggests central dysregulation at the spinal and supraspinal levels, rather than peripheral small fiber dysfunction.

  15. Minocycline attenuates mechanical allodynia and central sensitization following peripheral second-degree burn injury.

    Science.gov (United States)

    Chang, Yu-Wen; Waxman, Stephen G

    2010-11-01

    Burn injury induces severe pain that can be refractory to existing pharmacotherapies. The underlying mechanism of burn pain remains unclear. We previously established an animal model and reported that unilateral burn injury induces chronic and bilateral mechanical allodynia, which is associated with central sensitization and microglial activation in the spinal cord dorsal horn. Modulation of the activity of microglia and p38 mitogen-activated protein kinase (MAPK) has been shown to ameliorate neuropathic pain in several nerve-injury pain models. In the present study, we show in this rat model that daily treatment with the microglial inhibitor minocycline (10 mg/kg), administered at the time of burn injury and for 7 days thereafter, significantly attenuates ipsilateral and contralateral allodynia as assessed up to 1 month following burn injury. These sensory changes are paralleled by significant suppression of evoked hyperexcitability of dorsal-horn neurons and of the expression of phosphorylated p38 (phospho-p38) in OX42+ microglial cells within the dorsal horn. Our results suggest that modulation of inflammation at early times after burn injury may have long-lasting effects, attenuating central neuropathic mechanisms which contribute to pain after burn injury. We demonstrate, in a rodent model of burn-associated pain, that the microglial inhibitor minocycline, delivered at the time of burn injury and for 1 week thereafter, has long-lasting effects, attenuating microglial activation and neuronal hyperresponsiveness in the dorsal horns, and ameliorating allodynia for at least 1 month. Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors.

    Science.gov (United States)

    Itoh, K; Chiang, C-Y; Li, Z; Lee, J-C; Dostrovsky, J O; Sessle, B J

    2011-09-29

    Central sensitization is a crucial process underlying the increased neuronal excitability of nociceptive pathways following peripheral tissue injury and inflammation. Our previous findings have suggested that extracellular adenosine 5'-triphosphate (ATP) molecules acting at purinergic receptors located on presynaptic terminals (e.g., P2X2/3, P2X3 subunits) and glial cells are involved in the glutamatergic-dependent central sensitization induced in medullary dorsal horn (MDH) nociceptive neurons by application to the tooth pulp of the inflammatory irritant mustard oil (MO). Since growing evidence indicates that activation of P2X7 receptors located on glia is involved in chronic inflammatory and neuropathic pain, the aim of the present study was to test in vivo for P2X7 receptor involvement in this acute inflammatory pain model. Experiments were carried out in anesthetized Sprague-Dawley male rats. Single unit recordings were made in MDH functionally identified nociceptive neurons for which mechanoreceptive field, mechanical activation threshold and responses to noxious stimuli were tested. We found that continuous intrathecal (i.t.) superfusion over MDH of the potent P2X7 receptor antagonists brilliant blue G and periodated oxidized ATP could each significantly attenuate the MO-induced MDH central sensitization. MDH central sensitization could also be produced by i.t. superfusion of ATP and even more effectively by the P2X7 receptor agonist benzoylbenzoyl ATP. Superfusion of the microglial blocker minocycline abolished the MO-induced MDH central sensitization, consistent with reports that dorsal horn P2X7 receptors are mostly expressed on microglia. In control experiments, superfusion over MDH of vehicle did not produce any significant changes. These novel findings suggest that activation of P2X7 receptors in vivo may be involved in the development of central sensitization in an acute inflammatory pain model. Copyright © 2011 IBRO. All rights reserved.

  17. A Multi-sensor Approach to Identify Crop Sensitivity Related to Climate Variability in Central India

    Science.gov (United States)

    Mondal, P.; DeFries, R. S.; Jain, M.; Robertson, A. W.; Galford, G. L.; Small, C.

    2012-12-01

    Agriculture is a primary source of livelihood for over 70% of India's population, with staple crops (e.g. winter wheat) playing a pivotal role in satisfying an ever-increasing food-demand of a growing population. Agricultural yield in India has been reported to be highly correlated with the timing and total amount of monsoon rainfall and/or temperature depending on crop type. With expected change in future climate (temperature and precipitation), significant fluctuations in crop yields are projected for near future. To date, little work has identified the sensitivity of cropping intensity, or the number of crops planted in a given year, to climate variability. The objective of this study is to shed light on relative importance of different climate parameters through a statistical analysis of inter-annual variations in cropping intensity at a regional scale, which may help identify adaptive strategies in response to future climate anomalies. Our study focuses on a highly human-modified landscape in central India, and uses a multi-sensor approach to determine the sensitivity of agriculture to climate variability. First, we assembled the 16-day time-series of 250m Moderate Resolution Imaging Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI), and applied a spline function-based smoothing algorithm to develop maps of monsoon and winter crops in Central India for a decadal time-span. A hierarchical model involving moderate resolution Landsat (30m) data was used to estimate the heterogeneity of the spectral signature within the MODIS dataset (250m). We then compared the season-specific cropping patterns with spatio-temporal variability in climate parameters derived from the Tropical Rainfall Measuring Mission (TRMM) data. Initial data indicates that the existence of a monsoon crop has moderate to strong correlation with wet season end date (ρ = .522), wet season length (ρ = .522), and the number of rainy days during wet season (ρ = .829). Existence of a winter

  18. Central nociceptive sensitization vs. spinal cord training: Opposing forms of plasticity that dictate function after complete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Adam R Ferguson

    2012-10-01

    Full Text Available The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training. Conversely intradermal formalin impaired future spinal learning (24 h post-injection. Because the NMDA receptor has been implicated in formalin-induced central sensitization, we tested whether pretreatment with NMDA affects spinal learning. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24h. These data provide strong evidence for an

  19. Central nociceptive sensitization vs. spinal cord training: opposing forms of plasticity that dictate function after complete spinal cord injury

    OpenAIRE

    Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Grau, James W.

    2012-01-01

    The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive) stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI) field in...

  20. Sensitivity and specificity of multispectral imaging in detecting central serous chorioretinopathy.

    Science.gov (United States)

    Zhu, Xuemei; Cheng, Yong; Pan, Xue; Jin, Enzhong; Li, Shanshan; Zhao, Mingwei; Li, Xiaoxin

    2017-07-01

    Central serous chorioretinopathy (CSCR) is a common and idiopathic retinal disorder that affects young to middle aged adults. The aim of this study was to describe the characteristics of eyes with CSCR using a light-emitting diode (LED)-based multispectral imaging (MSI) system and to evaluate the diagnostic reliability of MSI compared to fluorescein angiography (FA) in detecting CSCR. A total of 56 eyes among 52 patients with 1 or more retinal pigment epithelium (RPE) abnormality were retrospectively enrolled in the study. The patients underwent complete examination, including optical coherence tomography, FA, indocyanine-green angiography, and MSI. MSI images were retrospectively reviewed by experienced masked graders. Diagnoses that were made based on MSI alone were compared with those that were made using FA. Sensitivity and specificity were calculated, and the morphological features on MSI were summarized. Among 56 eyes in 52 patients, MSI detected 22 of 26 true-positive CSCR cases but missed 4 FA-confirmed lesions. Further, it correctly excluded 30 of 30 non-CSCR lesions. The sensitivity and specificity of MSI were 84.6 and 100%, respectively, for identifying CSCR. Using MSI, RPE leakage was observed in 25 (96.2%) of 26 eyes with CSCR, which was comparable to the performance of FA. Dome-shaped areas of signal, which corresponded to fluid accumulation associated with neurosensory retinal detachment or RPE detachment were observed in 23 (88.5%) of 26 eyes. As a non-invasive technique, MSI permitted the visualization of RPE leakage and neurosensory detachment and allowed good detection of CSCR in this selected clinical population. Lasers Surg. Med. 49:498-505, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Expanded Distribution of Pain as a Sign of Central Sensitization in Individuals With Symptomatic Knee Osteoarthritis.

    Science.gov (United States)

    Lluch Girbés, Enrique; Dueñas, Lirios; Barbero, Marco; Falla, Deborah; Baert, Isabel A C; Meeus, Mira; Sánchez-Frutos, José; Aguilella, Luis; Nijs, Jo

    2016-08-01

    Expanded distribution of pain is considered a sign of central sensitization (CS). The relationship between recording of symptoms and CS in people with knee osteoarthritis (OA) has been poorly investigated. The aim of this study was to examine whether the area of pain assessed using pain drawings relates to CS and clinical symptoms in people with knee OA. This was a cross-sectional study. Fifty-three people with knee OA scheduled to undergo primary total knee arthroplasty were studied. All participants completed pain drawings using a novel digital device, completed self-administration questionnaires, and were assessed by quantitative sensory testing. Pain frequency maps were generated separately for women and men. Spearman correlation coefficients were computed to reveal possible correlations between the area of pain and quantitative sensory testing and clinical symptoms. Pain frequency maps revealed enlarged areas of pain, especially in women. Enlarged areas of pain were associated with higher knee pain severity (rs=.325, PCentral Sensitization Inventory (rs=.456, P<.01). No significant associations were observed between the area of pain and the remaining clinical symptoms and measures of CS. Firm conclusions about the predictive role of pain drawings cannot be drawn. Further evaluation of the reliability and validity of pain area extracted from pain drawings in people with knee OA is needed. Expanded distribution of pain was correlated with some measures of CS in individuals with knee OA. Pain drawings may constitute an easy way for the early identification of CS in people with knee OA, but further research is needed. © 2016 American Physical Therapy Association.

  2. Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats

    Directory of Open Access Journals (Sweden)

    Jinseok Yeo

    2017-01-01

    Full Text Available Background. The chronic postischemia pain (CPIP model is an animal model using ischemia/reperfusion injury that mimics the symptoms of complex regional pain syndrome type I. Glutathione (GSH prevents ischemia/reperfusion injury by scavenging free radicals. We conducted this study to investigate the protective effect of GSH in CPIP rats via changes of mechanical allodynia and phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. Methods. We divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200 mg/kg, and CPIP + GSH 500 mg/kg. Rats in the sham and CPIP groups received normal saline and rats in the other groups received GSH at the designated doses thirty minutes prior to reperfusion. Withdrawal thresholds were evaluated before sugery as well as 1, 3, and 7 days after surgery. pGluN1 level in the spinal cord was also measured. Results. GSH treated rats show a significant increase in the withdrawal thresholds of both hind paws as compared with the CPIP group dose-dependently. The expression of pGluN1 in the GSH treated rats significantly decreased as compared to the CPIP group (all P < 0.05. Conclusion. These findings suggest that GSH inhibited the development of mechanical allodynia and central sensitization in CPIP rats.

  3. Central fuel banking to reduce the number of proliferation sensitive enrichment activities

    International Nuclear Information System (INIS)

    Cserhati, A.

    2008-01-01

    Central fuel banking is a complex international political, economic and technical concept that aims to reduce uncontrolled spreading of uranium enrichment technology in the world in order to prevent proliferation of nuclear weapons. This paper first gives an outline of the notions: 'non-proliferation', the 'front-end' of the fuel cycle, the scope of fuel baking, nuclear fuel and the 60 years of enrichment technology. Enrichment technology is highly concentrated in the nuclear weapon states and other developed countries, but this is not exclusive any more. The technology is spreading. The global demand for enrichment services - parallel to massive nuclear investments in the civil sector and the ageing of older facilities - is constantly growing. Proliferation sensitivity calls for an effective and comprehensive non-proliferation regime. The solution may be multilateralizing the nuclear fuel cycle. After a historical overview, the proposals on multilateral nuclear approaches are presented. The assessment of the proposals is complex in the dimensions of: the non-proliferation aim, the assurance of supply aspect and other variables such as legal issues and non-nuclear inducements. A general evaluation and the recommendations of the Expert Panel of the IAEA are introduced outlining a plan on a middle- and long-term basis. The conclusion of the paper stresses the importance and challenge in finding the 'new balance' between obligations and interests of the members of the global community stating that the answers will have a significant impact on the nuclear indus- try, world wide economics and security policy. (orig.)

  4. Sensitivity analysis of ozone formation and transport for a central California air pollution episode.

    Science.gov (United States)

    Jin, Ling; Tonse, Shaheen; Cohan, Daniel S; Mao, Xiaoling; Harley, Robert A; Brown, Nancy J

    2008-05-15

    We developed a first- and second-order sensitivity analysis approach with the decoupled direct method to examine spatial and temporal variations of ozone-limiting reagents and the importance of local vs upwind emission sources in the San Joaquin Valley of central California for a 5 day ozone episode (Jul 29th to Aug 3rd, 2000). Despite considerable spatial variations, nitrogen oxides (NO(x)) emission reductions are overall more effective than volatile organic compound (VOC) control for attaining the 8 h ozone standard in this region for this episode, in contrast to the VOC control that works better for attaining the prior 1 h ozone standard. Interbasin source contributions of NO(x) emissions are limited to the northern part of the SJV, while anthropogenic VOC (AVOC) emissions, especially those emitted at night, influence ozone formation in the SJV further downwind. Among model input parameters studied here, uncertainties in emissions of NO(x) and AVOC, and the rate coefficient of the OH + NO2 termination reaction, have the greatest effect on first-order ozone responses to changes in NO(x) emissions. Uncertainties in biogenic VOC emissions only have a modest effect because they are generally not collocated with anthropogenic sources in this region.

  5. Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats.

    Science.gov (United States)

    Yeo, Jinseok; Jung, Hoon; Lee, Hyerim

    2017-01-01

    The chronic postischemia pain (CPIP) model is an animal model using ischemia/reperfusion injury that mimics the symptoms of complex regional pain syndrome type I. Glutathione (GSH) prevents ischemia/reperfusion injury by scavenging free radicals. We conducted this study to investigate the protective effect of GSH in CPIP rats via changes of mechanical allodynia and phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. We divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200 mg/kg, and CPIP + GSH 500 mg/kg. Rats in the sham and CPIP groups received normal saline and rats in the other groups received GSH at the designated doses thirty minutes prior to reperfusion. Withdrawal thresholds were evaluated before sugery as well as 1, 3, and 7 days after surgery. pGluN1 level in the spinal cord was also measured. GSH treated rats show a significant increase in the withdrawal thresholds of both hind paws as compared with the CPIP group dose-dependently. The expression of pGluN1 in the GSH treated rats significantly decreased as compared to the CPIP group (all P central sensitization in CPIP rats.

  6. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury

    OpenAIRE

    Carlton, Susan M.; Du, Junhui; Tan, Huai Yu; Nesic, Olivera; Hargett, Gregory L.; Bopp, Anne C.; Yamani, Ammar; Lin, Qing; Willis, William D.; Hulsebosch, Claire E.

    2009-01-01

    Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of ab...

  7. The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Villegas-Pineda, Julio César, E-mail: jcvillegas@cinvestav.mx; Toledo-Leyva, Alfredo, E-mail: toledo_leyva@hotmail.com; Osorio-Trujillo, Juan Carlos, E-mail: clostrujillo2@yahoo.com.mx; Hernández-Ramírez, Verónica Ivonne, E-mail: arturomvi@hotmail.com; Talamás-Rohana, Patricia, E-mail: ptr@cinvestav.mx

    2017-02-15

    Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and β3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.

  8. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    Science.gov (United States)

    Burston, James J; Sagar, Devi Rani; Shao, Pin; Bai, Mingfeng; King, Emma; Brailsford, Louis; Turner, Jenna M; Hathway, Gareth J; Bennett, Andrew J; Walsh, David A; Kendall, David A; Lichtman, Aron; Chapman, Victoria

    2013-01-01

    Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA

  9. Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint.

    Directory of Open Access Journals (Sweden)

    James J Burston

    Full Text Available Osteoarthritis (OA of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2 receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation

  10. Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.

    Science.gov (United States)

    Wei, Jia-You; Liu, Cui-Cui; Ouyang, Han-Dong; Ma, Chao; Xie, Man-Xiu; Liu, Meng; Lei, Wan-Long; Ding, Huan-Huan; Wu, Shao-Ling; Xin, Wen-Jun

    2017-10-01

    Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats. Spinal local application of methylglyoxal also induced mechanical allodynia and central sensitization in normal rats. Moreover, administration of bortezomib upregulated the expression of receptors for advanced glycation end products (RAGE) and phosphorylated STAT3 (p-STAT3) in dorsal horn. Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment. In addition, inhibition of STAT3 activity by S3I-201 attenuated bortezomib-induced mechanical allodynia and central sensitization. Local knockdown of STAT3 also ameliorated the mechanical allodynia induced by bortezomib administration. Our results suggest that accumulation of methylglyoxal may activate the RAGE/STAT3 signaling pathway in dorsal horn, and contributes to the spinal central sensitization and persistent pain induced by bortezomib treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients.

    Science.gov (United States)

    White, Hillary D; Robinson, Thomas D

    2015-08-01

    Fibromyalgia is a diffuse chronic pain condition that occurs predominantly in women and may be under-reported in men. Symptoms include a loss of feeling of well-being and generalized widespread flu-like muscle aches and pain that fail to resolve due to central sensitization of nociceptive neurons. It has commonalities with a myriad of other chronic pain conditions which include PTSD, "Gulf War Syndrome", and various stress-induced conditions caused, for example, by viral infection, emotional or physical stress, trauma, combat, accident or surgery. It is not understood why some individuals are susceptible to this condition and others are not. White et al., elsewhere in this issue, present a clinical feasibility study designed to test the hypothesis that 1) low or deficient testosterone serum levels are linked to a high risk for an inflamed nociceptive nervous system and resultant chronic pain states, and 2) a testosterone transdermal gel applied once a day by fibromyalgia patients can be an effective therapeutic against chronic pain. Here, a short profile of fibromyalgia is provided along with a brief summary of best practices currently recommended by clinical specialists. The link between testosterone and pain is then discussed, with an overview of scientific studies that lay the foundation for testosterone as a possible important additional therapeutic that has the potential to be safely administered and effective but also avoid the adverse effects of other therapeutics. Finally, novel mechanisms by which testosterone therapy is likely to down-modulate pain signaling are proposed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. An Evaluation of Central Sensitization in Patients With Sickle Cell Disease.

    Science.gov (United States)

    Campbell, Claudia M; Moscou-Jackson, Gyasi; Carroll, C Patrick; Kiley, Kasey; Haywood, Carlton; Lanzkron, Sophie; Hand, Matthew; Edwards, Robert R; Haythornthwaite, Jennifer A

    2016-05-01

    Central sensitization (CS), nociceptive hyperexcitability known to amplify and maintain clinical pain, has been identified as a leading culprit responsible for maintaining pain in several chronic pain conditions. Recent evidence suggests that it may explain differences in the symptom experience of individuals with sickle cell disease (SCD). Quantitative sensory testing (QST) can be used to examine CS and identify individuals who may have a heightened CS profile. The present study categorized patients with SCD on the basis of QST responses into a high or low CS phenotype and compared these groups according to measures of clinical pain, vaso-occlusive crises, psychosocial factors, and sleep continuity. Eighty-three adult patients with SCD completed QST, questionnaires, and daily sleep and pain diaries over a 3-month period, weekly phone calls for 3 months, and monthly phone calls for 12 months. Patients were divided into CS groups (ie, no/low CS [n = 17] vs high CS [n = 21]), on the basis of thermal and mechanical temporal summation and aftersensations, which were norm-referenced to 47 healthy control subjects. High CS subjects reported more clinical pain, vaso-occlusive crises, catastrophizing, and negative mood, and poorer sleep continuity (Ps < .05) over the 18-month follow-up period. Future analyses should investigate whether psychosocial disturbances and sleep mediate the relationship between CS and pain outcomes. In general, SCD patients with greater CS had more clinical pain, more crises, worse sleep, and more psychosocial disturbances compared with the low CS group. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Segmental hyperalgesia to mechanical stimulus in interstitial cystitis/bladder pain syndrome: evidence of central sensitization.

    Science.gov (United States)

    Lai, H Henry; Gardner, Vivien; Ness, Timothy J; Gereau, Robert W

    2014-05-01

    We investigate if subjects with interstitial cystitis/bladder pain syndrome demonstrate mechanical or thermal hyperalgesia, and whether the hyperalgesia is segmental or generalized (global). Ten female subjects with interstitial cystitis/bladder pain syndrome and 10 age matched female controls without comorbid fibromyalgia or narcotic use were recruited for quantitative sensory testing. Using the method of limits, pressure pain and heat pain thresholds were measured. Using the method of fixed stimulus, the visual analog scale pain experienced was recorded when a fixed pressure/temperature was applied. The visual analog scale pain rated by female subjects with interstitial cystitis/bladder pain syndrome was significantly higher than that rated by female control subjects when a fixed mechanical pressure (2 or 4 kg) was applied to the suprapubic (T11) area (p = 0.028). There was an up shift of the stimulus-response curve, which corresponded to the presence of mechanical hyperalgesia in the suprapubic area in interstitial cystitis/bladder pain syndrome. However, the visual analog scale pain rated by subjects with interstitial cystitis/bladder pain syndrome was not different from that rated by controls when a fixed pressure was applied at the other body sites (T1 arm, L4 leg, S2-3 sacral). No difference in visual analog scale pain rating was noted when a fixed heat stimulus (35C or 37C) was applied to any of the body sites tested (T1, T11, L4, S2). There was no difference in pressure pain thresholds or thermal pain thresholds between subjects with interstitial cystitis/bladder pain syndrome and controls. Female subjects with interstitial cystitis/bladder pain syndrome showed segmental hyperalgesia to mechanical pressure stimulation in the suprapubic area (T10-T12). This segmental hyperalgesia may be explained in part by spinal central sensitization. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  14. Pain experiences of patients with musculoskeletal pain + central sensitization: A comparative Group Delphi Study.

    Science.gov (United States)

    Schäfer, Axel Georg Meender; Joos, Leonie Johanna; Roggemann, Katharina; Waldvogel-Röcker, Kerstin; Pfingsten, Michael; Petzke, Frank

    2017-01-01

    Central sensitization (CS) is regarded as an important contributing factor for chronification of musculoskeletal pain (MSP). It is crucial to identify CS, as targeted multimodal treatment may be indicated. The primary objective of this study was therefore to explore pain experience of individuals with MSP+CS in order to gain a better understanding of symptoms in relation to CS from a patient perspective. The secondary objective was to investigate whether pain experiences of patients with MSP+CS differ from those of individuals with neuropathic pain (NP). We conducted a comparative Group Delphi Study including patients with MSP+CS and neuropathic pain (NP). 13 guiding questions were used to gather information about sensory discriminatory, affective and associated bodily, mental and emotional phenomena related to the pain experience of patients. Descriptions were categorized using qualitative content analysis. Additionally, patients completed several pain related questionnaires. Nine participants with MSP+CS and nine participants with NP participated. The Delphi procedure revealed three main themes: psycho-emotional factors, bodily factors and environmental factors. Descriptions of patients with MSP+CS showed a complex picture, psycho-emotional factors seem to have a considerable impact on pain provocation, aggravation and relief. Impairments associated with mental ability and psyche affected many aspects of daily life. In contrast, descriptions of patients with NP revealed a rather mechanistic and bodily oriented pain experience. Patients with MSP+CS reported distinct features in relation to their pain that were not captured with current questionnaires. Insight in patient's pain experience may help to choose and develop appropriate diagnostic instruments.

  15. Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain.

    Science.gov (United States)

    Starkweather, Angela R; Heineman, Amy; Storey, Shannon; Rubia, Gil; Lyon, Debra E; Greenspan, Joel; Dorsey, Susan G

    2016-02-01

    Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Uplifting of the Jiamusi Block in the eastern Central Asian Orogenic Belt, NE China: evidence from basin provenance and geochronology

    Science.gov (United States)

    Liu, Yongjiang; Wen, Quanbo; Han, Guoqing; Li, Wei

    2010-05-01

    The main part of Jiamusi Block, named as Huanan-Uplift, is located in the northeastern Heilongjiang, China. The Huanan-Uplift is surrounded by many relatively small Mesozoic-Cenozoic basins, e.g. Sanjiang Basin, Hulin Basin, Boli Basin, Jixi Basin, Shuangyashan Basin and Shuanghua Basin. However previous research works were mainly focused on stratigraphy and palaeontology of the basins, therefore, the coupling relation between the uplift and the surrounding basins have not been clear. Based on the field investigations, conglomerate provenance studies of the Houshigou Formation in Boli Basin, geochronology of the Huanan-Uplift basement, we have been studied the relationships between Huanan-Uplift and the surrounding basins. The regional stratigraphic correlations indicates that the isolated basins in the area experienced the same evolution during the period of the Chengzihe and the Muling Formations (the Early Cretaceous). The paleogeography reconstructions suggest that the area had been a large-scale basin as a whole during the Early Cretaceous. The Huanan-Uplift did not exist. The paleocurrent directions, sandstone and conglomerate provenance analyses show that the Huanan-Uplift started to be the source area of the surrounding basins during the period of Houshigou Formation (early Late Cretaceous), therefore, it suggests that the Jiamusi Block commenced uplift in the early Late Cretaceous. The granitic gneisses in Huanan-Uplift give 494-415 Ma monazite U-Th-total Pb ages, 262-259 Ma biotite and 246-241 Ma K-feldspar 40Ar/39Ar ages. The cooling rates of 1-2 ℃/Ma from 500-260 Ma and 10-11 ℃/Ma from 260-240 Ma have been calculated based on the ages. This suggests that the Jiamusi Block had a rapid exhumation during late Permian, which should be related to the closure of the Paleo-Asian Ocean between the Siberian and North China continents. It is concluded that during the late Paleozoic the Jiamusi Block was stable with a very slow uplifting. With the closure of

  17. Layer-by-Layer Formation of Block-Copolymer-Derived TiO2 for Solid-State Dye-Sensitized Solar Cells

    KAUST Repository

    Guldin, Stefan

    2011-12-15

    Morphology control on the 10 nm length scale in mesoporous TiO 2 films is crucial for the manufacture of high-performance dye-sensitized solar cells. While the combination of block-copolymer self-assembly with sol-gel chemistry yields good results for very thin films, the shrinkage during the film manufacture typically prevents the build-up of sufficiently thick layers to enable optimum solar cell operation. Here, a study on the temporal evolution of block-copolymer-directed mesoporous TiO 2 films during annealing and calcination is presented. The in-situ investigation of the shrinkage process enables the establishment of a simple and fast protocol for the fabrication of thicker films. When used as photoanodes in solid-state dye-sensitized solar cells, the mesoporous networks exhibit significantly enhanced transport and collection rates compared to the state-of-the-art nanoparticle-based devices. As a consequence of the increased film thickness, power conversion efficiencies above 4% are reached. Fabrication of sufficiently thick mesoporous TiO 2 photoelectrodes with morphology control on the 10 nm length scale is essential for solid-state dye-sensitized solar cells (ss-DSC). This study of the temporal evolution of block-copolymer-directed mesoporous TiO 2 films during annealing and calcination enables the build-up of sufficiently thick films for high-performance ssDSC devices. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. NEW FINDINGS OF PERMIAN MARINE AND TERRESTRIAL FOSSILS IN CENTRAL IRAN (THE KALMARD BLOCK AND THEIR SIGNIFICANCE FOR CORRELATION OF THE TETHYAN, URALIAN, AND WEST EUROPEAN SCALES

    Directory of Open Access Journals (Sweden)

    ERNST JA. LEVEN

    2011-11-01

    Full Text Available The Permian litho- and biostratigraphy of the Darin and Gachal sections of the southern part of the Kalmard block, Central Iran, are described. Like the Permian in the Halvan Mountain sections of the northern part of the block, the southern sections include four formations, namely the Chili, Chah-Kular, Hermez, and Rizi. The Chah-Kular Formation, which is first established in the present paper, corresponds to the Sartakht Formation of the northern sections. Its lowest beds contain plant fossils characteristic of the Lower Permian of Europe and partly, China. The Chili Formation includes fusulinids of the Kalaktashian assemblage, which has been dated as Sakmarian based on conodonts. Fusulinids in the Halvan Mt. section, which appear at the top of the formation, were previously found in conglomerate pebbles at the base of the overlying Sartakht Formation. As the beds with the Halvan Mt. fusulinid assemblage occur above beds with late Sakmarian conodonts, the assemblage may be of Artinskian age. However, that assemblage includes taxa usually not present either in the Artinskian fusulinid assemblage of the Urals or in the fusulinids of the Yakhtashian Stage that succeeds the Sakmarian in the Tethyan scale. A new fusulinid species (Nonpseudofusulina darinensis Leven, sp. nov. and plants Annularia carinata Gutbier, Pecopteris monyi Zeiller P. cyathea (Schlotheim Brongniart, Fascipteris cf. robusta (Kawasaki Broutin, Discinites sp., Taeniopteris cf. crassicaulis Jongmans & Gothan are described. Palaeogeography of Central Iran region and adjacent areas is discussed. 

  19. Detecting Zones of High Rock Uplift Rates Using Topographic Analysis and OSL Signals: A Case of Study in The Jalisco Block (Central Mexico)

    Science.gov (United States)

    Castillo, M.; Ferrari, L.; Munoz-Salinas, E.; Cruz-Zaragoza, E.

    2013-12-01

    The topography of mountainous settings records information of the interaction among tectonics, climate and erosion. Rivers respond to rapid tectonic uplift rates by increasing their incision rate and propagating knickpoints. River incision also enhances the local relief that can be quantified at broad spatial scales studying river basins. We evaluate the response of rivers to different tectonic uplift rates by analyzing the river basins and stream profiles of the Jalisco block (Central Mexico). The Jalisco Block is a complex tectonic unit bounded to the northwest and the northeast by the Puerto Vallarta graben and the Amatlán de Cañas half graben, respectively, and controlled to the southwest by the subduction of the Rivera Plate beneath the North America Plate. We analyze the means of local relief, normalized channel steepness index (ksn), ridgeline convexity and bottom-valley concavity of river basins, ranging from ~13 to ~2300 km 2 of drainage area as well as slope-area plots, to detect zones of high rock uplift and river incision. We complement our topographic analysis using OSL signals from sandy sediment samples extracted from riverbed to estimate the erosion rates operating on the landscape. Our results indicate that river incision is higher in the north and northwestern sector of the Jalisco Block, regardless that there valleys are filled with Plio-Quaternary lava flows. Rivers draining in the western sector of the Jalisco Block appear to have reached a quasi-steady state where OSL signals and ksn values exhibit a scaling with basins elevation.

  20. Central Sensitization Inventory as a Predictor of Worse Quality of Life Measures and Increased Length of Stay Following Spinal Fusion.

    Science.gov (United States)

    Bennett, E Emily; Walsh, Kevin M; Thompson, Nicolas R; Krishnaney, Ajit A

    2017-08-01

    Central sensitization is abnormal and intense enhancement of pain mechanism by the central nervous system. Patients with central sensitization may be at higher risk of poor outcomes after spinal fusion. The Central Sensitivity Inventory (CSI) was developed to identify and quantify key symptoms related to central sensitization. In 664 patients who underwent thoracic and/or lumbar fusion, we evaluated retrospectively pretreatment CSI as a predictor of postoperative quality of life measures, length of stay, and discharge status. Preoperative Pain Disability Questionnaire scores, Patient Health Questionnaire-9 scores, and EuroQol-5 Dimensions index scores were significantly worse in patients with preoperative CSI ≥40 compared with patients with preoperative CSI <40 (P < 0.0001 for all). After adjusting for demographic variables, operation duration, and preoperative health status, preoperative CSI was significantly associated with higher postoperative Pain Disability Questionnaire total score (unadjusted P < 0.001, adjusted P = 0.009), higher postoperative Patient Health Questionnaire-9 score (unadjusted P < 0.001, adjusted P = 0.001), and lower postoperative EuroQol-5 Dimensions index (unadjusted P < 0.001, adjusted P = 0.001). For each 10-unit increase in CSI, average length of stay increased by 6.4% (95% confidence interval 0.4%-12.6%, P = 0.035). The odds of being discharged home after adjusting for confounders was not statistically related to preoperative CSI (P = 0.0709). Preoperative CSI was associated with worse quality of life outcomes and increased length of stay after spinal fusions. CSI may be an additional measure in evaluating patients preoperatively to better predict successful spinal fusion outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

    Directory of Open Access Journals (Sweden)

    Fang Li

    2006-03-01

    Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in

  2. Central nociceptive sensitization vs. spinal cord training: opposing forms of plasticity that dictate function after complete spinal cord injury.

    Science.gov (United States)

    Ferguson, Adam R; Huie, J Russell; Crown, Eric D; Grau, James W

    2012-01-01

    The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive) stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI) field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome) learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training). Conversely intradermal formalin impaired future spinal learning (24 h post-injection). Because formalin-induced central sensitization has been shown to involve NMDA receptor activation, we tested whether pre-treatment with NMDA would also affect spinal learning in manner similar to formalin. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24 h. These

  3. Preparation of pH-sensitive amphiphilic block star polymers, their self-assembling characteristics and release behavior on encapsulated molecules

    KAUST Repository

    Song, Xiaowan

    2016-05-28

    Poly(ethylene glycol) (PEG), a polymer with excellent biocompatibility, was widely used to form nanoparticles for drug delivery applications. In this paper, based on PEG, a series of pH-sensitive amphiphilic block star polymers of poly(ethylene glycol)-block-poly(ethoxy ethyl glycidyl ether) (PEG-b-PEEGE) with different hydrophobic length were synthesized by living anionic ring-opening polymerization method. The products were characterized using 1H NMR and gel permeation chromatography. These copolymers could self-assemble in aqueous solution to form micellar structure with controlled morphologies. Transmission electron microscopy showed that the nanoparticles are spherical or rodlike with different hydrophilic mass fractions. The pH response of polymeric aggregates from PEG-b-PEEGE was detected by fluorescence probe technique at different pH. A pH-dependent release behavior was observed and pH-responsiveness of PEG-b-PEEGE was affected by the hydrophobic block length. These results demonstrated that star-shaped polymers (PEG-b-PEEGE) are attractive candidates as anticancer drug delivery carriers. © 2016 Springer-Verlag Berlin Heidelberg

  4. The influence of anatase-rutile mixed phase and ZnO blocking layer on dye-sensitized solar cells based on TiO2nanofiberphotoanodes

    Science.gov (United States)

    Ding, Jianning; Li, Yan; Hu, Hongwei; Bai, Li; Zhang, Shuai; Yuan, Ningyi

    2013-01-01

    High performance is expected in dye-sensitized solar cells (DSSCs) that utilize one-dimensional (1-D) TiO2 nanostructures owing to the effective electron transport. However, due to the low dye adsorption, mainly because of their smooth surfaces, 1-D TiO2 DSSCs show relatively lower efficiencies than nanoparticle-based ones. Herein, we demonstrate a very simple approach using thick TiO2 electrospun nanofiber films as photoanodes to obtain high conversion efficiency. To improve the performance of the DSCCs, anatase-rutile mixed-phase TiO2 nanofibers are achieved by increasing sintering temperature above 500°C, and very thin ZnO films are deposited by atomic layer deposition (ALD) method as blocking layers. With approximately 40-μm-thick mixed-phase (approximately 15.6 wt.% rutile) TiO2 nanofiber as photoanode and 15-nm-thick compact ZnO film as a blocking layer in DSSC, the photoelectric conversion efficiency and short-circuit current are measured as 8.01% and 17.3 mA cm-2, respectively. Intensity-modulated photocurrent spectroscopy and intensity-modulated photovoltage spectroscopy measurements reveal that extremely large electron diffusion length is the key point to support the usage of thick TiO2 nanofibers as photoanodes with very thin ZnO blocking layers to obtain high photocurrents and high conversion efficiencies.

  5. Impaired sensitivity to beta 2 integrin-blocking in ICAM-1-mediated neutrophil migration in ulcerative colitis

    DEFF Research Database (Denmark)

    Vainer, B; Brimnes, J; Claesson, M H

    2001-01-01

    BACKGROUND: Factors influencing the directed migration of neutrophils into colonic tissue in ulcerative colitis (UC) are poorly described. ICAM-1 has recently been shown to possess chemotactic properties, and the aim of this study was to evaluate the involvement of beta 2 integrins in this ICAM-1......-mediated migration. METHODS: The chemotactic effect of ICAM-1 on neutrophils isolated from 13 UC patients and 17 healthy volunteers was studied in microchemotaxis chambers. Physiological concentrations of ICAM-1 (0.05-500 pM) were separated from neutrophils by nitrocellulose filters, and cell migration...... was evaluated using the leading front technique. beta 2 integrins on neutrophils were blocked with antibodies to CD11a, CD11b, CD11c and CD18, and migration towards ICAM-1 was examined. RESULTS: Migration towards ICAM-1 was equal for UC and control neutrophils, showing a bell-shaped ICAM-1 dosemigratory...

  6. Epicutaneous immunotherapy (EPIT blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

    Directory of Open Access Journals (Sweden)

    Lucie Mondoulet

    Full Text Available Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT on these processes.Mice were sensitized by gavages with whole peanut protein extract (PPE given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure.Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2 and reduced villus/crypt ratios (1.6±0.15. In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (50 eosinophils/mm(2, p<0.05, mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05, IL-5 (p<0.05, and IL-13 (p<0.05--GATA-3 (p<0.05, and intestinal villus sub-atrophia (2.3±0.15. EPIT also increased specific IgG2a (p<0.05 and mRNA expression of Foxp3 (p<0.05 in the esophageal mucosa.Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

  7. Hydroxylated xestospongins block inositol-1,4,5-trisphosphate-induced Ca2+ release and sensitize Ca2+-induced Ca2+ release mediated by ryanodine receptors.

    Science.gov (United States)

    Ta, Tram Anh; Feng, Wei; Molinski, Tadeusz F; Pessah, Isaac N

    2006-02-01

    Inositol-1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) often coexist within the endoplasmic/sarcoplasmic reticulum (ER/SR) membrane and coordinate precise spatial and temporal coding of Ca(2+) signals in most animal cells. Xestospongin C (XeC) was shown to selectively block IP(3)-induced Ca(2+) release and IP(3)R-mediated signaling (Gafni et al., 1997). We have further studied the specificity of xestospongin structures possessing ring hydroxyl (-OH) substituents toward IP(3)R, RyR, and ER/SR Ca(2+)-ATPase (SERCA) activities. XeC potently inhibits IP(3)R, weakly inhibits RyR1, and lacks activity toward SERCA1 and SERCA2. XeD (9-OH XeC), 7-OH-XeA, and araguspongin C isolated from the marine sponge Xestospongia species also inhibit IP(3)-mediated Ca(2+) release and lack activity toward SERCA. However, these hydroxylated derivatives possess a unique activity in that they enhance Ca(2+)-induced Ca(2+) release from SR vesicles by a mechanism involving the sensitization of RyR1 channels within the same concentration range needed to block IP(3)-induced Ca(2+) release. These results show that xestospongins and related structures lack direct SERCA inhibitory activity, as suggested by some previous studies. A new finding is that XeD and related structures possessing a hydroxylated oxaquinolizidine ring are IP(3)R blockers that also enhance Ca(2+)-induced Ca(2+) release mediated by RyRs. In intact cells, the actions of XeD are blocked by ryanodine pretreatment and do not interfere with thapsigargin-mediated Ca(2+) mobilization stemming from SERCA block. Hydroxylated bis-oxaquinolizadine derivatives isolated from Xestospongia species are novel bifunctional reagents that may be useful in ascertaining how IP(3)Rs and RyRs contribute to cell signaling.

  8. Neoproterozoic diamictite-bearing sedimentary rocks in the northern Yili Block and their constraints on the Precambrian evolution of microcontinents in the Western Central Asian Orogenic Belt

    Science.gov (United States)

    He, Jingwen; Zhu, Wenbin; Zheng, Bihai; Wu, Hailin; Cui, Xiang; Lu, Yuanzhi

    2015-12-01

    The origin and tectonic setting of Precambrian sequences in the Central Asian Orogenic Belt (CAOB) have been debated due to a lack of high resolution geochronological data. Answering this question is essential for the understanding of the tectonic framework and Precambrian evolution of the blocks within the CAOB. Here we reported LA-ICP-MS detrital zircon U-Pb ages and in-situ Hf isotopic data for Neoproterozoic sedimentary cover in the northern Yili Block, an important component of the CAOB, in order to provide information on possible provenance and regional tectonic evolution. A total of 271 concordant U-Pb zircon ages from Neoproterozoic sedimentary cover in the northern Yili Block define three major age populations of 1900-1400 Ma, 1300-1150 Ma and 700-580 Ma, which are quite different from cratons and microcontinents involved in the CAOB. Although it is not completely consistent with the local basement ages, an autochthonous provenance interpretation is more suitable. Some zircon grains show significant old Hf model ages (TDMC; 3.9-2.4 Ga) and reveal continental crust as old as Paleoarchean probably existed. Continuous Mesoproterozoic zircon age populations exhibit large variations in the εHf(t) ratios, suggesting the long-time involvement of both reworked ancient crust and juvenile material. Similar Mesoproterozoic evolution pattern is identified in many continental terranes involved in the CAOB that surround the Tarim Craton. Based on our analysis and published research, we postulate that the northern Yili Block, together with Chinese Central Tianshan, Kyrgyz North Tianshan and some other microcontinents surrounding the Tarim Craton, once constituted the continental margin of the Tarim Craton in the Mesoproterozoic, formed by long-lived accretionary processes. Most of the late Neoproterozoic zircons exhibit significant positive εHf(t) ratios, suggesting the addition of juvenile crust. It is consistent with the tectonic event related to the East Africa

  9. Balancing "hands-on" with "hands-off" physical therapy interventions for the treatment of central sensitization pain in osteoarthritis.

    Science.gov (United States)

    Lluch Girbés, E; Meeus, M; Baert, I; Nijs, J

    2015-04-01

    Traditional understanding of osteoarthritis-related pain has recently been challenged in light of evidence supporting a key role of central sensitization in a subgroup of this population. This fact may erroneously lead musculoskeletal therapists to conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied exclusively. The aim of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are also addressed. Future studies should explore the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes against current approaches for chronic osteoarthritis-related pain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model.

    Science.gov (United States)

    Ryu, Tae Ha; Jung, Kyung Young; Ha, Mi Jin; Kwak, Kyung Hwa; Lim, Dong Gun; Hong, Jung Gil

    2010-03-01

    Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

  11. Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor

    OpenAIRE

    Tricarico, Domenico; Barbieri, Mariagrazia; Camerino, Diana Conte

    2000-01-01

    Taurine is a sulphonic aminoacid present in high amounts in various tissues including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and anti-schaemic effects. The cellular mechanism of action of taurine is under investigation and appears to involve the interaction of the sulphonic aminoacid with several ion channels.Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K+ channel (KATP) ...

  12. Ore Reserve Estimation of Saprolite Nickel Using Inverse Distance Method in PIT Block 3A Banggai Area Central Sulawesi

    Science.gov (United States)

    Khaidir Noor, Muhammad

    2018-03-01

    Reserve estimation is one of important work in evaluating a mining project. It is estimation of the quality and quantity of the presence of minerals have economic value. Reserve calculation method plays an important role in determining the efficiency in commercial exploration of a deposit. This study was intended to calculate ore reserves contained in the study area especially Pit Block 3A. Nickel ore reserve was estimated by using detailed exploration data, processing by using Surpac 6.2 by Inverse Distance Weight: Squared Power estimation method. Ore estimation result obtained from 30 drilling data was 76453.5 ton of Saprolite with density of 1.5 ton/m3 and COG (Cut Off Grade) Ni ≥ 1.6 %, while overburden data was 112,570.8 tons with waste rock density of 1.2 ton/m3 . Striping Ratio (SR) was 1.47 : 1 smaller than Stripping Ratio ( SR ) were set of 1.60 : 1.

  13. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: ALERTS (Vulnerable Resource Location Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector points representing locations in Central California that should be highlighted for protection due to the presence of certain highly...

  14. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: SOCECON (Socioeconomic Resource Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains socioeconomic resource data for the following types of locations in Central California: access, airport, aquaculture, beach, boat ramp, USCG...

  15. Insulin sensitivity and lipid profiles in girls with central precocious puberty before and during gonadal suppression

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Mouritsen, Annette; Mogensen, Signe Sloth

    2010-01-01

    Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis.......Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis....

  16. SENSITIVE EFFECTS OF POTASSIUM AND CALCIUM CHANNEL BLOCKING AND ATP-SENSITIVE POTASSIUM CHANNEL ACTIVATORS ON SEMINAL VESICLE SMOOTH MUSCLE CONTRACTIONS

    Directory of Open Access Journals (Sweden)

    H SADRAEI

    2000-12-01

    Full Text Available Background. Seminal vesicle smooth muscle contraction is mediated through sympathetic and parasympathetic neurons activity. Although seminal vesicle plays an important role in male fertility, but little attention is given to mechanism involved in contraction of this organ.
    Methods. In this study effects of drugs which activate ATP - sensitive K channels and blockers of K and Ca channels were examined on contraction of guinea - pig isolated seminal vesicle due to electrical filled stimulation (EFS, noradrenaline, carbachol and KCI.
    Results. The K channel blocker tetraethyl ammonium potentate the EFS responses at all frequencies, while, the ATP - sensitive K channel inhibitor glibenclamide and the K channel opener levcromakalim, diazoxide, minoxidil and Ca channel blocker nifedipine all had relaxant effect on guinea - pig seminal vesicle.
    Discussion. This study indicate that activities of K and Ca channels is important in regulation of seminal vesicle contraction due to nerve stimulation, noradrenaline or carbachol.

  17. Robustness analysis of complex networks with power decentralization strategy via flow-sensitive centrality against cascading failures

    Science.gov (United States)

    Guo, Wenzhang; Wang, Hao; Wu, Zhengping

    2018-03-01

    Most existing cascading failure mitigation strategy of power grids based on complex network ignores the impact of electrical characteristics on dynamic performance. In this paper, the robustness of the power grid under a power decentralization strategy is analysed through cascading failure simulation based on AC flow theory. The flow-sensitive (FS) centrality is introduced by integrating topological features and electrical properties to help determine the siting of the generation nodes. The simulation results of the IEEE-bus systems show that the flow-sensitive centrality method is a more stable and accurate approach and can enhance the robustness of the network remarkably. Through the study of the optimal flow-sensitive centrality selection for different networks, we find that the robustness of the network with obvious small-world effect depends more on contribution of the generation nodes detected by community structure, otherwise, contribution of the generation nodes with important influence on power flow is more critical. In addition, community structure plays a significant role in balancing the power flow distribution and further slowing the propagation of failures. These results are useful in power grid planning and cascading failure prevention.

  18. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

    Science.gov (United States)

    Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

    2017-08-01

    The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

  19. Venom of the Chilean Latrodectus mactans alters bovine spermatozoa calcium and function by blocking the TEA-sensitive K(+) current.

    Science.gov (United States)

    Navarrete, Patricia; Martínez-Torres, Ataúlfo; Gutiérrez, Raúl Sánchez; Mejía, Fernando Romero; Parodi, Jorge

    2010-08-01

    The morphology and size of spermatozoa make it difficult to study the functional properties of the plasma membrane, however, some studies have revealed the presence of a number of ion channels in this cell. We measured the calcium (Ca(++)) influx induced by depolarization of the plasma membrane and by venom isolated from the Chilean black widow spider (Latrodectus mactans), and functional changes in the presence of either high potassium or total venom. Our results indicate that the venom increased the Ca(++) influx, with an EC50 of 6.1 microg/mL and triggering the acrosome reaction in 43.26% of the cells. The application of potassium (10 mM K(+)) or total venom (10 microg/mL) did not affect the morphology or DNA stability of the sperm. The effects induced by high K(+) and venom suggest that direct blocking of K(+) currents alters the passive properties of the plasma membrane, leading to the entry of Ca(++). These results show the importance of functional changes induced by depolarizing the spermatozoa and by venom. This venom possesses one or more molecules that may be used as pharmacological tools for studies on spermatozoa and have potential applications in reproductive biotechnology.

  20. Microinjection of naltrexone into the central, but not the basolateral, amygdala blocks the anxiolytic effects of diazepam in the plus maze

    Science.gov (United States)

    Burghardt, Paul R.; Wilson, Marlene A.

    2009-01-01

    The amygdala is involved in behavioral and physiological responses to fear, and the anxiolytic properties of several drugs are localized to this region. Activation of endogenous opioid systems is known to occur in response to stress and a growing body of literature suggests that opioid systems regulate the properties of anxiolytic drugs. These experiments sought to elucidate the role of opioid receptors in the central (CeA) and basolateral (BLA) nuclei of the amygdala in regulating the anxiolytic properties of ethanol and diazepam. Male rats fitted with cannula received bilateral microinjections of the non-selective opioid receptor antagonist naltrexone (NAL) immediately followed by systemic delivery of either ethanol (1 g/kg) or diazepam (2 mg/kg) in the elevated plus maze. Both diazepam and ethanol decreased anxiety-like behavior. Delivery of NAL into the CeA blocked the anxiolytic properties of diazepam. Delivery of NAL into the BLA slightly increased open arm avoidance, but had no effect on the anxiolytic properties of diazepam. Microinjection of NAL into either nucleus failed to block the effects of ethanol. These results were specific to the anxiolytic properties of diazepam, since baseline behaviors were unaffected by microinjection of naltrexone. Microinjection of lidocaine produced results distinct from NAL and failed to block the anxiolytic actions of diazepam. These studies indicate distinct roles for opioid receptor systems in the CeA and BLA in regulating the anxiolytic properties of diazepam in the elevated plus maze. Further, opioid receptor systems in the CeA and BLA do not regulate the anxiolytic properties of ethanol in this test. PMID:16123750

  1. Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation

    Directory of Open Access Journals (Sweden)

    Freeman Michael D

    2009-04-01

    Full Text Available Abstract Objective it has been established that chronic neck pain following whiplash is associated with the phenomenon of central sensitization, in which injured and uninjured parts of the body exhibit lowered pain thresholds due to an alteration in central pain processing. it has furthermore been hypothesized that peripheral sources of nociception in the muscles may perpetuate central sensitization in chronic whiplash. the hypothesis explored in the present study was whether myofascial trigger points serve as a modulator of central sensitization in subjects with chronic neck pain. Design controlled case series. Setting outpatient chronic pain clinic. Subjects seventeen patients with chronic and intractable neck pain and 10 healthy controls without complaints of neck pain. Intervention symptomatic subjects received anesthetic infiltration of myofascial trigger points in the upper trapezius muscles and controls received the anesthetic in the thigh. Outcome measures: pre and post injection cervical range of motion, pressure pain thresholds (ppt over the infraspinatus, wrist extensor, and tibialis anterior muscles. sensitivity to light (photophobia and subjects' perception of pain using a visual analog scale (vas were also evaluated before and after injections. only the ppt was evaluated in the asymptomatic controls. Results immediate (within 1 minute alterations in cervical range of motion and pressure pain thresholds were observed following an average of 3.8 injections with 1–2 cc of 1% lidocaine into carefully identified trigger points. cervical range of motion increased by an average of 49% (p = 0.000 in flexion and 44% (p = 0.001 in extension, 47% (p = 0.000 and 28% (p Conclusion the present data suggest that myofascial trigger points serve to perpetuate lowered pain thresholds in uninjured tissues. additionally, it appears that lowered pain thresholds associated with central sensitization can be immediately reversed, even when associated

  2. Ytterbium oxide nanodots via block copolymer self-assembly and their efficacy to dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kwang-Won; Ahn, Sungwoo; Lim, Sung-Hwan; Jin, Ming Hao; Song, Jeemin; Yun, Seung-Young [Department of Chemistry, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 156-756 (Korea, Republic of); Kim, Hyeon Mo; Kim, Gi Jeong [Sooyang Chemtec Co., Ltd., Digital-ro 32-gil, Guro-gu, Seoul 152-777 (Korea, Republic of); Ok, Kang Min [Department of Chemistry, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 156-756 (Korea, Republic of); Hong, Jongin, E-mail: hongj@cau.ac.kr [Department of Chemistry, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 156-756 (Korea, Republic of)

    2016-02-28

    Graphical abstract: - Highlights: • A novel phosphor, Yb{sub 2}O{sub 3}, was developed as a UV-absorbing spectral converter for dye-sensitized solar cells (DSSCs). • The ordered Yb{sub 2}O{sub 3} nanodots trap more light and prevent charge recombination at the interfaces. • Their multifunctionality improves DSSC performance for both Ru-based and organic dyes. - Abstract: In this study, we develop a novel phosphor, Yb{sub 2}O{sub 3}, to be used as the spectral converter in dye-sensitized solar cells (DSSCs) for the efficient capture of ultraviolet light via down-conversion. These zero-dimensional nanodots with a high refractive index also allow more light to be trapped and can prevent charge recombination at the interfaces in the DSSCs. Compared to DSSCs without the nanodots, the DSSCs fabricated with the Yb{sub 2}O{sub 3} nanodots exhibits higher power-conversion efficiencies for both the N719 (10.5%) and CSD-01 (20.5%) dyes. The multifunctionality of the Yb{sub 2}O{sub 3} nanodots provides a new route for improving the performance of DSSCs.

  3. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: INDEX (Index Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains vector polygons representing the boundaries of all hardcopy cartographic products produced as part of the Environmental Sensitivity Index...

  4. ESI-PR16, Central La Plata, Puerto Rico 2000 (Environmental Sensitivity Index Map)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Environmental Sensitivity Index (ESI) maps are an integral component in oil-spill contingency planning and assessment. They serve as a source of information in the...

  5. Sensitivity of Coastal Environments and Wildlife to Spilled Oil: Central California: BIRDS (Bird Polygons)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for alcids, diving birds, gulls, terns, passerine birds, pelagic birds, raptors, shorebirds, wading birds,...

  6. Blocking anaplerotic entry of glutamine into the TCA cycle sensitizes K-Ras mutant cancer cells to cytotoxic drugs.

    Science.gov (United States)

    Saqcena, M; Mukhopadhyay, S; Hosny, C; Alhamed, A; Chatterjee, A; Foster, D A

    2015-05-14

    Cancer cells undergo a metabolic transformation that allows for increased anabolic demands, wherein glycolytic and tricarboxylic acid (TCA) cycle intermediates are shunted away for the synthesis of biological molecules required for cell growth and division. One of the key shunts is the exit of citrate from the mitochondria and the TCA cycle for the generation of cytosolic acetyl-coenzyme A that can be used for fatty acid and cholesterol biosynthesis. With the loss of mitochondrial citrate, cancer cells rely on the 'conditionally essential' amino acid glutamine (Q) as an anaplerotic carbon source for TCA cycle intermediates. Although Q deprivation causes G1 cell cycle arrest in non-transformed cells, its impact on the cancer cell cycle is not well characterized. We report here a correlation between bypass of the Q-dependent G1 checkpoint and cancer cells harboring K-Ras mutations. Instead of arresting in G1 in response to Q-deprivation, K-Ras-driven cancer cells arrest in either S- or G2/M-phase. Inhibition of K-Ras effector pathways was able to revert cells to G1 arrest upon Q deprivation. Blocking anaplerotic utilization of Q mimicked Q deprivation--causing S- and G2/M-phase arrest in K-Ras mutant cancer cells. Significantly, Q deprivation or suppression of anaplerotic Q utilization created synthetic lethality to the cell cycle phase-specific cytotoxic drugs, capecitabine and paclitaxel. These data suggest that disabling of the G1 Q checkpoint could represent a novel vulnerability of cancer cells harboring K-Ras and possibly other mutations that disable the Q-dependent checkpoint.

  7. Central sensitization in the trigeminal nucleus caudalis produced by a conjugate of substance P and the A subunit of cholera toxin.

    Science.gov (United States)

    Caudle, Robert M; King, Christopher; Nolan, Todd A; Suckow, Shelby K; Vierck, Charles J; Neubert, John K

    2010-09-01

    Individuals with chronic craniofacial pain experience symptoms that are consistent with central sensitization. In fact, central sensitization may constitute the major disease process in these conditions, particularly if the original injury has healed or the condition is idiopathic. To understand central sensitization we have developed a conjugate of substance P and cholera toxin (SP-CTA). SP-CTA is selectively taken up by cells that express neurokinin receptors. Twenty-four hours following intracisternal administration of SP-CTA, wild-type rats and mice demonstrated signs of persistent background nociception, but when tested for facial cold sensitivity, they did not differ from controls. However, treating the SP-CTA-injected animals with naloxone exposed cold hypersensitivity in the face. Mu-opioid receptor knockout mice treated with SP-CTA demonstrated hypersensitivity without naloxone treatment. These findings suggest that central sensitization leads to activation of an endogenous opioid system. The data also demonstrate that the intracisternal administration of SP-CTA in rodents is a useful model for studying central sensitization as a disease process without having to induce a peripheral injury. Central sensitization is a concern in many craniofacial pain conditions. In this project, we utilize a conjugate of substance P and the catalytic subunit of cholera toxin to induce central sensitization in the nucleus caudalis of rodents. The data indicate that the injected animals become hypersensitive in the face. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

  8. Studies on a novel multi-sensitive hydrogel: influence of the biomimetic phosphorylcholine end-groups on the PEO-PPO-PEO tri-block co-polymers.

    Science.gov (United States)

    Meng, Sheng; Guo, Zhang; Wang, Qiong; Liu, ZongJun; Wang, QiHong; Zhong, Wei; Du, QiangGuo

    2011-01-01

    In the present study, a biomimetic phosphorylcholine group was employed in the end-capping modification of PEO-PPO-PEO tri-block co-polymers (Pluronic(®)). The structures of the resulting materials were characterized by (1)H-NMR and GPC. The effects of the additional phosphorylcholine end-groups to the thermo-sensitive sol-gel transition behaviors of the aqueous solutions of the resulting polymers were studied by rheology test in neutral (0.1 M NaCl) aqueous solutions and in acidic solutions (pH 3). It was found that the phosphorylcholine-end-capped Pluronic hydrogels still kept their thermo-sensitive mechanical properties with a slight change on the sol-gel transition behaviors. The phosphorylcholine-modified Pluronics exhibited a response to the change of the pH value, which made this kind of material a multi-sensitive hydrogel system. Also, the resulting polymers showed improved hemocompatibilities in the blood coagulation test using full human blood.

  9. N-ethylmaleimide-sensitive fusion protein (NSF) is involved in central sensitization in the spinal cord through GluR2 subunit composition switch after inflammation.

    Science.gov (United States)

    Katano, Tayo; Furue, Hidemasa; Okuda-Ashitaka, Emiko; Tagaya, Mitsuo; Watanabe, Masahiko; Yoshimura, Megumu; Ito, Seiji

    2008-06-01

    Central sensitization, similar to long-term potentiation in the hippocampus, refers to the increased synaptic efficacy established in somatosensory neurons in the dorsal horn of the spinal cord following tissue injury or nerve damage. In the course of inflammation, many proteins including glutamate receptors are assumed to be dynamically reorganized in the postsynaptic density (PSD) and involved in persistent pain. Mechanical hyperalgesia induced by intraplantar injection of complete Freund's adjuvant (CFA) was inhibited at 4 h, but not at 24 h, by indomethacin, an inhibitor of prostanoid synthesis. To elucidate the nature of the molecule(s) involved in the late phase of inflammatory pain, we analysed the PSD fraction prepared from the lumbar spinal cord of rats before and 24 h after CFA injection by conducting two-dimensional differential gel electrophoresis. N-ethylmaleimide-sensitive fusion protein (NSF) was identified as a downregulated protein in the PSD by MALDI-TOF MS and immunoblotting. Concomitant with the decrease in NSF, GluR2 and GluR3 were decreased and GluR1 was conversely increased in the PSD fraction 24 h after CFA injection. In vivo patch-clamp recordings of rats 24 h after CFA injection showed that excitatory postsynaptic currents of dorsal horn neurons evoked by pinch stimuli to inflamed skin were inwardly rectified and inhibited by 60% by philanthotoxin-433, a selective inhibitor of the Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These results suggest that peripheral inflammation gives rise to central sensitization in the spinal cord through subunit composition switch of AMPA receptors in the late phase.

  10. Altered central sensitization and pain modulation in the CNS in chronic joint pain

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Skou, Søren Thorgaard; Nielsen, Thomas Arendt

    2015-01-01

    and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety...

  11. Sedimentary environments and stratigraphy of the carbonate-silicilastic deposits of the Shirgesht Formation: implications for eustasy and local tectonism in the Kalmard Block, Central Iran

    Directory of Open Access Journals (Sweden)

    aram bayetgoll

    2015-10-01

    Full Text Available Introduction   Sedimentological and sequence stratigraphic analysis providing insight into the main relationships between sequence architecture and stacking pattern, syn/post-depositional tectonics, and eustatic sea-level fluctuations (Gawthorpe and Leeder 2000; Zecchin et al. 2003, 2004; Carpentier et al. 2007. Relative variations in sea level are due to tectonic activity and eustasy. The Shirgesht Formation in the Kalmard Block of Central Iran provides a useful case study for to determine the processes responsible on internal architecture and stacking pattern of depositional sequences in a half-graben basin. In the Shirgesht Formation, siliciclastic and carbonate successions of the Kalmard Basin, the cyclic stratigraphic record is the result of the complex interaction of regional uplift, eustasy, local tectonics, sediment supply, and sedimentary processes (Bayet-Goll 2009, 2014; Hosseini-Barzi and Bayet-Goll 2009.     Material & Methods   Lower Paleozoic successions in Tabas and Kalmard blocks from Central Iran share the faunal and floral characteristics with other Gondwana sectors such as south-western Europe and north Africa–Middle East (Ghaderi et al. 2009. The geology of these areas was outlined by Ruttner et al. (1968 and by Bruton et al. (2004. The Cambrian-Middle Triassic strata in the Kalmard Block were deposited in a shallow water platform that possesses lithologic dissimilarities with the Tabas area (Aghanabati 2004. The occurrence of two active faults indicates clearly that Kalmard basin formed a mobile zone throughout the Paleozoic so that lithostratigraphic units show considerably contrasting facies in comparison with Tabas basin (Hosseini-Barzi and Bayet-Goll 2009; Bayet-Goll 2014 . The Shirgesht Formation in the Block Kalmard is mainly composed of carbonate-siliciclastic successions that disconformability overlain Kalmard Formation (attributed to Pre-Cambrian and is underlain by Gachal (Carboniferous or Rahdar (Devonian

  12. Sedimentary environments and stratigraphy of the carbonate-silicilastic deposits of the Shirgesht Formation: implications for eustasy and local tectonism in the Kalmard Block, Central Iran

    Directory of Open Access Journals (Sweden)

    reza Mousavi-Harami

    2015-09-01

    Full Text Available   Introduction   Sedimentological and sequence stratigraphic analysis providing insight into the main relationships between sequence architecture and stacking pattern, syn/post-depositional tectonics, and eustatic sea-level fluctuations (Gawthorpe and Leeder 2000 Zecchin et al. 2003, 2004 Carpentier et al. 2007. Relative variations in sea level are due to tectonic activity and eustasy. The Shirgesht Formation in the Kalmard Block of Central Iran provides a useful case study for to determine the processes responsible on internal architecture and stacking pattern of depositional sequences in a half-graben basin. In the Shirgesht Formation, siliciclastic and carbonate successions of the Kalmard Basin, the cyclic stratigraphic record is the result of the complex interaction of regional uplift, eustasy, local tectonics, sediment supply, and sedimentary processes (Bayet-Goll 2009, 2014 Hosseini-Barzi and Bayet-Goll 2009.     Material & Methods   Lower Paleozoic successions in Tabas and Kalmard blocks from Central Iran share the faunal and floral characteristics with other Gondwana sectors such as south-western Europe and north Africa–Middle East (Ghaderi et al. 2009. The geology of these areas was outlined by Ruttner et al. (1968 and by Bruton et al. (2004. The Cambrian-Middle Triassic strata in the Kalmard Block were deposited in a shallow water platform that possesses lithologic dissimilarities with the Tabas area (Aghanabati 2004. The occurrence of two active faults indicates clearly that Kalmard basin formed a mobile zone throughout the Paleozoic so that lithostratigraphic units show considerably contrasting facies in comparison with Tabas basin (Hosseini-Barzi and Bayet-Goll 2009 Bayet-Goll 2014 . The Shirgesht Formation in the Block Kalmard is mainly composed of carbonate-siliciclastic successions that disconformability overlain Kalmard Formation (attributed to Pre-Cambrian and is underlain by Gachal (Carboniferous or

  13. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta

    DEFF Research Database (Denmark)

    Nansen, A; Randrup Thomsen, A

    2001-01-01

    LPS is the major active agent in the pathogenesis of Gram-negative septic shock. In this report we have studied the influence of concurrent viral infection on the outcome of LPS-induced shock. We find that infection with vesicular stomatitis virus sensitizes mice to LPS at an early time point......-depleted and gene-targeted mice. Our results revealed that while NK cell depletion and elimination of IFN-gamma partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-alphabetaR-deficient mice. Thus...... hyperproduction of TNF-alpha was completely abrogated in IFN-alphabetaR-deficient mice, indicating that the principal mechanism underlying rapid virus-induced sensitization to LPS is an IFN-alphabeta-mediated priming of mice for an augmented production of TNF-alpha in response to LPS. This conclusion was further...

  14. Activation of central angiotensin type 2 receptors by compound 21 improves arterial baroreflex sensitivity in rats with heart failure.

    Science.gov (United States)

    Gao, Juan; Zucker, Irving H; Gao, Lie

    2014-10-01

    In a previous study we demonstrated that central administration of compound 21 (C21), a nonpeptide AT2R agonist, inhibited sympathetic tone in normal rats. In this study, we hypothesized that C21 exerts a similar effect in rats with coronary ligation-induced heart failure (HF). C21 was intracerebroventricularly infused for 7 days by osmotic mini pump. Blood pressure (BP) and heart rate (HR) were recorded by radiotelemetry in the conscious state to measure spontaneous arterial baroreflex sensitivity. Urine was collected for measurement of norepinephrine excretion. On the last day of C21 treatment, renal sympathetic nerve activity, BP, and HR were directly recorded under anesthesia, and the induced arterial baroreflex sensitivity was evaluated. Protein expressions of neuronal nitric oxide synthase (nNOS) and angiotensin II type 1 receptor (AT1R) in the subfornical organ, paraventricular nucleus, rostral ventrolateral medulla, and nucleus tractus solitarius were determined by Western blot analysis. C21-treated HF rats displayed significantly less norepinephrine excretion (2,385.6 ± 121.1 vs. 3,677.3 ± 147.6 ng/24 hours; P baroreflex sensitivity and induced arterial baroreflex sensitivity. Bolus intracerebroventricular injection of angiotensin II-evoked pressor and sympatho-excitatory responses were attenuated in the C21-treated HF rats, which displayed upregulated nNOS and downregulated AT1R expression in the subfornical organ, paraventricular nucleus, and rostral ventrolateral medulla. Activation of central angiotensin II type 2 receptor AT2R by C21 suppresses sympathetic outflow in rats with HF by improving baroreflex sensitivity and may provide important benefit in the HF syndrome. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity.

    Science.gov (United States)

    Sun, Shuhong; Wang, Ran; Song, Jianwen; Guan, Ming; Li, Na; Zhang, Xiaotian; Zhao, Zhenwen; Zhang, Junjie

    2017-11-01

    Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine. Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Upregulation of ATX expression in obese patients and mice is closely related with insulin resistance and impaired glucose tolerance. However, the mechanism of ATX expression in adipocytes remains largely unknown. In this study, we found that glycoprotein 130 (gp130)-mediated Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) activation was required for abundant ATX expression in adipocytes. Through gp130, the interleukin 6 (IL-6) family cytokines, such as IL-6, leukemia inhibitory factor, cardiotrophin-1, and ciliary neurotrophic factor, upregulated ATX expression in adipocytes. ATX contributes to the induction of insulin resistance and lipolysis in IL-6-stimulated adipocytes. Oral administration of gp130 inhibitor SC144 suppressed ATX expression in adipose tissue, decreased plasma ATX, LPA, and FFA levels, and significantly improved insulin sensitivity and glucose tolerance in high-fat diet-fed obese mice. In summary, our results indicate that the activation of gp130-JAK-STAT3 pathway by IL-6 family cytokines has an important role in regulating ATX expression in adipocytes and that gp130 is a promising target in the management of obesity-associated glucose metabolic diseases. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  16. Heat-sensitive lysis mutants of Bacillus subtilis 168 blocked at three different stages of peptidoglycan synthesis.

    Science.gov (United States)

    Buxton, R S; Ward, J B

    1980-10-01

    Three heat-sensitive mutants of Bacillus subtilis 168, which lysed at the non-permissive temperature, have been shown under these conditions to be defective in the synthesis of peptidoglycan. This was caused by lesions in three different stages of peptidoglycan synthesis.In one mutant (ddl), D-alanine: D-alanine ligase was defective, leading to the accumulation of UDP-MurAc-L-Ala-D-Glu-meso-A,pm ; the ddl mutation was closely linked(87 yo cotransducible) with dal, specifying alanine racemase. In a second mutant (dapE),the lesion was in N-acetyl-L-diaminopimelate deacylase, resulting in UDP-MurAc-L-Ala-D-Glu being accumulated, whilst in a third mutant (ptg-1435), UDP-MurAc-L-Ala-D-Glumeso-A,pm-D-Ala-D-Ala was the peptidoglycan precursor accumulated although the enzyme defect has not been ascertained. Both dapE and ptg-1435 were located between metC and pyr(AD), dapE being 25% cotransducible and ptg-1435 were located between metC and pyr(AD), dapE being 25% cotransducible with pyr(AD).

  17. Blocking NF-κB sensitizes non-small cell lung cancer cells to histone deacetylase inhibitor induced extrinsic apoptosis through generation of reactive oxygen species.

    Science.gov (United States)

    Karthik, Selvaraju; Sankar, Renu; Varunkumar, Krishnamoorthy; Anusha, Chidambaram; Ravikumar, Vilwanathan

    2015-02-01

    NF-κB signalling is one of the main cell survival pathways that attenuate the anticancer efficacy of therapeutic drugs. Previous studies demonstrated that the histone deacetylase (HDAC) inhibitor induces apoptosis in some malignancies through multiple mechanisms including up-regulation of death receptors, disruption of Hsp90 function and generation of reactive oxygen species (ROS). However, HDAC inhibitor also induces a cell survival signal through NF-κB activation. In this report, we found that romidepsin, a class I HDAC inhibitor, induces NF-κB activation in A549 non-small-cell lung cancer (NSCLC) cells. We also found that inhibition of A549 cells with bortezomib (proteasome inhibitor) has blocked IκB degradation that leads to the loss of NF-κB activation and translocation which enhanced the romidepsin induced mitochondrial injury and sensitizes NSCLC cells to apoptosis. Romidepsin significantly enhances NF-κB reporter gene transcription and these effects were inhibited by bortezomib as determined by reporter gene assay. Consistently, the combined exposure of romidepsin and bortezomib reversed the effects on IκB degradation as evident with IL-8, p50 and p65 (NF-κB) expression. Apoptosis was markedly sensitized with greater ROS generation and more cell death in A549 cell lines. These events are most closely related in that bortezomib prevents the romidepsin mediated RelA acetylation and NF-κB activation, resulting in caspase activation. A strategy of blocking NF-κB activation to enhance HDAC inhibitor activity warrants further attention in NSCLC cells. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Sensitivity of wetland hydrology to external climate forcing in central Florida

    NARCIS (Netherlands)

    Lammertsma, E.I.; Donders, T.H.; Pearce, C.; Cremer, H.; Gaiser, E.E.; Wagner-Cremer, F.

    2015-01-01

    Available proxy records from the Florida peninsula give a varying view on hydrological changes during the late Holocene. Here we evaluate the consistency and sensitivity of local wetland records in relation to hydrological changes over the past ~. 5. ka based on pollen and diatom proxies from peat

  19. Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor.

    Science.gov (United States)

    Tricarico, D; Barbieri, M; Camerino, D C

    2000-06-01

    Taurine is a sulphonic aminoacid present in high amounts in various tissues including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and anti-schaemic effects. The cellular mechanism of action of taurine is under investigation and appears to involve the interaction of the sulphonic aminoacid with several ion channels. Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K(+) channel (K(ATP)) immediately after excision and on channels that underwent rundown. The cytoplasmic application of 20 mM of taurine reduced the K(ATP) current; this effect was reverted by washout of the drug solution. In this experimental condition the IC(50) was 20.1 mM. After rundown, taurine inhibited the K(ATP) current with similar efficacy. Competition experiments showed that taurine shifted the dose-response inhibition curve of glybenclamide to the left on the log-dose axis without significantly affecting those of ATP or Ca(2+) ion. Single channel recording revealed that taurine affects the close state of the channel prolonging it and reducing the bursts duration. Our data indicate that taurine inhibits the muscular K(ATP) channel interfering with the glybenclamide site on the sulphonylurea receptor of the channel or on the site allosterically coupled to it. During ischaemia and hypoxia, the skeletal and heart muscles undergo several changes; for example, the activation of K(ATP) channels and loss of the intracellular taurine content. The depletion of taurine during ischaemia would contribute to the early activation of K(ATP) channels and salvage the intracellular ATP content.

  20. Stabilization of the Central Part of Tropomyosin Molecule Alters the Ca2+-sensitivity of Actin-Myosin Interaction.

    Science.gov (United States)

    Shchepkin, D V; Matyushenko, A M; Kopylova, G V; Artemova, N V; Bershitsky, S Y; Tsaturyan, A K; Levitsky, D I

    2013-07-01

    We show that the mutations D137L and G126R, which stabilize the central part of the tropomyosin (Tm) molecule, increase both the maximal sliding velocity of the regulated actin filaments in the in vitro motility assay at high Са(2+) concentrations and the Са(2+)-sensitivity of the actin-myosin interaction underlying this sliding. Based on an analysis of the recently published data on the structure of the actin-Tm-myosin complex, we suppose that the physiological effects of these mutations in Tm can be accounted for by their influence on the interactions between the central part of Tm and certain sites of the myosin head.

  1. Src-family kinases activation in spinal microglia contributes to central sensitization and chronic pain after lumbar disc herniation.

    Science.gov (United States)

    Huang, Yangliang; Li, Yongyong; Zhong, Xiongxiong; Hu, Yuming; Liu, Pan; Zhao, Yuanshu; Deng, Zhen; Liu, Xianguo; Liu, Shaoyu; Zhong, Yi

    2017-01-01

    Background Lumbar disc herniation is a major cause of radicular pain, but the underlying mechanisms remain largely unknown. Spinal activation of src-family kinases are involved in the development of chronic pain from nerve injury, inflammation, and cancer. In the present study, the role of src-family kinases activation in lumbar disc herniation-induced radicular pain was investigated. Results Lumbar disc herniation was induced by implantation of autologous nucleus pulposus, harvest from tail, in lumbar 4/5 spinal nerve roots of rat. Behavior test and electrophysiologic data showed that nucleus pulposus implantation induced persistent mechanical allodynia and thermal hyperalgesia and increased efficiency of synaptic transmission in spinal dorsal horn which underlies central sensitization of pain sensation. Western blotting and immunohistochemistry staining revealed that the expression of phosphorylated src-family kinases was upregulated mainly in spinal microglia of rats with nucleus pulposus. Intrathecal delivery of src-family kinases inhibitor PP2 alleviated pain behaviors, decreased efficiency of spinal synaptic transmission, and reduced phosphorylated src-family kinases expression. Furthermore, we found that the expression of ionized calcium-binding adapter molecule 1 (marker of microglia), tumor necrosis factor-α, interleukin 1 -β in spinal dorsal horn was increased in rats with nucleus pulposus. Therapeutic effect of PP2 may be related to its capacity in reducing the expression of these factors. Conclusions These findings suggested that central sensitization was involved in radicular pain from lumbar disc herniation; src-family kinases-mediated inflammatory response may be responsible for central sensitization and chronic pain after lumbar disc herniation.

  2. The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-02-01

    OBJECTIVES: Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (+\\/- leg) pain disorders. METHODS: This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (+\\/- leg) pain were assessed using a standardized assessment protocol. After each assessment, patients\\' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various clinical criteria. RESULTS: Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive\\/negative predictive values, positive\\/negative likelihood ratios). DISCUSSION: By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  3. RESTING SYMPATHETIC BAROREFLEX SENSITIVITY IN SUBJECTS WITH LOW AND HIGH TOLERANCE TO CENTRAL HYPOVOLEMIA INDUCED BY LOWER BODY NEGATIVE PRESSURE

    Directory of Open Access Journals (Sweden)

    Carmen eHinojosa-Laborde

    2014-06-01

    Full Text Available Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock. The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA and sympathetic baroreflex sensitivity (BRS are attenuated in male and female subjects who have low tolerance (LT to central hypovolemia induced by lower body negative pressure (LBNP. MSNA and diastolic arterial pressure (DAP were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms. LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28, and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats-1•mmHg-1, p=0.29. We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS.

  4. Stabilization of the Central Part of Tropomyosin Molecule Alters the Ca2+-sensitivity of Actin-Myosin Interaction

    OpenAIRE

    Shchepkin, D.V.; Matyushenko, A. M.; Kopylova, G. V.; Artemova, N. V.; Bershitsky, S. Y.; Tsaturyan, A. K.; Levitsky, D. I.

    2013-01-01

    We show that the mutations D137L and G126R, which stabilize the central part of the tropomyosin (Tm) molecule, increase both the maximal sliding velocity of the regulated actin filaments in the in vitro motility assay at high Са 2+ concentrations and the Са 2+-sensitivity of the actin-myosin interaction underlying this sliding. Based on an analysis of the recently published data on the structure of the actin–Tm–myosin complex, we suppose that the physiological effects of these mutations in Tm...

  5. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta

    DEFF Research Database (Denmark)

    Nansen, A; Randrup Thomsen, A

    2001-01-01

    LPS is the major active agent in the pathogenesis of Gram-negative septic shock. In this report we have studied the influence of concurrent viral infection on the outcome of LPS-induced shock. We find that infection with vesicular stomatitis virus sensitizes mice to LPS at an early time point...... following infection. Treatment of mice with the chemical IFN inducer, polyinosinic:polycytidylic acid, has a similar effect. This hypersensitivity to LPS correlated with hyperproduction of TNF-alpha in vivo. The cellular and molecular mechanisms underlying this phenomenon were investigated using Ab......-depleted and gene-targeted mice. Our results revealed that while NK cell depletion and elimination of IFN-gamma partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-alphabetaR-deficient mice. Thus...

  6. Identification of Subgroups of Women with Carpal Tunnel Syndrome with Central Sensitization.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Fernández-Muñoz, Juan J; Navarro-Pardo, Esperanza; da-Silva-Pocinho, Ricardo F; Ambite-Quesada, Silvia; Pareja, Juan A

    2016-09-01

    Identification of subjects with different sensitization mechanisms can help to identify better therapeutic strategies for carpal tunnel syndrome (CTS). The aim of the current study was to identify subgroups of women with CTS with different levels of sensitization. A total of 223 women with CTS were recruited. Self-reported variables included pain intensity, function, disability, and depression. Pressure pain thresholds (PPT) were assessed bilaterally over median, ulnar, and radial nerves, C5-C6 joint, carpal tunnel, and tibialis anterior to assess widespread pressure pain hyperalgesia. Heat (HPT) and cold (CPT) pain thresholds were also bilaterally assessed over the carpal tunnel and the thenar eminence to determine thermal pain hyperalgesia. Pinch grip force between the thumb and the remaining fingers was calculated to determine motor assessment. Subgroups were determined according to the status on a previous clinical prediction rule: PPT over the affected C5-C6 joint 66 points. The ANOVA showed that women within group 1 (positive rule, n = 60) exhibited bilateral widespread pressure hyperalgesia (P < 0.001) and bilateral thermal thresholds (P < 0.001) than those within group 2 (negative rule, n = 162). Women in group 1 also exhibited higher depression than those in group 2 (P = 0.023). No differences in self-reported variables were observed. This study showed that a clinical prediction rule originally developed for identifying women with CTS who are likely to respond favorably to manual physical therapy was able to identify women exhibiting higher widespread pressure hyper-sensitivity and thermal hyperalgesia. This subgroup of women with CTS exhibiting higher sensitization may need specific therapeutic programs. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Sensitivity of boundary layer variables to PBL schemes over the central Tibetan Plateau

    Science.gov (United States)

    Xu, L.; Liu, H.; Wang, L.; Du, Q.; Liu, Y.

    2017-12-01

    Planetary Boundary Layer (PBL) parameterization schemes play critical role in numerical weather prediction and research. They describe physical processes associated with the momentum, heat and humidity exchange between land surface and atmosphere. In this study, two non-local (YSU and ACM2) and two local (MYJ and BouLac) planetary boundary layer parameterization schemes in the Weather Research and Forecasting (WRF) model have been tested over the central Tibetan Plateau regarding of their capability to model boundary layer parameters relevant for surface energy exchange. The model performance has been evaluated against measurements from the Third Tibetan Plateau atmospheric scientific experiment (TIPEX-III). Simulated meteorological parameters and turbulence fluxes have been compared with observations through standard statistical measures. Model results show acceptable behavior, but no particular scheme produces best performance for all locations and parameters. All PBL schemes underestimate near surface air temperatures over the Tibetan Plateau. By investigating the surface energy budget components, the results suggest that downward longwave radiation and sensible heat flux are the main factors causing the lower near surface temperature. Because the downward longwave radiation and sensible heat flux are respectively affected by atmosphere moisture and land-atmosphere coupling, improvements in water vapor distribution and land-atmosphere energy exchange is meaningful for better presentation of PBL physical processes over the central Tibetan Plateau.

  8. Greenhouse gas scenario sensitivity and uncertainties in precipitation projections for central Belgium

    Science.gov (United States)

    Van Uytven, E.; Willems, P.

    2018-03-01

    Climate change impact assessment on meteorological variables involves large uncertainties as a result of incomplete knowledge on the future greenhouse gas concentrations and climate model physics, next to the inherent internal variability of the climate system. Given that the alteration in greenhouse gas concentrations is the driver for the change, one expects the impacts to be highly dependent on the considered greenhouse gas scenario (GHS). In this study, we denote this behavior as GHS sensitivity. Due to the climate model related uncertainties, this sensitivity is, at local scale, not always that strong as expected. This paper aims to study the GHS sensitivity and its contributing role to climate scenarios for a case study in Belgium. An ensemble of 160 CMIP5 climate model runs is considered and climate change signals are studied for precipitation accumulation, daily precipitation intensities and wet day frequencies. This was done for the different seasons of the year and the scenario periods 2011-2040, 2031-2060, 2051-2081 and 2071-2100. By means of variance decomposition, the total variance in the climate change signals was separated in the contribution of the differences in GHSs and the other model-related uncertainty sources. These contributions were found dependent on the variable and season. Following the time of emergence concept, the GHS uncertainty contribution is found dependent on the time horizon and increases over time. For the most distinct time horizon (2071-2100), the climate model uncertainty accounts for the largest uncertainty contribution. The GHS differences explain up to 18% of the total variance in the climate change signals. The results point further at the importance of the climate model ensemble design, specifically the ensemble size and the combination of climate models, whereupon climate scenarios are based. The numerical noise, introduced at scales smaller than the skillful scale, e.g. at local scale, was not considered in this study.

  9. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats.

    Science.gov (United States)

    Machnik, Agnes; Dahlmann, Anke; Kopp, Christoph; Goss, Jennifer; Wagner, Hubertus; van Rooijen, Nico; Eckardt, Kai-Uwe; Müller, Dominik N; Park, Joon-Keun; Luft, Friedrich C; Kerjaschki, Dontscho; Titze, Jens

    2010-03-01

    We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain

  10. Antibiotic sensitivity pattern of bacteria from diabetic foot infections Haji Adam Malik central general hospital

    Science.gov (United States)

    Bulolo, B. A.; Pase, M. A.; Ginting, F.

    2018-03-01

    Increasing rate of Diabetic Foot Infections (DFIs) caused by multi-drug-resistance pathogens plays a huge role in the duration of hospitalization, morbidity, and mortality of diabetic patients. The aim of the study is to assess the antibiotic sensitivity pattern of bacteria in DFIs and causative microorganisms. Using cross-sectional retrospective study, data were collected from medical records of DFIs patients previously hospitalized atHaji Adam Malik Hospital, Medan from January to July 2017. 33 patients met the criteria and got enrolled in the study. The classification of DFIs was evaluated according to Wagner’s Classification. Evaluation of antibiotic sensitivity and identification of causative microorganisms were performed in standard microbiologic methods. The most common grade of DFIs was Grade-4 (48.5%), followed by Grade-3 (39.4%) and Grade-5 (9.1%). A total of 12 pathogens were identified. The most common infecting microorganism isolated on pus cultures was Klebsiella pneumonia (33.3%), followed by Escherichia coli (24.2%), Acinetobacter baumanni (12.1%), and Staphylococcus aureus (9.1%). Frequent susceptible antibiotics were Amikacin (88.8%), Imipenem (87%), Meropenem (84.6%), Erythromycin (75%), and Cefoperazone/Sulbactam (68.9%). DFIs are polymicrobial infections in this study K. pneumonia was the most common cause microorganism.

  11. Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum

    Directory of Open Access Journals (Sweden)

    Biswal Shyam

    2006-12-01

    Full Text Available Abstract Background Lowered sensitivity to the effects of ethanol increases the risk of developing alcoholism. Inbred mouse strains have been useful for the study of the genetic basis of various drug addiction-related phenotypes. Inbred Long-Sleep (ILS and Inbred Short-Sleep (ISS mice differentially express a number of genes thought to be implicated in sensitivity to the effects of ethanol. Concomitantly, there is evidence for a mediating role of cAMP/PKA/CREB signalling in aspects of alcoholism modelled in animals. In this report, the extent to which CREB signalling impacts the differential expression of genes in ILS and ISS mouse cerebella is examined. Results A training dataset for Machine Learning (ML and Exploratory Data Analyses (EDA was generated from promoter region sequences of a set of genes known to be targets of CREB transcription regulation and a set of genes whose transcription regulations are potentially CREB-independent. For each promoter sequence, a vector of size 132, with elements characterizing nucleotide composition features was generated. Genes whose expressions have been previously determined to be increased in ILS or ISS cerebella were identified, and their CREB regulation status predicted using the ML scheme C4.5. The C4.5 learning scheme was used because, of four ML schemes evaluated, it had the lowest predicted error rate. On an independent evaluation set of 21 genes of known CREB regulation status, C4.5 correctly classified 81% of instances with F-measures of 0.87 and 0.67 respectively for the CREB-regulated and CREB-independent classes. Additionally, six out of eight genes previously determined by two independent microarray platforms to be up-regulated in the ILS or ISS cerebellum were predicted by C4.5 to be transcriptionally regulated by CREB. Furthermore, 64% and 52% of a cross-section of other up-regulated cerebellar genes in ILS and ISS mice, respectively, were deemed to be CREB-regulated. Conclusion These

  12. Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism.

    Science.gov (United States)

    Kashyap, Des R; Kuzma, Marcin; Kowalczyk, Dominik A; Gupta, Dipika; Dziarski, Roman

    2017-09-01

    Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn 2+ through influx of extracellular Zn 2+ ) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy. © 2017 John Wiley & Sons Ltd.

  13. Secondary Traumatic Stress Increases Expression of Proteins Implicated in Peripheral and Central Sensitization of Trigeminal Neurons.

    Science.gov (United States)

    Hawkins, J L; Moore, N J; Miley, D; Durham, P L

    2018-03-06

    The pathology of migraine, a common neurological disease, involves sensitization and activation of trigeminal nociceptive neurons to promote hyperalgesia and allodynia during an attack. Migraineurs often exhibit characteristics of a hyperexcitable or hypervigilant nervous system. One of the primary reported risk factors for development of a hyperexcitable trigeminal system is chronic, unmanaged stress and anxiety. While primary traumatic stress is a commonly cited risk factor for many pain conditions, exposure to secondary traumatic stress early in life is also thought to be a contributing risk factor. The goal of this study was to investigate cellular changes within the spinal trigeminal nucleus and trigeminal ganglion mediated by secondary traumatic stress. Male Sprague Dawley rats (sender) were subjected to forced swim testing (primary traumatic stress) and were then housed in close visual, olfactory, and auditory proximity to the breeding male and female rats, pregnant female rats, or female rats and their nursing offspring (all receivers). In response to secondary stress, levels of calcitonin gene-related peptide, active forms of the mitogen activated protein kinases ERK, JNK, and p38, and astrocyte expression of glial fibrillary acidic protein were significantly elevated in the spinal trigeminal nucleus in day 45 offspring when compared to naïve offspring. In addition, increased nuclear expression of ERK and p38 was observed in trigeminal ganglion neurons. Our results demonstrate that secondary traumatic stress promotes cellular events associated with prolonged trigeminal sensitization in the offspring, and provides a mechanism of how early life stress may function as a risk factor for migraine. Copyright © 2018. Published by Elsevier B.V.

  14. Sensitivity experiments of a regional climate model to the different convective schemes over Central Africa

    Science.gov (United States)

    Armand J, K. M.

    2017-12-01

    In this study, version 4 of the regional climate model (RegCM4) is used to perform 6 years simulation including one year for spin-up (from January 2001 to December 2006) over Central Africa using four convective schemes: The Emmanuel scheme (MIT), the Grell scheme with Arakawa-Schulbert closure assumption (GAS), the Grell scheme with Fritsch-Chappell closure assumption (GFC) and the Anthes-Kuo scheme (Kuo). We have investigated the ability of the model to simulate precipitation, surface temperature, wind and aerosols optical depth. Emphasis in the model results were made in December-January-February (DJF) and July-August-September (JAS) periods. Two subregions have been identified for more specific analysis namely: zone 1 which corresponds to the sahel region mainly classified as desert and steppe and zone 2 which is a region spanning the tropical rain forest and is characterised by a bimodal rain regime. We found that regardless of periods or simulated parameters, MIT scheme generally has a tendency to overestimate. The GAS scheme is more suitable in simulating the aforementioned parameters, as well as the diurnal cycle of precipitations everywhere over the study domain irrespective of the season. In JAS, model results are similar in the representation of regional wind circulation. Apart from the MIT scheme, all the convective schemes give the same trends in aerosols optical depth simulations. Additional experiment reveals that the use of BATS instead of Zeng scheme to calculate ocean flux appears to improve the quality of the model simulations.

  15. Dor: aspectos atuais da sensibilização periférica e central Dolor: aspectos actuales de la sensibilización periférica y central Pain: current aspects on peripheral and central sensitization

    Directory of Open Access Journals (Sweden)

    Anita Perpétua Carvalho Rocha

    2007-02-01

    conducción nerviosa central y periférica.BACKGROUND AND OBJECTIVES: Current research has focused on the biochemical and structural plasticity of the nervous system secondary to tissue injury. The mechanisms involved in the transition from acute to chronic pain are complex and involve the interaction of receptor systems and the flow of intracellular ions, second messenger systems, and new synaptic connections. The aim of this article was to discuss the new mechanisms concerning peripheral and central sensitization. CONTENTS: Tissue injury increases the response of nociceptors, known as sensitization or facilitation. These phenomena begin after the local release of inflammatory mediators and the activation of the cells of the immune system or specific receptors in the peripheral and central nervous system. CONCLUSIONS: Tissue and neuronal lesions result in sensitization of the nociceptors and facilitation of the central and peripheral nervous conduction.

  16. ERK potentiates p38 in central sensitization induced by traumatic occlusion.

    Science.gov (United States)

    Jing, Lei; Liu, Xiao-Dong; Yang, Hong-Xu; Zhang, Mian; Wang, Ying; Duan, Li; Zhang, Jing; Lu, Lei; Yang, Ting; Wang, Dong-Mei; Chen, Liang-Wei; Wang, Mei-Qing

    2017-01-06

    This study was to investigate the role of p38 activation via ERK1/2 phosphorylation in neurons and microglia of the spinal trigeminal subnucleus caudalis (Vc) in the promotion of orofacial hyperalgesia induced by unilateral anterior crossbite (UAC) traumatic occlusion in adult rats. U0126, a p-ERK1/2 inhibitor, was injected intracisternally before UAC implant. The effects of the U0126 injection were compared to those following the injection of SB203580, a p-p38 inhibitor. Mechanical hyperalgesia was evaluated via pressure pain threshold measurements. Brain stem tissues were processed for a Western blot analysis to evaluate the activation of ERK1/2 and p38. Double immunofluorescence was also performed to observe the expression of p-ERK1/2 and p-p38 in neurons (labeled by NeuN) and microglia (labeled by OX42). The data showed that UAC caused orofacial hyperalgia ipsilaterally on d1 to d7, peaking on d3 (Pcentral sensitization via the activation of ERK1/2 and p38 in both neurons and microglia in the Vc, potentially impacting the effects of p-ERK1/2 during p38 activation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Sensitivity study of rock mass response to glaciation at Finnsjoen, central Sweden

    International Nuclear Information System (INIS)

    Israelsson, J.; Rosengren, L.; Stephansson, O.

    1992-11-01

    The safety analysis SKB-91 of the Swedish Nuclear Fuel and Waste Management Company (SKB) paid specific attention to the glaciation scenario and related phenomena. In the first phase, Rosengren and Stephansson (1990), used the distinct element computer code UDEC to examine the response of the rock mass in the Finnsjoen area to the processes of glaciation and deglaciation. This report describes the second phase, in which the sensitivity of the results to different in situ stresses and fault zone strength properties have been analyzed. A statistical approach was used to extrapolate the range of in-situ stresses at depth from measured in-situ stresses at shallower depths. Three different linear in-situ stress variations with depth were defined using a 99% confidence interval. For each in-situ stress case, three fault zone strength assumptions were analyzed for an ice loading sequence, involving 3 km, 1 km, 0-1 km (ice wedge) and 0 km of ice thickness. Each combination of in-situ stress and fault zone strength was analyzed with and without an ice lake, situated on top of the ice sheet. Consequently, a total of 18 models were studied. The results indicated significant differences in stress distribution, failure (reactivation) of fault zones, and shear displacement on fault zones for some combinations of in-situ stress, fault zone strength, and ice lake pressure. Based on the results, several preliminary recommendations for repository siting are made, as well as recommendations for further study. (authors)

  18. Highly sensitive KRAS mutation detection from formalin-fixed paraffin-embedded biopsies and circulating tumour cells using wild-type blocking polymerase chain reaction and Sanger sequencing.

    Science.gov (United States)

    Huang, Meggie Mo Chao; Leong, Sai Mun; Chua, Hui Wen; Tucker, Steven; Cheong, Wai Chye; Chiu, Lily; Li, Mo-Huang; Koay, Evelyn Siew-Chuan

    2014-08-01

    Among patients with colorectal cancer (CRC), KRAS mutations were reported to occur in 30-51 % of all cases. CRC patients with KRAS mutations were reported to be non-responsive to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) treatment in many clinical trials. Hence, accurate detection of KRAS mutations would be critical in guiding the use of anti-EGFR MoAb therapies in CRC. In this study, we carried out a detailed investigation of the efficacy of a wild-type (WT) blocking real-time polymerase chain reaction (PCR), employing WT KRAS locked nucleic acid blockers, and Sanger sequencing, for KRAS mutation detection in rare cells. Analyses were first conducted on cell lines to optimize the assay protocol which was subsequently applied to peripheral blood and tissue samples from patients with CRC. The optimized assay provided a superior sensitivity enabling detection of as little as two cells with mutated KRAS in the background of 10(4) WT cells (0.02 %). The feasibility of this assay was further investigated to assess the KRAS status of 45 colorectal tissue samples, which had been tested previously, using a conventional PCR sequencing approach. The analysis showed a mutational discordance between these two methods in 4 of 18 WT cases. Our results present a simple, effective, and robust method for KRAS mutation detection in both paraffin embedded tissues and circulating tumour cells, at single-cell level. The method greatly enhances the detection sensitivity and alleviates the need of exhaustively removing co-enriched contaminating lymphocytes.

  19. Evaluation of two different dosages of local anesthetic solution used for ultrasound-guided femoral nerve block for pain relief and positioning for central neuraxial block in patients of fracture neck of the femur

    Directory of Open Access Journals (Sweden)

    Abhijit A Karmarkar

    2017-01-01

    Full Text Available Introduction: Surgical management of the fracture femur is preferred so as to prevent complications associated with prolonged immobilization. Central neuraxial blockade (CNB is an attractive option for these patients, and an optimal positioning of the patient is a definite requirement. Owing to the pain associated with movement of the fractured limb, it becomes difficult for the patients to give suitable positioning. Femoral nerve block (FNB features as a rescue analgesia so as to provide adequate analgesia for facilitation of satisfactory positioning. Aim: This study aims to compare analgesic effect of two different dosages of local anesthetic (LA solution administered for ultrasonography (USG-guided FNB given to facilitate optimal positioning for conduct of CNB. Materials and Methods: After taking permission from the institutional review board, eighty patients were enrolled in the study to find out the efficacy of dosage of LA solution for FNB in providing pain relief caused by movement of fractured limb during conduct of regional anesthesia. Informed consent was taken. All patients were given USG-guided FNB. Patients were randomized using a computer-generated random number table, into two groups of forty patients each. Group A patients received USG-guided 12 ml of LA solution containing 10 ml lignocaine solution without preservative (2% plus 2 ml normal saline (NS, while Group B patients received USG-guided 15 ml of LA solution containing 13 ml lignocaine solution without preservative (2% plus 2 ml NS for positioning before combined spinal epidural. Results: A total of eighty patients, divided randomly into two groups, were enrolled in the study. Demographics (age, sex, weight, and American Society of Anesthesiologists grades were similar in both groups. No statistical significance was found in the numeric rating scale scores at baseline, zero minutes, 5, and 15 min in both the groups. Conclusion: USG-guided FNB with 12 ml of LA solution was

  20. Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain.

    Science.gov (United States)

    Tikhonova, Maria; Kulikov, Alexander V

    2012-08-31

    Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: [1] BDNF is effective in the treatment of some genetically defined behavioral disturbances; [2] BDNF influences sexually-motivated behavior; [3] Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; [4] ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on

  1. CENTRAL SENSITIZATION AND MEDICATION IN SPINAL CORD INJURED IN-PATIENTS. A CROSS-SECTIONAL CLINICAL STUDY

    DEFF Research Database (Denmark)

    Rosendahl, A; Kasch, Helge

    Background and aims: A major proportion of spinal cord injured subjects (SCIS) suffers from chronic pain. A majority with neuropathic pain, being: shooting, burning and stabbing. Neurological examination reveals signs of central sensitization (CS) e.g. allodynia and hyperalgesia. CS plays...... an important role in maintained neuropathic pain conditions and may lead to or be induced by analgesics. Medication-overuse-headaches (MOH) alter CNS pain processing systems, and the situation is reversed after discontinuation of headache medication. Aim: To determine the occurrence of CS and conditions...... pressure algometry, Von Frey filaments and pinprick test. Patients fulfill McGill Pain Questionnaire and the International SCI pain data-set. All participants undergo examination of the Pressure Pain Detection Threshold, Pressure Pain Tolerance Threshold, Mechanical Detection Threshold, and Wind...

  2. Symptoms of central sensitization and comorbidity for juvenile fibromyalgia in childhood migraine: an observational study in a tertiary headache center.

    Science.gov (United States)

    de Tommaso, Marina; Sciruicchio, Vittorio; Delussi, Marianna; Vecchio, Eleonora; Goffredo, Marvita; Simeone, Michele; Barbaro, Maria Grazia Foschino

    2017-12-01

    Central sensitization is an important epiphenomenon of the adult migraine, clinically expressed by allodynia, pericranial tenderness and comorbidity for fibromyalgia in a relevant number of patients. This study aimed to evaluate the frequency and the clinical characteristics of allodynia, pericranial tenderness, and comorbidity for Juvenile Fibromialgia (JFM) in a cohort of migraine children selected in a tertiary headache center. This was an observational cross-sectional study on 8-15 years old migraine patients. Allodynia was assessed by a questionnaire. Pericranial tenderness and comorbidity for JFM as well as their possible association with poor quality of life and migraine related disability, and with other clinical symptoms as anxiety, depression, sleep disorders and pain catastrophizing, were also evaluated. One hundred and fifty one patients were selected, including chronic migraine (n°47), migraine without aura (n° 92) and migraine with aura (n° 12) sufferers. Allodynia was reported in the 96,6% and pericranial tenderness was observed in the 68.8% of patients. Pericranial tenderness was more severe in patients with more frequent migraine and shorter sleep duration. Allodynia seemed associated with anxiety, pain catastrophizing and high disability scores. Comorbidity for JFM was present in the 0.03% ofpatients. These children presented with a severe depression and a significant reduction of quality of life as compared to the other patients. This study outlined a relevant presence of symptoms of central sensitization among children with migraine. Severe allodynia and comorbidity for JFM seemed to cause a general decline of quality of life, which would suggest the opportunity of a routine assessment of these clinical features.

  3. Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    Science.gov (United States)

    Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F

    2016-09-01

    Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®

  4. Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells.

    Science.gov (United States)

    Corns, Laura F; Johnson, Stuart L; Kros, Corné J; Marcotti, Walter

    2016-01-13

    The transduction of sound into electrical signals depends on mechanically sensitive ion channels in the stereociliary bundle. The molecular composition of this mechanoelectrical transducer (MET) channel is not yet known. Transmembrane channel-like protein isoforms 1 (TMC1) and 2 (TMC2) have been proposed to form part of the MET channel, although their exact roles are still unclear. Using Beethoven (Tmc1(Bth/Bth)) mice, which have an M412K point mutation in TMC1 that adds a positive charge, we found that Ca(2+) permeability and conductance of the MET channel of outer hair cells (OHCs) were reduced. Tmc1(Bth/Bth) OHCs were also less sensitive to block by the permeant MET channel blocker dihydrostreptomycin, whether applied extracellularly or intracellularly. These findings suggest that the amino acid that is mutated in Bth is situated at or near the negatively charged binding site for dihydrostreptomycin within the permeation pore of the channel. We also found that the Ca(2+) dependence of the operating range of the MET channel was altered by the M412K mutation. Depolarization did not increase the resting open probability of the MET current of Tmc1(Bth/Bth) OHCs, whereas raising the intracellular concentration of the Ca(2+) chelator BAPTA caused smaller increases in resting open probability in Bth mutant OHCs than in wild-type control cells. We propose that these observations can be explained by the reduced Ca(2+) permeability of the mutated MET channel indirectly causing the Ca(2+) sensor for adaptation, at or near the intracellular face of the MET channel, to become more sensitive to Ca(2+) influx as a compensatory mechanism. In the auditory system, the hair cells convert sound-induced mechanical movement of the hair bundles atop these cells into electrical signals through the opening of mechanically gated ion channels at the tips of the bundles. Although the nature of these mechanoelectrical transducer (MET) channels is still unclear, recent studies implicate

  5. Baroreflex sensitivity and central hemodynamics after omega-3 polyunsaturated fatty acids supplementation in an animal model of menopause.

    Science.gov (United States)

    Losurdo, Pasquale; Grillo, Andrea; Panizon, Emiliano; Zanetti, Michela; Bardelli, Moreno; Biolo, Gianni; Fabris, Bruno; Carretta, Renzo

    2015-08-01

    Baroreflex sensitivity (BRS) and central arterial function are significantly worsened after menopausal transition. This study tested the hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA) might contribute to prevent these adverse changes in the vascular function of ovariectomized rats, an animal model of experimental menopause. We randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL), sham surgery, normal diet; ovariectomized with normal diet (OVX) and ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d) (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic response to phenylephrine-induced blood pressure increase, while large artery function was estimated by the graphical analysis of the aortic pressure wave (diastolic to systolic pressure-time integral ratio, DTI/STI). Ovariectomy caused a significant decrease in BRS (CTRL: 6.23±0.68ms/mmHg; OVX: 2.85±0.75; pmenopause (OVX+O3: 4.75±0.53; pchanges in DTI/STI ratio seen in OVX (OVX: 3.31±1.72; OVX+O3: 3.83±1.52; pmenopause, treatment with n-3 PUFA normalized central hemodynamics and prevented the decrease in BRS, associated with the reduction of compliance of the arterial wall. These findings suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of postmenopausal vascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Distribution of lithostratigraphic units within the central block of Yucca Mountain, Nevada: A three-dimensional computer-based model, Version YMP.R2.0

    International Nuclear Information System (INIS)

    Buesch, D.C.; Nelson, J.E.; Dickerson, R.P.; Drake, R.M. II; San Juan, C.A.; Spengler, R.W.; Geslin, J.K.; Moyer, T.C.

    1996-01-01

    Yucca Mountain, Nevada is underlain by 14.0 to 11.6 Ma volcanic rocks tilted eastward 3 degree to 20 degree and cut by faults that were primarily active between 12.7 and 11.6 Ma. A three-dimensional computer-based model of the central block of the mountain consists of seven structural subblocks composed of six formations and the interstratified-bedded tuffaceous deposits. Rocks from the 12.7 Ma Tiva Canyon Tuff, which forms most of the exposed rocks on the mountain, to the 13.1 Ma Prow Pass Tuff are modeled with 13 surfaces. Modeled units represent single formations such as the Pah Canyon Tuff, grouped units such as the combination of the Yucca Mountain Tuff with the superjacent bedded tuff, and divisions of the Topopah Spring Tuff such as the crystal-poor vitrophyre interval. The model is based on data from 75 boreholes from which a structure contour map at the base of the Tiva Canyon Tuff and isochore maps for each unit are constructed to serve as primary input. Modeling consists of an iterative cycle that begins with the primary structure-contour map from which isochore values of the subjacent model unit are subtracted to produce the structure contour map on the base of the unit. This new structure contour map forms the input for another cycle of isochore subtraction to produce the next structure contour map. In this method of solids modeling, the model units are presented by surfaces (structure contour maps), and all surfaces are stored in the model. Surfaces can be converted to form volumes of model units with additional effort. This lithostratigraphic and structural model can be used for (1) storing data from, and planning future, site characterization activities, (2) preliminary geometry of units for design of Exploratory Studies Facility and potential repository, and (3) performance assessment evaluations

  7. Dual orexin receptor antagonist 12 inhibits expression of proteins in neurons and glia implicated in peripheral and central sensitization.

    Science.gov (United States)

    Cady, R J; Denson, J E; Sullivan, L Q; Durham, P L

    2014-06-06

    Sensitization and activation of trigeminal nociceptors is implicated in prevalent and debilitating orofacial pain conditions including temporomandibular joint (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate many physiological processes and are reported to modulate nociception. To determine the role of orexins in an inflammatory model of trigeminal activation, the effects of a dual orexin receptor antagonist (DORA-12) on levels of proteins that promote peripheral and central sensitization and changes in nocifensive responses were investigated. In adult male Sprague-Dawley rats, mRNA for orexin receptor 1 (OX₁R) and receptor 2 (OX₂R) were detected in trigeminal ganglia and spinal trigeminal nucleus (STN). OX₁R immunoreactivity was localized primarily in neuronal cell bodies in the V3 region of the ganglion and in laminas I-II of the STN. Animals injected bilaterally with complete Freund's adjuvant (CFA) in the TMJ capsule exhibited increased expression of P-p38, P-ERK, and lba1 in trigeminal ganglia and P-ERK and lba1 in the STN at 2 days post injection. However, levels of each of these proteins in rats receiving daily oral DORA-12 were inhibited to near basal levels. Similarly, administration of DORA-12 on days 3 and 4 post CFA injection in the TMJ effectively inhibited the prolonged stimulated expression of protein kinase A, NFkB, and Iba1 in the STN on day 5 post injection. While injection of CFA mediated a nocifensive response to mechanical stimulation of the orofacial region at 2h and 3 and 5 days post injection, treatment with DORA-12 suppressed the nocifensive response on day 5. Somewhat surprisingly, nocifensive responses were again observed on day 10 post CFA stimulation in the absence of daily DORA-12 administration. Our results provide evidence that DORA-12 can inhibit CFA-induced stimulation of trigeminal sensory neurons by inhibiting expression of proteins associated with sensitization of peripheral and central

  8. Effect of TENS on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Beckwée David

    2012-02-01

    Full Text Available Abstract Background Central sensitization has recently been documented in patients with knee osteoarthritis (OAk. So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients. Methods Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens. Follow-up measurements will be scheduled after a period of 6 and 12 weeks. Discussion Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens. Trial Registration ClinicalTrials.gov: NCT01390285

  9. PMS1077 sensitizes TNF-α induced apoptosis in human prostate cancer cells by blocking NF-κB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Jie Shi

    Full Text Available Our previous studies have demonstrated that PMS1077, a platelet-activating factor (PAF antagonist, could induce apoptosis of Raji cells. However, the mechanism of action has not yet been determined. The nuclear transcription factor-kappa B (NF-κB signaling pathway plays a critical role in tumor cell survival, proliferation, invasion, metastasis, and angiogenesis, so we determined the effects of PMS1077 and its structural analogs on tumor necrosis factor-α (TNF-α induced activation of NF-κB signaling. In this study, we found that PMS1077 inhibited TNF-α induced expression of the NF-κB regulated reporter gene in a dose dependent manner. Western blot assay indicated that PMS1077 suppressed the TNF-α induced inhibitor of κB-α (IκB-α phosphorylation, IκB-α degradation, and p65 phosphorylation. PMS1077 consistently blocked TNF-α induced p65 nuclear translocation as demonstrated in the immunofluorescence assay used. Docking studies by molecular modeling predicted that PMS1077 might interact directly with the IκB kinase-β (IKK-β subunit. These results suggested that PMS1077 might suppress the activation of NF-κB by targeting IKK-β involved in the NF-κB signaling pathway. Finally, we showed that PMS1077 sensitized cells to TNF-α induced apoptosis by suppressing the expression of NF-κB regulated anti-apoptotic genes. Our results reveal a novel function of PMS1077 on the NF-κB signaling pathway and imply that PMS1077 can be considered as an anti-tumor lead compound.

  10. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  11. Rehabilitation of a Young Athlete With Extension-Based Low Back Pain Addressing Motor-Control Impairments and Central Sensitization.

    Science.gov (United States)

    Winslow, John J; Jackson, Mark; Getzin, Andrew; Costello, Michael

    2018-02-01

      To describe the conservative management of a young athlete with extension-based (EB) low back pain (LBP).   We present the case of a 15-year-old female high school gymnast with a 4-year history of EB LBP. Magnetic resonance imaging revealed a healed spondylolysis and significant atrophy with fatty infiltrate of the lumbar multifidi muscles (LMM). She had several courses of outpatient orthopaedic rehabilitation that focused on core muscle strengthening (improving activation and strength of the LMM and transversus abdominus muscle in a neutral pelvic position) without long-lasting improvement. She was unable to tolerate higher levels of training or compete.   The LMM are rich in muscle spindles and provide continuous feedback to the central nervous system about body position. Atrophy and fatty infiltrate of the LMM can compromise neuromuscular function and contribute to dysfunctional movement patterns that place a greater demand on lumbar spine structures. Ongoing motor-control impairments perpetuate nociceptive input, leading to central sensitization.   The athlete had difficulty controlling trunk extension during sport-specific activities; she moved early and to a greater extent in the lumbar spine. The aim of the treatment was to teach the athlete how to control her tendency to overload her lumbar spine when bending backward, thus reducing nociceptive input from lumbar spine structures and desensitizing the nervous system.   Treating EB LBP by addressing motor-control impairments and cognitive-affective factors as opposed to core strengthening.   Activity modification, bracing, and traditional core-strengthening exercises may not be the most appropriate treatment for athletes experiencing EB LBP. Addressing cognitive-affective factors in addition to correcting maladaptive motor behavior and moving in a pain-free range reduces nociceptive input, desensitizes the nervous system, and allows athletes to gain control over their pain.

  12. The effects of protein phosphatase inhibitors on the duration of central sensitization of rat dorsal horn neurons following injection of capsaicin

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    Fang Li

    2006-07-01

    Full Text Available Abstract Protein kinases and phosphatases catalyze opposing reactions of phosphorylation and dephosphorylation, which may modulate the function of crucial signaling proteins in central nervous system. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. To explore the role of protein phosphatase in central sensitization of spinal nociceptive neurons following peripheral noxious stimulation, using electrophysiological recording techniques, we investigated the role of two inhibitors of protein phosphatase type 2A (PP2A, fostriecin and okadaic acid (OA, on the responses of dorsal horn neurons to mechanical stimuli in anesthetized rats following intradermal injection of capsaicin. Central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw. A microdialysis fiber was implanted in the spinal cord dorsal horn for perfusion of ACSF and inhibitors of PP2A, fostriecin and okadaic acid. We found that in ACSF pretreated animals, the responses to innocuous and noxious stimuli following capsaicin injection increased over a period of 15 min after injection and had mostly recovered by 60 min later. However, pre- or post-treatment with the phosphatase inhibitors, fostriecin or OA, significantly enhanced the effects of capsaicin injection by prolonging the responses to more than 3 hours. These results confirm that blockade of protein phosphatase activity may potentiate central sensitization of nociceptive transmission in the spinal cord following capsaicin injection and indicate that protein phosphatase type 2A may be involved in determining the duration of capsaicin-induced central sensitization.

  13. Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

    International Nuclear Information System (INIS)

    Montagne, Axel; Gauberti, Maxime; Jullienne, Amandine; Briens, Aurelien; Docagne, Fabian; Vivien, Denis; Maubert, Eric; Macrez, Richard; Defer, Gilles; Raynaud, Jean-Sebastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit

    2012-01-01

    Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuro-inflammation. (authors)

  14. Thermo-sensitive transition of monomethodoxy poly(ethylene glycol)-block-poly(trimethylene carbonate) films to micellar-like nanoparticles

    NARCIS (Netherlands)

    Zhang Zheng, Z.Z.; Grijpma, Dirk W.; Feijen, Jan

    2006-01-01

    Monomethoxy poly(ethylene glycol)-block-poly(trimethylene carbonate) (mPEG3–PTMC11, Mn of mPEG = 3.1 × 103 and Mn of PTMC = 10.8 × 103 g/mol) was synthesized by ring-opening polymerization of TMC using mPEG3 as an initiator and stannous octoate as a catalyst. The block copolymer has a broad melting

  15. Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord.

    Science.gov (United States)

    Yanagisawa, Yoshikazu; Furue, Hidemasa; Kawamata, Tomoyuki; Uta, Daisuke; Yamamoto, Jun; Furuse, Shingo; Katafuchi, Toshihiko; Imoto, Keiji; Iwamoto, Yukihide; Yoshimura, Megumu

    2010-07-05

    Chronic bone cancer pain is thought to be partly due to central sensitization. Although murine models of bone cancer pain revealed significant neurochemical changes in the spinal cord, it is not known whether this produces functional alterations in spinal sensory synaptic transmission. In this study, we examined excitatory synaptic responses evoked in substantia gelatinosa (SG, lamina II) neurons in spinal cord slices of adult mice bearing bone cancer, using whole-cell voltage-clamp recording techniques. Mice at 14 to 21 days after sarcoma implantation into the femur exhibited hyperalgesia to mechanical stimuli applied to the skin of the ipsilateral hind paw, as well as showing spontaneous and movement evoked pain-related behaviors. SG neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs). The amplitudes of spontaneous EPSCs were significantly larger in cancer-bearing than control mice without any changes in passive membrane properties of SG neurons. In the presence of TTX, the amplitude of miniature EPSCs in SG neurons was increased in cancer-bearing mice and this was observed for cells sampled across a wide range of lumbar segmental levels. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor- and N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs evoked by focal stimulation were also enhanced in cancer-bearing mice. Dorsal root stimulation elicited mono- and/or polysynaptic EPSCs that were caused by the activation of Adelta and/or C afferent fibers in SG neurons from both groups of animals. The number of cells receiving monosynaptic inputs from Adelta and C fibers was not different between the two groups. However, the amplitude of the monosynaptic C fiber-evoked EPSCs and the number of SG neurons receiving polysynaptic inputs from Adelta and C fibers were increased in cancer-bearing mice. These results show that spinal synaptic transmission mediated through Adelta and C fibers is enhanced in the SG across a wide area of

  16. Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord

    Directory of Open Access Journals (Sweden)

    Uta Daisuke

    2010-07-01

    Full Text Available Abstract Background Chronic bone cancer pain is thought to be partly due to central sensitization. Although murine models of bone cancer pain revealed significant neurochemical changes in the spinal cord, it is not known whether this produces functional alterations in spinal sensory synaptic transmission. In this study, we examined excitatory synaptic responses evoked in substantia gelatinosa (SG, lamina II neurons in spinal cord slices of adult mice bearing bone cancer, using whole-cell voltage-clamp recording techniques. Results Mice at 14 to 21 days after sarcoma implantation into the femur exhibited hyperalgesia to mechanical stimuli applied to the skin of the ipsilateral hind paw, as well as showing spontaneous and movement evoked pain-related behaviors. SG neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs. The amplitudes of spontaneous EPSCs were significantly larger in cancer-bearing than control mice without any changes in passive membrane properties of SG neurons. In the presence of TTX, the amplitude of miniature EPSCs in SG neurons was increased in cancer-bearing mice and this was observed for cells sampled across a wide range of lumbar segmental levels. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor- and N-methyl-D-aspartate (NMDA receptor-mediated EPSCs evoked by focal stimulation were also enhanced in cancer-bearing mice. Dorsal root stimulation elicited mono- and/or polysynaptic EPSCs that were caused by the activation of Aδ and/or C afferent fibers in SG neurons from both groups of animals. The number of cells receiving monosynaptic inputs from Aδ and C fibers was not different between the two groups. However, the amplitude of the monosynaptic C fiber-evoked EPSCs and the number of SG neurons receiving polysynaptic inputs from Aδ and C fibers were increased in cancer-bearing mice. Conclusions These results show that spinal synaptic transmission mediated through Aδ and C fibers is

  17. COMPARATIVE ANALYSIS ON EASTERN AND CENTRAL EUROPEAN STUDENTS’ INTERCULTURAL SENSITIVITY. RESEARCH CONDUCTED IN ROMANIA, HUNGARY AND SLOVENIA

    Directory of Open Access Journals (Sweden)

    Hamburg Andrea

    2016-03-01

    Full Text Available The following study is meant to be an extension of and completion to a former research paper entitled “The Role of Foreign Language Teachers in Developing Students’ Intercultural Communication Skills” concluding that students of the University of Oradea, Romania, generally lack intercultural sensitivity and it falls to a great extent to foreign language teachers to change this state of affairs. When the former study came up with proposals for methods of enhancing students’ cultural awareness (see simulation games on cultural differences like Barnga, BaFá BaFá, Randömia Balloon Factory and others, the present study focuses on an international comparison, though limited to only three academic institutions in three countries, regarding Eastern and Central European students’ intercultural sensitivity. The initial idea was to see to what extent students of the University of Oradea, Romania, studying Economics, Medicine and Law dispose of intercultural skills. For this reason a Likert-type scale questionnaire was applied to more than 200 students of the above mentioned faculties. The survey was extended in the second round in Oradea, Romania, also to the Faculty of Environmental Protection and that of Electrical Engineering and Information Technology, respectively to an international level asking students of the University of Debrecen, Hungary and the University of Maribor, Slovenia, the same questions. Although we are aware of the limitations of present study, – only three institutions included in the research, having in Debrecen and Maribor less respondents than in Oradea and only from some fields of study, Slovenian students not getting a Slovenian version of the questionnaire, which may have influenced their level of understanding issues, responses not always being consistent – its results have still an informative value. They confirm the author’s initial hypothesis that in spite of the extended international relations and

  18. Eclogite Facies Relicts and Decompression Assemblages; Evidence for the Exhumation of a Large Coherent Metabasite Block From > 40 km Depth; Central Metamorphic Terrane, Eastern Klamath Mountains, Northern California

    Science.gov (United States)

    Barrow, W. M.; Fairhurst, R. J.; Metcalf, R. V.

    2007-12-01

    Recent exhumation models for eclogite terranes have focused on the exhumation of sialic rocks. Exhumed high pressure terranes are typically > 85% - 90% sialic material with only minor amounts of mafic and ultramafic rock. Most known metabasitic eclogites are blocks in mélange rather than large coherent bodies. The Central Metamorphic terrane (CMt) is a large (~300 km3) coherent, fault-bounded package of metabasites thought to represent a remnant of a downing plate subducted in an intra-oceanic convergent margin. Thermochronology indicates that the CMt was metamorphosed and later accreted to the base of the Trinity ophiolite along the Trinity fault during Early Permian extension (Hbl and Musc 40Ar/39Ar ages of 275 Ma - 294 Ma). Previous work suggested that the peak metamorphic temperatures and pressures were ~650°C and 0.4 to 0.8 GPa (Peacock and Norris, 1989) which is consistent with the amphibolite facies mineral assemblage. Trace element data confirm the NMORB-like composition of CMt metabasite protoliths. Newly discovered relict textures, however, suggest that CMt amphibolites record much deeper subduction burial with subsequent decompression exhumation. A decompression sequence consisting of rutile cores within ilmenite crystals mantled by titanite is observed in CMt amphibolite samples. Zr-in-rutile thermometry (Watson et al., 2006) combined with experimental data for rutile stability in metabasites (Ernst and Lui, 1998) suggests that relict rutile crystals preserve early P-T conditions of ~600°C and > 1.3 GPa consistent with eclogite facies metamorphism. Transition from eclogite facies is further supported by ilmenite-plagioclase-amphibole symplectites suggesting replacement of garnet (Bhowmik and Roy, 2003) during decompression. Amphibole compositions vary significantly and reflect lower grade (low Na, Al, Ti actinolite) overprint of earlier amphibolite facies compositions (high Na, Al, Ti magnesio- hornblende). Application of the Al-Ti hornblende

  19. Psychological Distress and Widespread Pain Contribute to the Variance of the Central Sensitization Inventory: A Cross-Sectional Study in Patients with Chronic Pain.

    Science.gov (United States)

    van Wilgen, Cornelis P; Vuijk, Pieter J; Kregel, Jeroen; Voogt, Lennard; Meeus, Mira; Descheemaeker, Filip; Keizer, Doeke; Nijs, Jo

    2018-02-01

    Central sensitization (CS) implies increased sensitivity of the nervous system, resulting in increased pain sensitivity as well as widespread pain. Recently, the Central Sensitization Inventory (CSI) was developed to assess symptoms of CS and central sensitivity syndromes. The aim of this study was to examine the convergent validity of the CSI by comparing the outcome to psychosocial factors and clinical features of CS. In a cross-sectional explorative study, patients with chronic pain completed multiple questionnaires, including the CSI, Pain Catastrophizing Scale, and Symptom Checklist 90, for psychological distress, duration of pain, intensity of pain, widespread pain, and lateralization of pain. Based on bivariate correlations, relevant predictors of CS were selected and used to fit an exploratory structural equation model (SEM) of CS. In total, 114 patients with chronic pain were included, 56.1% being women. The average pain duration was 88 months. The mean total score on the CSI was 36.09 (15.26). The CSI was strongly related to known contributing and related factors of CS. SEM analysis showed that both psychological distress and widespread pain contributed significantly to the variance in symptoms of CS in patients with chronic pain. In this study, the convergent validity of the CSI was measured with demonstration of a strong relationship between contributing factors and clinical features of CS. These findings of convergent validity, considering former studies of the CSI, underline the use of the questionnaire in the clinical practice. © 2017 World Institute of Pain.

  20. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat

    Directory of Open Access Journals (Sweden)

    Ikeda Hiroshi

    2012-06-01

    Full Text Available Abstract Background The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. Results In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. Conclusions These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

  1. Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization.

    Science.gov (United States)

    Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

    2016-01-01

    Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(pfibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, pFibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (pfibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (pfibromyalgia symptoms and that laparoscopic cholecystectomy produces only a transitory worsening of these symptoms, largely compensated by the long-term improvement/desensitization due to gallbladder removal. This study provides new insights into the role of visceral pain comorbidities and the effects of

  2. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat.

    Science.gov (United States)

    Ikeda, Hiroshi; Kiritoshi, Takaki; Murase, Kazuyuki

    2012-06-15

    The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

  3. Various semiclassical limits of torus conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Alkalaev, Konstantin [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of General and Applied Physics, Moscow Institute of Physics and Technology,Institutskiy per. 7, Dolgoprudnyi, Moscow region, 141700 (Russian Federation); Geiko, Roman [Mathematics Department, National Research University Higher School of Economics,Usacheva str. 6, Moscow, 119048 (Russian Federation); Rappoport, Vladimir [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of Quantum Physics, Institute for Information Transmission Problems,Bolshoy Karetny per. 19, Moscow, 127994 (Russian Federation)

    2017-04-12

    We study four types of one-point torus blocks arising in the large central charge regime. There are the global block, the light block, the heavy-light block, and the linearized classical block, according to different regimes of conformal dimensions. It is shown that the blocks are not independent being connected to each other by various links. We find that the global, light, and heavy-light blocks correspond to three different contractions of the Virasoro algebra. Also, we formulate the c-recursive representation of the one-point torus blocks which is relevant in the semiclassical approximation.

  4. Participation of the central p38 and ERK1/2 pathways in IL-1β-induced sensitization of nociception in rats.

    Science.gov (United States)

    Yang, Kui Y; Bae, Won S; Kim, Min J; Bae, Yong C; Kim, Young J; Kim, Hyun J; Nam, Soon H; Ahn, Dong K

    2013-10-01

    This study examined the participation of central mitogen-activated protein kinases (MAPKs) in the central sensitization produced by a subcutaneous injection of interleukin-1β (IL-1β) in male Sprague-Dawley rats. Formalin-induced responses were evaluated 24h after an IL-1β injection. A subcutaneous injection of 10ng of IL-1β elevated the formalin-induced scratching response significantly in the second phase compared to the vehicle-treated group. Pretreatment with an IL-1 receptor antagonist reduced the IL-1β-induced sensitization. Pretreatment with IL-1β increased the p-ERK and p-p38 expression induced by the formalin injection. Double immunofluorescence data revealed increases in phospho-extracellular signal-regulated kinase (p-ERK) immunoreactive cells that co-localize with neuronal nuclei (NeuN), a neuronal marker, and in phospho-p38 (p-p38) immunoreactive cells that co-localize with NeuN and OX42, a microglia marker. The intracisternal administration of minocycline (50μg), a microglia inhibitor, attenuated the increased formalin-induced scratching responses in the IL-1β-treated rats. The intracisternal administration of PD98059 (1, 10μg), a MEK inhibitor, and SB203580 (1, 5μg), a p38 inhibitor, also attenuated the number of formalin-induced scratches in the second phase in the IL-1β-treated rats. These results suggest that the IL-1β-induced central sensitization of nociception is mediated by the central MAPK pathways, which are activated differentially in the neurons and microglia under inflammatory pain conditions. Therefore, blockade of the MAPK pathways can be as a potential therapeutic target for the central sensitization of inflammatory pain. © 2013 Elsevier Inc. All rights reserved.

  5. c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury?

    Science.gov (United States)

    Gao, Yong-Jing; Ji, Ru-Rong

    2009-01-01

    c-Fos, the protein of the protooncogene c-fos, has been extensively used as a marker for the activation of nociceptive neurons in the spinal cord for more than twenty years since Hunt et al. first reported that peripheral noxious stimulation to a hind paw of rats leads to a marked induction of c-Fos in superficial and deep dorsal horn neurons in 1987. In 1999, Ji et al. reported that phosphorylated extracellular signal-regulated kinase (pERK) is specifically induced by noxious stimulation in superficial dorsal horn neurons. Accumulating evidence indicates that pERK induction or ERK activation in dorsal horn neurons is essential for the development of central sensitization, increased sensitivity of dorsal horn neurons that is responsible for the generation of persistent pain. Further, molecular mechanisms underlying ERK-mediated central sensitization have been revealed. In contrast, direct evidence for c-Fos-mediated central sensitization is not sufficient. After a noxious stimulus (e.g., capsaicin injection) or tissue injury, c-Fos begins to be induced after 30-60 minutes, whereas pERK can be induced within a minute, which can correlate well with the development of pain hypersensitivity. While c-Fos is often induced in the nuclei of neurons, pERK can be induced in different subcellular structures of neurons such as nuclei, cytoplasma, axons, and dendrites. pERK can even be induced in spinal cord microglia and astrocytes after nerve injury. In summary, both c-Fos and pERK can be used as markers for neuronal activation following noxious stimulation and tissue injury, but pERK is much more dynamic and appears to be a better marker for central sensitization.

  6. Semi-automatic spray pyrolysis deposition of thin, transparent, titania films as blocking layers for dye-sensitized and perovskite solar cells

    Czech Academy of Sciences Publication Activity Database

    Krýsová, Hana; Krýsa, J.; Kavan, Ladislav

    2018-01-01

    Roč. 9, APR 2018 (2018), s. 1135-1145 ISSN 2190-4286 R&D Projects: GA ČR GA17-20008S; GA ČR(CZ) GA18-08959s Institutional support: RVO:61388955 Keywords : blocking films * FTO * solar cells Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 3.127, year: 2016

  7. The micellization and dissociation transitions of thermo-, pH- and sugar-sensitive block copolymer investigated by laser light scattering

    Directory of Open Access Journals (Sweden)

    Y. C. Tang

    2012-08-01

    Full Text Available A triple-stimuli responsive polymer, poly(3-acrylamidophenylboronic acid-b-poly(N-isopropylacrylamide (PAAPBA-b-PNIPAM, has been synthesized by reversible addition-fragmentation chain transfer polymerization. Temperature, pH, and fructose induced micellization and dissociation transition of block copolymer was investigated by a combination of static and dynamic laser light scattering. PAAPBA-b-PNIPAM copolymer self-assembles into micelles with PAAPBA block as core and PNIPAM as shell in lower pH aqueous solution at room temperature. Increasing the temperature causes the micelle to shrink due to the dehydration of PNIPAM segments at pH 6.2. After the elevation of solution pH from 6.2 to 10.0, the increase in the hydrophilicity of PAAPBA block leads to an expulsion of unimers from micelles. In addition, the fructose addition further enhances the dissociation of micelles. Our experiments demonstrate that the micelle to unimer transition process proceeds via the step-by-step sequential expulsion of individual chains.

  8. Differences Between Women With Traumatic and Idiopathic Chronic Neck Pain and Women Without Neck Pain: Interrelationships Among Disability, Cognitive Deficits, and Central Sensitization.

    Science.gov (United States)

    Coppieters, Iris; De Pauw, Robby; Kregel, Jeroen; Malfliet, Anneleen; Goubert, Dorien; Lenoir, Dorine; Cagnie, Barbara; Meeus, Mira

    2017-03-01

    To date, a clear differentiation of disability, cognitive deficits, and central sensitization between chronic neck pain of a traumatic nature and that of a nontraumatic nature is lacking. This study aimed to examine differences in disability, cognitive deficits, and central sensitization between women with traumatic and idiopathic (nontraumatic) chronic neck pain and women who were healthy. In addition, interrelationships among these variables were investigated. This was a case-control study. Ninety-five women (28 women who were healthy [controls], 35 women with chronic idiopathic neck pain [CINP], and 32 women with chronic whiplash-associated disorders [CWAD] [traumatic]) were enrolled in the study. First, all participants completed standardized questionnaires to investigate pain-related disability and health-related quality of life. Next, cognitive performance was assessed. Finally, pressure pain thresholds and conditioned pain modulation were examined to investigate central sensitization. Pain-related disability, reduced health-related quality of life, and cognitive deficits were present in participants with CWAD and, to a significantly lesser extent, in participants with CINP. Local hyperalgesia was demonstrated in participants with CWAD and CINP but not in women who were healthy. However, distant hyperalgesia and decreased conditioned pain modulation efficacy were shown only in participants with CWAD; this result is indicative of the presence of central sensitization. Moderate to strong Spearman correlations (ρ=.456-.701) among disability, cognitive deficits, and hyperalgesia (local and distant) were observed in participants with CWAD. In participants with CINP, only local hyperalgesia and subjective cognitive deficits were moderately (ρ=.463) correlated. No conclusions about the causality of the observed correlations can be drawn. This innovative research revealed important differences between women with CWAD and women with CINP and thus provided evidence

  9. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

  10. Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.

    Science.gov (United States)

    Xie, Rou-Gang; Gao, Yong-Jing; Park, Chul-Kyu; Lu, Ning; Luo, Ceng; Wang, Wen-Ting; Wu, Sheng-Xi; Ji, Ru-Rong

    2018-02-01

    Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2 + ) neurons. CCL2 increased NMDA-induced currents in CCR2 + /VGLUT2 + neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.

  11. Micromachining and validation of the scanning acoustic microscope spatial resolution and sensitivity calibration block for 20–230 MHz frequency range

    International Nuclear Information System (INIS)

    Tamulevicius, Tomas; Simatonis, Linas; Ulcinas, Orestas; Tamulevicius, Sigitas; Zukauskas, Egidijus; Rekuviene, Regina; Mazeika, Liudas

    2016-01-01

    Scanning acoustic microscopy (SAM) is used as a routine non-destructive test tool for different diagnostic examinations: detection of defects such as microcracks, delamination, disbonding, inclusions, subsurface features in materials such as pores and cracks. SAM can be operated in a wide frequency range from Megahertz to Gigahertz. SAM measurement spatial resolution is diffraction limited by the wavelength of the acoustic wave in particular medium and also depends on individual transducers geometry. Actual SAM spatial resolution can be determined by measuring calibrated lithographically formed microstructures in high acoustic impedance materials. Numerical acoustic signal simulation method, based on the diffraction approach, was employed for the selection of the calibration block pattern geometry and linear dimensions of the elements. Universal calibration block for SAM operating in a 20–230 MHz frequency range was micromachined in high acoustic impedance ceramic substrates. Differently spaced (from 18 to 185 µm) lines of the same width and different widths (from 17 to 113 µm) but similar spacing lines were imposed in alumina ceramics employing one step lithography process, i.e. femtosecond laser ablation. Proposed SAM calibration pattern linear dimensions were characterized employing optical and scanning electron microscopy. Finally the samples were measured with SAM employing different frequency transducers and results were compared with the numerical simulations. It was obtained that resolution of SAM operating with 230 MHz transducer is not worse than 40 µm. (author)

  12. ESI-VI5, Central St Thomas, U.S. Virgin Islands 2000 (Environmental Sensitivity Index Map)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Environmental Sensitivity Index (ESI) maps are an integral component in oil-spill contingency planning and assessment. They serve as a source of information in the...

  13. Close relation of interpersonal sensitivity with negative core beliefs about the self, the central construct of cognitive vulnerability to depression.

    Science.gov (United States)

    Otani, Koichi; Suzuki, Akihito; Matsumoto, Yoshihiko; Shirata, Toshinori

    2018-05-01

    Interpersonal sensitivity is a personality trait linked with anxious attachment conceptualized in attachment theory. This personality trait is comprised of four components, i.e., interpersonal awareness, separation anxiety, timidity and fragile inner-self, which are measured by the corresponding subscales of the Interpersonal Sensitivity Measure (IPSM). Meanwhile, one study showed that six items of the IPSM tentatively used as negative self-schemas predicted the onset of depression. To clarify if interpersonal sensitivity reflects cognitive vulnerability, we examined the relation of this personality trait with negative core beliefs about the self. The study population consisted of 335 Japanese volunteers. Interpersonal sensitivity was measured by the IPSM, and negative core beliefs about the self were assessed by the negative-self subscale of the Brief Core Schema Scales (BCSS). Multiple regression analysis showed that scores of the four subscales of the IPSM were strongly correlated with those of the negative-self subscale of the BCSS (P < 0.001). Similarly, sequential equation modeling demonstrated that the four components of interpersonal sensitivity were strongly predicted by core beliefs of negative-self (P < 0.001). The present study shows that interpersonal sensitivity is closely related to negative core beliefs about the self, suggesting that this personality trait can be regarded as a cognitive vulnerability to depression. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Apatite fission-track evidence for regional exhumation in the subtropical Eocene, block faulting, and localized fluid flow in east-central Alaska

    Science.gov (United States)

    Dusel-Bacon, Cynthia; Bacon, Charles R.; O'Sullivan, Paul B.; Day, Warren C.

    2016-01-01

    The origin and antiquity of the subdued topography of the Yukon–Tanana Upland (YTU), the physiographic province between the Denali and Tintina faults, are unresolved questions in the geologic history of interior Alaska and adjacent Yukon. We present apatite fission-track (AFT) results for 33 samples from the 2300 km2 western Fortymile district in the YTU in Alaska and propose an exhumation model that is consistent with preservation of volcanic rocks in valleys that requires base level stability of several drainages since latest Cretaceous–Paleocene time. AFT thermochronology indicates widespread cooling below ∼110 °C at ∼56–47 Ma (early Eocene) and ∼44–36 Ma (middle Eocene). Samples with ∼33–27, ∼19, and ∼10 Ma AFT ages, obtained near a major northeast-trending fault zone, apparently reflect hydrothermal fluid flow. Uplift and erosion following ∼107 Ma magmatism exposed plutonic rocks to different extents in various crustal blocks by latest Cretaceous time. We interpret the Eocene AFT ages to suggest that higher elevations were eroded during the Paleogene subtropical climate of the subarctic, while base level remained essentially stable. Tertiary basins outboard of the YTU contain sediment that may account for the required >2 km of removed overburden that was not carried to the sea by the ancestral Yukon River system. We consider a climate driven explanation for the Eocene AFT ages to be most consistent with geologic constraints in concert with block faulting related to translation on the Denali and Tintina faults resulting from oblique subduction along the southern margin of Alaska.

  15. Central amygdala activation of extracellular signal-regulated kinase 1 and age-dependent changes in inflammatory pain sensitivity in mice.

    Science.gov (United States)

    Sadler, Katelyn E; Gartland, Nathan M; Cavanaugh, Jane E; Kolber, Benedict J

    2017-08-01

    Aging populations are more sensitive to noxious stimuli as a result of altered somatosensory systems. In these experiments, we examined pain-like behaviors in young, middle-aged, and old mice during peripheral inflammation to determine if the same sensitivity exists in preclinical animal models. Immediately following injury, middle-aged and old mice exhibited more spontaneous pain-like behaviors than young mice, matching pain prevalence in clinical populations. Middle-aged and old mice also developed persistent mechanical hypersensitivity in the injured paw. Furthermore, old mice developed mechanical hypersensitivity in the noninjured paw suggesting age-dependent changes in central nociceptive systems. To address this end, pain-related protein expression was examined in the central nucleus of the amygdala, a limbic brain region that modulates somatic pain. Following injury, increased phosphorylation of extracellular signal-regulated kinase 1, a protein with known nociceptive functions, was observed in the right central nucleus of the amygdala of old mice and not middle-aged or young animals. These findings suggest that age-dependent changes in supraspinal nociceptive systems may account for increased pain-like behaviors in aging populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats.

    Science.gov (United States)

    Begg, Denovan P; Mul, Joram D; Liu, Min; Reedy, Brianne M; D'Alessio, David A; Seeley, Randy J; Woods, Stephen C

    2013-03-01

    Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

  17. A specific and sensitive method for visualization of tumor necrosis factor in the murine central nervous system

    DEFF Research Database (Denmark)

    Lambertsen, K L; Drøjdahl, N; Owens, T

    2001-01-01

    We present here sensitive, simple and robust methods for detection of tumor necrosis factor (TNF) mRNA and TNF in histological sections and homogenates of brain tissue from mice subjected to focal cerebral ischemia or hippocampal axonal lesioning. Both types of lesions are characterized by induct......We present here sensitive, simple and robust methods for detection of tumor necrosis factor (TNF) mRNA and TNF in histological sections and homogenates of brain tissue from mice subjected to focal cerebral ischemia or hippocampal axonal lesioning. Both types of lesions are characterized...... of individual cells, and can successfully be combined with immunohistochemical procedures. We also describe a sensitive immunohistochemical method for detection of TNF, which can be combined with visualization of an additional antigen. The specificity of the histological procedures are confirmed by RT......-PCR and Western blot analysis on homogenates prepared from microdissected brain regions. Advantages and disadvantages of the methods are discussed with emphasis on the specificity and sensitivity of the histological procedures. Our strategy for detection of TNF mRNA and protein provides a solid basis...

  18. Sensitization of Tumor to {sup 212}Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    Energy Technology Data Exchange (ETDEWEB)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E. [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Brechbiel, Martin W., E-mail: martinwb@mail.nih.gov [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-15

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using {sup 212}Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by {sup 212}Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with {sup 212}Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. {sup 212}Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling.

  19. Sensitization of Tumor to 212Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    International Nuclear Information System (INIS)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2013-01-01

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using 212 Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by 212 Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with 212 Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. 212 Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling

  20. Toward a Spatial Perspective on Business Sustainability: The Role of Central Urban and Environmentally Sensitive Areas in Energy Corporates’ Green Behaviours

    Science.gov (United States)

    Wang, Teng; Liu, Zongrui; Zhou, Li

    2018-02-01

    As one of the most concerned topics in strategic management research, the motivations of energy corporates’ green behaviours are extensively explored by scholars, however, only a few noticed the role of geographic antecedents. To bridge this gap, we argue that energy firms’ green behaviours will be greatly predicted by its location, more specifically, proximity to environmentally sensitive areas and central urban areas. Draw on neo-institutional theory and stakeholder theory, we argue that institutional forces mediate the links between energy corporates’ green behaviours and proximities, while different proximity affects via different institutional logics. The results are discussed along with managerial implications.

  1. Comment on "Cheat-sensitive commitment of a classical bit coded in a block of m ×n round-trip qubits"

    Science.gov (United States)

    He, Guang Ping

    2014-05-01

    We found a cheating strategy for the quantum cheat-sensitive bit commitment protocol proposed in Phys. Rev. A 84, 022308 (2011), 10.1103/PhysRevA.84.022308. It enables the receiver of the commitment to cheat with a probability not less than 1/2, no matter what values are chosen for the security parameters in the protocol. More interestingly, the probability for successful cheating will rise as the number n of the particles used in the protocol increases and will be arbitrarily close to 100% in the limit n →∞.

  2. Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization.

    Science.gov (United States)

    Durham, Paul L

    2016-08-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype.

  3. A sensitivity analysis of central flat-plate photovoltaic systems and implications for national photovoltaics program planning

    Science.gov (United States)

    Crosetti, M. R.

    1985-01-01

    The sensitivity of the National Photovoltaic Research Program goals to changes in individual photovoltaic system parameters is explored. Using the relationship between lifetime cost and system performance parameters, tests were made to see how overall photovoltaic system energy costs are affected by changes in the goals set for module cost and efficiency, system component costs and efficiencies, operation and maintenance costs, and indirect costs. The results are presented in tables and figures for easy reference.

  4. Control of Solid-State Dye-Sensitized Solar Cell Performance by Block-Copolymer-Directed TiO2 Synthesis

    KAUST Repository

    Docampo, Pablo

    2010-04-21

    Hybrid dye-sensitized solar cells are typically composed of mesoporous titania (TiO2), light-harvesting dyes, and organic molecular hole-transporters. Correctly matching the electronic properties of the materials is critical to ensure efficient device operation. In this study, TiO 2 is synthesized in a welldefined morphological confinement that arises from the self-assembly of a diblock copolymer - poly(isoprene-b-ethylene oxide) (Pl-b-PEO). The crystallization environment, tuned by the inorganic (TiO2 mass) to organic (polymer) ratio, is shown to be a decisive factor in determining the distribution of sub-bandgap electronic states and the associated electronic function in solid-state dye-sensitized solar cells. Interestingly, the tuning of the sub-bandgap states does not appear to strongly influence the charge transport and recombination in the devices. However, increasing the depth and breadth of the density of sub-bandgap states correlates well with an increase in photocurrent generation, suggesting that a high density of these sub-bandgap states is critical for efficient photo-induced electron transfer and charge separation. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Clinical Criteria of Central Sensitization in Chronic Pelvic and Perineal Pain (Convergences PP Criteria): Elaboration of a Clinical Evaluation Tool Based on Formal Expert Consensus.

    Science.gov (United States)

    Levesque, Amélie; Riant, Thibault; Ploteau, Stéphane; Rigaud, Jérôme; Labat, Jean-Jacques

    2018-03-07

    The evaluation of chronic pelvic and perineal pain (CPP) is often complex. The patient's description of the pain often appears to be disproportionate to the limited findings on physical examination and/or complementary investigations. The concept of central sensitization may allow better understanding and management of patients with CPP. The aim of this study was to elaborate a clinical evaluation tool designed to simply identify sensitization in pelvic pain. A list of 63 items was submitted to 22 international CPP experts according to the Delphi method. Ten clinical criteria were adopted for the creation of a clinical evaluation tool: 1) pain influenced by bladder filling and/or urination, 2) pain influenced by rectal distension and/or defecation, 3) pain during sexual activity, 4) perineal and/or vulvar pain in response to normally nonpainful stimulation, 5) pelvic trigger points (e.g., in the piriformis, obturator internus, and/or levator ani muscles), 6) pain after urination, 7) pain after defecation, 8) pain after sexual activity, 9) variable (fluctuating) pain intensity and/or variable pain distribution, 10) migraine or tension headaches and/or fibromyalgia and/or chronic fatigue syndrome and/or post-traumatic stress disorder and/or restless legs syndrome and/or temporomandibular joint dysfunction and/or multiple chemical sensitivity.  This process resulted in the elaboration of a clinical evaluation tool designed to identify and appropriately manage patients with CPP comprising a sensitization component.

  6. Linking atmospheric blocking to European temperature extremes in spring

    Science.gov (United States)

    Brunner, Lukas; Hegerl, Gabriele; Steiner, Andrea

    2017-04-01

    The weather in Europe is influenced by a range of dynamical features such as the Atlantic storm tracks, the jet stream, and atmospheric blocking. Blocking describes an atmospheric situation in which a stationary and persistent high pressure system interrupts the climatological flow for several days to weeks. It can trigger cold and warm spells which is of special relevance during the spring season because vegetation is particularly vulnerable to extreme temperatures in the early greening phase. We investigate European cold and warm spells in the 36 springs from 1979 to 2014 in temperature data from the European daily high-resolution gridded dataset (E-OBS) and connect them to blocking derived from geopotential height fields from ERA-Interim. A highly significant link between blocking and both, cold and warm spells is found that changes during spring. Resolving monthly frequencies, we find a shift in the preferred locations of blocking throughout spring. The maximum blocking frequency during cold spells shifts from Scandinavia to the British Isles in March and April. During warm spells it continuously shifts further northward during the spring season. The location of the block is found to be essential for the sign of the relationship. Blocking over the north-eastern Atlantic and over northern Europe is strongly linked to cold conditions, while blocking over central Europe is associated with warm conditions. Consistently the spatial distribution of temperature extremes across Europe is highly sensitive to the occurrence of blocking. More than 80 % of cold spells in south-eastern Europe occur during blocking, compared to less than 30 % in northern Europe. Warm spells show the opposite pattern and more than 70 % co-occur with blocking in northern Europe, compared to less than 30 % in parts of southern Europe. We find considerable interannual variability over the analysis period from 1979 to 2014 but also a decrease in cold spells and an increase in warm spells

  7. Central infusion of ketone bodies modulates body weight and hepatic insulin sensitivity by modifying hypothalamic leptin and insulin signaling pathways in type 2 diabetic rats.

    Science.gov (United States)

    Park, Sunmin; Kim, Da Sol; Daily, James W

    2011-07-15

    Although the effects of ketogenic diets on energy and glucose homeostasis have been controversial, elevation of serum ketone levels by subcutaneous injection of β-hydroxybutyrate (BHB) can improve glucose homeostasis. Ketones may work through the brain; therefore, we evaluated whether the intracerebroventricular (ICV) infusion of β-hydroxybutyrates would also modulate peripheral energy and glucose homeostasis, and through what mechanisms, in diabetic rats fed a high fat diet in short- and long-term studies. Short-term (3h) central injection of BHB (50 μg/h) improved serum glucose levels and peripheral insulin sensitivity compared to the artificial cerebrospinal fluid (CSF) group among 90% pancreatectomized (Px) diabetic rats, but not in non-diabetic Sham rats. In addition to short-term infusion, long-term (28 days) central infusion of BHB (12 μg/h) elevated serum BHB levels. Long-term infusion of BHB potentiated leptin and insulin signaling in the hypothalamus to slightly decrease body weight in Px rats. Central BHB infusion had a greater effect on peripheral glucose metabolism than overall energy metabolism. Hepatic insulin signaling (tyrosine phosphorylation of IRS2→serine phosphorylation of Akt→reduced expression of PEPCK) was potentiated and hepatic glucose production in the hyperinsulinemic state was suppressed in the diabetic rats. In addition, glucose tolerance was improved by central BHB infusion through enhanced whole body glucose disposal rates, but insulin secretion was not affected in the diabetic rats. In conclusion, mild ketosis by central infusion of ketones improves energy and glucose metabolism through the potentiation of leptin and insulin signaling in the hypothalamus of diabetic rats. Copyright © 2011. Published by Elsevier B.V.

  8. Light-Emitting Diode Phototherapy Reduces Nocifensive Behavior Induced by Thermal and Chemical Noxious Stimuli in Mice: Evidence for the Involvement of Capsaicin-Sensitive Central Afferent Fibers.

    Science.gov (United States)

    Pigatto, Glauce Regina; Coelho, Igor Santos; Aquino, Rosane Schenkel; Bauermann, Liliane Freitas; Santos, Adair Roberto Soares

    2017-07-01

    Low-intensity phototherapy using light fonts, like light-emitting diode (LED), in the red to infrared spectrum is a promising alternative for the treatment of pain. However, the underlying mechanisms by which LED phototherapy reduces acute pain are not yet well understood. This study investigated the analgesic effect of multisource LED phototherapy on the acute nocifensive behavior of mice induced by thermal and chemical noxious stimuli. The involvement of central afferent C fibers sensitive to capsaicin in this effect was also investigated. Mice exposed to multisource LED (output power 234, 390, or 780 mW and power density 10.4, 17.3, and 34.6 mW/cm 2 , respectively, from 10 to 30 min of stimulation with a wavelength of 890 nm) showed rapid and significant reductions in formalin- and acetic acid-induced nocifensive behavior. This effect gradually reduced but remained significant for up to 7 h after LED treatment in the last model used. Moreover, LED (390 mW, 17.3 mW/cm 2 /20 min) irradiation also reduced nocifensive behavior in mice due to chemical [endogenous (i.e., glutamate, prostaglandins, and bradykinin) or exogenous (i.e., formalin, acetic acid, TRPs and ASIC agonist, and protein kinase A and C activators)] and thermal (hot plate test) stimuli. Finally, ablating central afferent C fibers abolished LED analgesia. These experimental results indicate that LED phototherapy reduces the acute painful behavior of animals caused by chemical and thermal stimuli and that LED analgesia depends on the integrity of central afferent C fibers sensitive to capsaicin. These findings provide new information regarding the underlying mechanism by which LED phototherapy reduces acute pain. Thus, LED phototherapy may be an important tool for the management of acute pain.

  9. Type 7 adenylyl cyclase is involved in the ethanol and CRF sensitivity of GABAergic synapses in mouse central amygdala

    Directory of Open Access Journals (Sweden)

    Maureen T. Cruz

    2011-01-01

    Full Text Available AbstractThe GABAergic system in the central amygdala (CeA plays a major role in ethanol dependence and in the anxiogenic response to ethanol withdrawal. Previously, we found that both ethanol and corticotropin releasing factor (CRF increase GABAergic transmission in mouse and rat CeA neurons, in part by enhancing the release of GABA via activation of presynaptic CRF1 receptors. CRF1 receptors are coupled to the enzyme adenylyl cyclase (AC, which produces the second messenger cyclic AMP. There are nine isoforms of AC, but we recently found that CRF1 receptors in the pituitary were coupled to the Type 7 AC (AC7. Therefore, using an in vitro electrophysiological approach in brain slices, here we have investigated a possible role of the AC7 signaling pathway in ethanol and CRF effects on CeA GABAergic synapses of genetically modified mice with diminished brain Adcy7 activity (HET compared to their littermate male wild type (WT mice. We found no significant differences in basal membrane properties, mean baseline amplitude of evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs, or paired-pulse facilitation (PPF of GABAA-IPSPs between HET and WT mice. In CeA neurons of WT mice, ethanol superfusion significantly augmented (by 39% GABAA-IPSPs and decreased PPF (by 25%, suggesting increased presynaptic GABA release. However, these effects were absent in HET mice. CRF superfusion also significantly augmented IPSPs (by 38% and decreased PPF (by 23% in WT CeA neurons, and still elicited a significant but smaller (by 13% increase of IPSP amplitude, but no effect on PPF, in HET mice. These electrophysiological data suggest that AC7 plays an important role in ethanol and CRF modulation of presynaptic GABA release in CeA and thus may underlie ethanol-related behaviors such as anxiety and dependence.

  10. Assessment of soil erosion sensitivity and post-timber-harvesting erosion response in a mountain environment of Central Italy

    Science.gov (United States)

    Borrelli, Pasquale; Schütt, Brigitta

    2014-01-01

    This study aimed to assess the effects of forest management on the occurrence of accelerated soil erosion by water. The study site is located in a mountainous area of the Italian Central Apennines. Here, forest harvesting is a widespread forestry activity and is mainly performed on the moderate to steep slopes of the highlands. Through modeling operations based on data on soil properties and direct monitoring of changes in the post-forest-harvesting soil surface level at the hillslope scale, we show that the observed site became prone to soil erosion after human intervention. Indeed, the measured mean soil erosion rate of 49 t ha- 1 yr- 1 for the harvested watershed is about 21 times higher than the rate measured in its neighboring undisturbed forested watershed (2.3 t ha- 1 yr- 1). The erosive response is greatly aggravated by exposing the just-harvested forest, with very limited herbaceous plant cover, to the aggressive attack of the heaviest annual rainfall without adopting any conservation practices. The erosivity of the storms during the first four months of field measurements was 1571 MJ mm h- 1 ha- 1 in total (i.e., from September to December 2008). At the end of the experiment (16 months), 18.8%, 26.1% and 55.1% of the erosion monitoring sites in the harvested watershed recorded variations equal or greater than 0-5, 5-10 and > 10 mm, respectively. This study also provides a quantification of Italian forestland surfaces with the same pedo-lithological characteristics exploited for wood supply. Within a period of ten years (2002-2011), about 9891 ha of coppice forest changes were identified and their potential soil erosion rates modeled.

  11. Source Apportionment of PM2.5 Mass and Optical Attenuation Over an Ecologically Sensitive Zone in Central India by Positive Matrix Factorization

    Science.gov (United States)

    Nirmalkar, J.; Raman, R. S.

    2016-12-01

    Ambient PM2.5 samples (N=366) were collected over an ecologically sensitive zone (Van Vihar National Park) in Bhopal, Central India for two years (01 January, 2012 to 31 December, 2013). Samples were collected using three co-located Mini-Vol® samplers on Teflon, Nylon, and Quartz filter substrates. The aerosol was then chemically characterized for water-soluble inorganic ions, elements, and carbon fractions (elemental carbon and organic carbon) using ion chromatography, ED-XRF, and thermal-optical EC/OC analyzer, respectively. The optical attenuation (at 370 nm and 800 nm) of PM2.5 aerosols was also determined by optical transmissometry (OT-21). The application of Positive matrix factorization (PMF) to a combination of PM2.5 mass, its ions, elements, carbon fractions, and optical attenuation and its outcomes will be discussed.

  12. Cognitive Performance Is Related to Central Sensitization and Health-related Quality of Life in Patients with Chronic Whiplash-Associated Disorders and Fibromyalgia.

    Science.gov (United States)

    Coppieters, Iris; Ickmans, Kelly; Cagnie, Barbara; Nijs, Jo; De Pauw, Robby; Noten, Suzie; Meeus, Mira

    2015-01-01

    A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients. (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups. A case-control study was conducted. The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp. Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]). Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P central pain modulation in healthy controls. Further, significant correlations between

  13. Central Sensitization Is Modulated Following Trigger Point Anesthetization in Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo-Controlled, Crossover Study.

    Science.gov (United States)

    Nystrom, N Ake; Freeman, Michael D

    2018-01-01

    Central sensitization (CS) with low peripheral pain thresholds (PPTs) is a common finding among patients with chronic pain after whiplash (CPWI). While it has been proposed that myofascial myofascial trigger points (MTrPs) may act as modulators of central sensitization, previously reported findings are conflicting and inconclusive. The present study was designed to investigate immediate responsiveness of CS to alterations in nociceptive input. Controlled, double-blind, cross-over. Thirty-one patients with chronic pain (trapezius myalgia) and CS after whiplash. Participants were referred by randomization to group A for injection of a single peripheral pain generator (MTrP or other discrete tender point) with local anesthetic or to group B for sham injection and cross-over. Documentation of PPT (Algometer), maximum jaw opening (caliper), and grip strength (Vigorimeter), as well as subjective overall pain (visual analog scale [VAS]), was made before and after each intervention. Statistical analysis of data (Student's t test, analysis of variance) confirmed that peripheral pain thresholds were significantly higher and maximum jaw opening significantly greater after anesthetizing a focal pain generator in the trapezius, but not after a sham injection. In contrast with the objective variables, subjective generalized pain improved (VAS) after not only an injection of local anesthetic, but also, and to a similar extent, after a sham injection. CS, as expressed by lowered PPT, is a rapidly adjusting physiological response to nociceptive stimuli in some patients with chronic pain after whiplash. PPT are likely modulated by myofascial tender points in selected patients with CS. With reference to the present findings, surgical ablation of MTrPs is discussed as a potential treatment modality for CS. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  14. Long-term actions of interleukin-1beta on delay and tonic firing neurons in rat superficial dorsal horn and their relevance to central sensitization.

    Science.gov (United States)

    Gustafson-Vickers, Sabrina L; Lu, Van B; Lai, Aaron Y; Todd, Kathryn G; Ballanyi, Klaus; Smith, Peter A

    2008-12-17

    Cytokines such as interleukin 1beta (IL-1beta) have been implicated in the development of central sensitization that is characteristic of neuropathic pain. To examine its long-term effect on nociceptive processing, defined medium organotypic cultures of rat spinal cord were exposed to 100 pM IL-1beta for 6-8 d. Interleukin effects in the dorsal horn were examined by whole-cell patch-clamp recording and Ca(2+) imaging techniques. Examination of the cultures with confocal Fluo-4 AM imaging showed that IL-1beta increased the change in intracellular Ca(2+) produced by exposure to 35-50 mM K+. This is consistent with a modest increase in overall dorsal horn excitability. Despite this, IL-1beta did not have a direct effect on rheobase or resting membrane potential nor did it selectively destroy any specific neuronal population. All effects were instead confined to changes in synaptic transmission. A variety of pre- and postsynaptic actions of IL-1beta were seen in five different electrophysiologically-defined neuronal phenotypes. In putative excitatory 'delay' neurons, cytokine treatment increased the amplitude of spontaneous EPSC's (sEPSC) and decreased the frequency of spontaneous IPSC's (sIPSC). These effects would be expected to increase dorsal horn excitability and to facilitate the transfer of nociceptive information. However, other actions of IL-1beta included disinhibition of putative inhibitory 'tonic' neurons and an increase in the amplitude of sIPSC's in 'delay' neurons. Since spinal microglial activation peaks between 3 and 7 days after the initiation of chronic peripheral nerve injury and these cells release IL-1beta at this time, our findings define some of the neurophysiological mechanisms whereby nerve-injury induced release of IL-1beta may contribute to the central sensitization associated with chronic neuropathic pain.

  15. Long-term actions of interleukin-1β on delay and tonic firing neurons in rat superficial dorsal horn and their relevance to central sensitization

    Directory of Open Access Journals (Sweden)

    Ballanyi Klaus

    2008-12-01

    Full Text Available Abstract Background Cytokines such as interleukin 1β (IL-1β have been implicated in the development of central sensitization that is characteristic of neuropathic pain. To examine its long-term effect on nociceptive processing, defined medium organotypic cultures of rat spinal cord were exposed to 100 pM IL-1β for 6–8 d. Interleukin effects in the dorsal horn were examined by whole-cell patch-clamp recording and Ca2+ imaging techniques. Results Examination of the cultures with confocal Fluo-4 AM imaging showed that IL-1β increased the change in intracellular Ca2+ produced by exposure to 35–50 mM K+. This is consistent with a modest increase in overall dorsal horn excitability. Despite this, IL-1β did not have a direct effect on rheobase or resting membrane potential nor did it selectively destroy any specific neuronal population. All effects were instead confined to changes in synaptic transmission. A variety of pre- and postsynaptic actions of IL-1β were seen in five different electrophysiologically-defined neuronal phenotypes. In putative excitatory 'delay' neurons, cytokine treatment increased the amplitude of spontaneous EPSC's (sEPSC and decreased the frequency of spontaneous IPSC's (sIPSC. These effects would be expected to increase dorsal horn excitability and to facilitate the transfer of nociceptive information. However, other actions of IL-1β included disinhibition of putative inhibitory 'tonic' neurons and an increase in the amplitude of sIPSC's in 'delay' neurons. Conclusion Since spinal microglial activation peaks between 3 and 7 days after the initiation of chronic peripheral nerve injury and these cells release IL-1β at this time, our findings define some of the neurophysiological mechanisms whereby nerve-injury induced release of IL-1β may contribute to the central sensitization associated with chronic neuropathic pain.

  16. Central sensitization does not identify patients with carpal tunnel syndrome who are likely to achieve short-term success with physical therapy.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Cleland, Joshua A; Ortega-Santiago, Ricardo; de-la-Llave-Rincon, Ana Isabel; Martínez-Perez, Almudena; Pareja, Juan A

    2010-11-01

    The aim of the current study was to identify whether hyperexcitability of the central nervous system is a prognostic factor for individuals with carpal tunnel syndrome (CTS) likely to experience rapid and clinical self-reported improvement following a physical therapy program including soft tissue mobilization and nerve slider neurodynamic interventions. Women presenting with clinical and electrophysiological findings of CTS were involved in a prospective single-arm trial. Participants underwent a standardized examination and then a physical therapy session. The physical therapy sessions included both soft tissue mobilization directed at the anatomical sites of potential median nerve entrapment and a passive nerve slider neurodynamic technique targeted to the median nerve. Pressure pain thresholds (PPT) over the median, radial and ulnar nerves, C5-C6 zygapophyseal joint, carpal tunnel and tibialis anterior muscle were assessed bilaterally. Additionally, thermal detection and pain thresholds were measured over the carpal tunnel and thenar eminence bilaterally to evaluate central nervous system excitability. Subjects were classified as responders (having achieved a successful outcome) or non-responders based on self-perceived recovery. Variables were entered into a stepwise logistic regression model to determine the most accurate variables for determining prognosis. Data from 72 women were included in the analysis, of which 35 experienced a successful outcome (48.6%). Three variables including PPT over the C5-C6 joint affected side 66 points were identified. If 2 out of 3 variables were present (LR + 14.8), the likelihood of success increased from 48.6 to 93.3%. We identified 3 factors that may be associated with a rapid clinical response to both soft tissue mobilization and nerve slider neurodynamic techniques targeted to the median nerve in women presenting with CTS. Our results support that widespread central sensitization may not be present in women with CTS who

  17. Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-κB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-α and the Fas Ligand.

    Science.gov (United States)

    Harada, Misuzu; Morimoto, Kyoko; Kondo, Tetsuya; Hiramatsu, Reiko; Okina, Yuji; Muko, Ryo; Matsuda, Iyo; Kataoka, Takao

    2017-12-02

    Quinacrine has been used for therapeutic drugs in some clinical settings. In the present study, we demonstrated that quinacrine decreased the expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor (TNF)-α and interleukin-1 (IL-1) α in human lung adenocarcinoma A549 cells. Quinacrine inhibited ICAM-1 mRNA expression and nuclear factor κB (NF-κB)-responsive luciferase reporter activity following a treatment with TNF-α and IL-1α. In the NF-κB signaling pathway, quinacrine did not markedly affect the TNF-α-induced degradation of the inhibitor of NF-κB or the TNF-α-induced phosphorylation of the NF-κB subunit, p65, at Ser-536 and its subsequent translocation to the nucleus. In contrast, a chromatin immunoprecipitation assay showed that quinacrine prevented the binding of p65 to the ICAM-1 promoter following TNF-α stimulation. Moreover, TNF-α and the Fas ligand effectively reduced the viability of A549 cells in the presence of quinacrine only. Quinacrine down-regulated the constitutive and TNF-α-induced expression of c-FLIP and Mcl-1 in A549 cells. These results revealed that quinacrine inhibits ICAM-1 transcription by blocking the DNA binding of p65 and sensitizes A549 cells to TNF-α and the Fas ligand.

  18. Use of the Central Sensitization Inventory (CSI) as a treatment outcome measure for patients with chronic spinal pain disorder in a functional restoration program.

    Science.gov (United States)

    Neblett, Randy; Hartzell, Meredith M; Williams, Mark; Bevers, Kelley R; Mayer, Tom G; Gatchel, Robert J

    2017-12-01

    The Central Sensitization Inventory (CSI) is a valid and reliable patient-reported instrument designed to identify patients whose presenting symptoms may be related to central sensitization (CS). Part A of the CSI measures a full array of 25 somatic and emotional symptoms associated with CS, and Part B asks if patients have previously been diagnosed with one or more specific central sensitivity syndromes (CSSs) and related disorders. The CSI has previously been validated in a group of patients with chronic pain who were screened by a trained psychiatrist for specific CSS diagnoses. It is currently unknown if the CSI can be a useful treatment-outcome assessment tool for patients with chronic spinal pain disorder (CSPD) who are not screened for comorbid CSSs. It is known, however, that previous studies have identified CS-related symptoms, and comorbid CSSs, in subsets of patients with CSPDs. Studies have also shown that CS-related symptoms can be influenced by cognitive and psychosocial factors, including abuse history in both childhood and adulthood, sleep disturbance, catastrophic and fear-avoidant cognitions, and symptoms of depression and anxiety. This study aimed to evaluate CSI scores, and their associations with other clinically relevant psychosocial variables, in a cohort of patients with CSPD who entered and completed a functional restoration program. A retrospective study of prospectively collected data from a cohort study of patients with CSPD, who completed the CSI at admission to, and discharge from, an interdisciplinary function restoration program (FRP) was carried out. A cohort of 763 patients with CSPD comprised the study sample. Clinical interviews evaluated mood disorders and abuse history. A series of self-reported measures evaluated comorbid psychosocial symptoms, including pain intensity, pain-related anxiety, depressive symptoms, somatization symptoms, perceived disability, and sleep disturbance, at FRP admission and discharge. Patients were

  19. Recent developments in paediatric neuraxial blocks

    Directory of Open Access Journals (Sweden)

    Vrushali Chandrashekhar Ponde

    2012-01-01

    Full Text Available Paediatric anaesthesia and paediatric regional anaesthesia are intertwined. Almost all surgeries unless contradicted could be and should be supplemented with a regional block. The main objective of this review is to elaborate on the recent advances of the central neuraxial blocks, such as application of ultrasound guidance and electrical stimulation in the pursuit of safety and an objective end point. This review also takes account of the traditional technique and understand the benefits as well the risk of each as compared with the recent technique. The recent trends in choosing the most appropriate peripheral block for a given surgery thereby sparing the central neuroaxis is considered. A penile block for circumcision or a sciatic block for unilateral foot surgery, rather than caudal epidural would have a better risk benefit equation. Readers will find a special mention on the recent thoughts on continuous epidural analgesia in paediatrics, especially its rise and fall, yet its unique importance. Lastly, the issue of block placements under sedation or general anaesthesia with its implication in this special population is dealt with. We conducted searches in MEDLINE (PubMed and assessed the relevance of the abstracts of citations identified from literature searches. The search was carried out in English, for last 10 years, with the following key words: Recent advances in paediatric regional anaesthesia; ultrasound guidance for central neuraxial blocks in children; role of electrical stimulation in neuraxial blocks in children; complications in neuraxial block. Full-text articles of potentially relevant abstracts were retrieved for further review.

  20. Convergent Validity of the Dutch Central Sensitization Inventory: Associations with Psychophysical Pain Measures, Quality of Life, Disability, and Pain Cognitions in Patients with Chronic Spinal Pain.

    Science.gov (United States)

    Kregel, Jeroen; Schumacher, Charline; Dolphens, Mieke; Malfliet, Anneleen; Goubert, Dorien; Lenoir, Dorine; Cagnie, Barbara; Meeus, Mira; Coppieters, Iris

    2017-12-08

    Symptoms of central sensitization (CS) have been described in patients with chronic spinal pain (CSP). Although a gold standard to diagnose CS is lacking, psychophysical pain measures are often used. The Central Sensitization Inventory (CSI) is proposed as an alternative method and indirect tool for the evaluation of CS symptomatology. The aim of the current study was to evaluate the convergent validity of the CSI by investigating the association with psychophysical pain measures and self-reported measures of current pain intensity, quality of life, disability, and catastrophizing in CSP patients. One hundred sixteen patients with nonspecific CSP were included in the present study. Patients completed the CSI, were subjected to pressure pain thresholds (PPTs) and a conditioned pain modulation (CPM) paradigm, and completed questionnaires for current pain intensity, quality of life, pain disability, and pain catastrophizing. Higher CSI scores were weakly correlated with lower PPTs (-0.276 ≤ r ≤ -0.237; all P ≤ 0.01) and not with CPM efficacy (r = 0.017; P = 0.858). Higher CSI scores were moderately correlated with higher current pain intensity (r = 0.320; P < 0.001), strongly correlated with lower physical (r = -0.617; P < 0.001) and emotional (r = -0.635; P < 0.001) quality of life, and moderately correlated with higher pain disability (r = 0.472; P < 0.001) and higher pain catastrophizing (r = 0.464; P < 0.001). The CSI was weakly associated with PPTs and not with CPM efficacy in CSP patients. Moderate to strong associations were found with current pain intensity, quality of life, disability, and catastrophizing. The current results illustrate that the CSI does not reflect a direct measure of CS, yet is a representation of general distress, possible originating from CS symptoms. © 2017 World Institute of Pain.

  1. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  2. Association Between Symptoms of Central Sensitization and Cognitive Behavioral Factors in People With Chronic Nonspecific Low Back Pain: A Cross-sectional Study.

    Science.gov (United States)

    Huysmans, Eva; Ickmans, Kelly; Van Dyck, Dries; Nijs, Jo; Gidron, Yori; Roussel, Nathalie; Polli, Andrea; Moens, Maarten; Goudman, Lisa; De Kooning, Margot

    2018-02-01

    The objective of this cross-sectional study was to analyze the relationship between symptoms of central sensitization (CS) and important cognitive behavioral and psychosocial factors in a sample of patients with chronic nonspecific low back pain. Participants with chronic nonspecific low back pain for at least 3 months were included in the study. They completed several questionnaires and a functional test. Pearson's correlation was used to analyze associations between symptoms of CS and pain behavior, functioning, pain, pain catastrophizing, kinesiophobia, and illness perceptions. Additionally, a between-group analysis was performed to compare patients with and without clinically relevant symptoms of CS. Data from 38 participants were analyzed. Significant associations were found between symptoms of CS and all other outcomes, especially current pain (r = 0.510, P = .001), mean pain during the past 7 days (r = 0.505, P = .001), and pain catastrophizing (r = 0.518, P = .001). Patients with clinically relevant symptoms of CS scored significantly worse on all outcomes compared with persons without relevant symptoms of CS, except on functioning (P = .128). Symptoms of CS were significantly associated with psychosocial and cognitive behavioral factors. Patients exhibiting a clinically relevant degree of symptoms of CS scored significantly worse on most outcomes, compared with the subgroup of the sample with fewer symptoms of CS. Copyright © 2017. Published by Elsevier Inc.

  3. Robustness and sensitivities of central U.S. summer convection in the super-parameterized CAM: Multi-model intercomparison with a new regional EOF index

    Science.gov (United States)

    Kooperman, Gabriel J.; Pritchard, Michael S.; Somerville, Richard C. J.

    2013-06-01

    Mesoscale convective systems (MCSs) can bring up to 60% of summer rainfall to the central United States but are not simulated by most global climate models. In this study, a new empirical orthogonal function based index is developed to isolate the MCS activity, similar to that developed by Wheeler and Hendon (2004) for the Madden-Julian Oscillation. The index is applied to compactly compare three conventional- and super-parameterized (SP) versions (3.0, 3.5, and 5.0) of the National Center for Atmospheric Research Community Atmosphere Model (CAM). Results show that nocturnal, eastward propagating convection is a robust effect of super-parameterization but is sensitive to its specific implementation. MCS composites based on the index show that in SP-CAM3.5, convective MCS anomalies are unrealistically large scale and concentrated, while surface precipitation is too weak. These aspects of the MCS signal are improved in the latest version (SP-CAM5.0), which uses high-order microphysics.

  4. TNF-alpha neutralizing antibody blocks thermal sensitivity induced by compound 48/80-provoked mast cell degranulation [v2; ref status: indexed, http://f1000r.es/1w5

    Directory of Open Access Journals (Sweden)

    Devavani Chatterjea

    2013-09-01

    Full Text Available Background: Neuro-inflammatory circuits in the tissue regulate the complex pathophysiology of pain. Protective nociceptive pain serves as an early warning system against noxious environmental stimuli. Tissue-resident mast cells orchestrate the increased thermal sensitivity following injection of basic secretagogue compound 48/80 in the hind paw tissues of ND4 mice. Here we investigated the effects of pre-treatment with TNF-α neutralizing antibody on compound 48/80-provoked thermal hyperalgesia. Methods: We treated ND4 Swiss male mice with intravenous anti-TNF-α antibody or vehicle 30 minutes prior to bilateral, intra-plantar compound 48/80 administration and measured changes in the timing of hind paw withdrawal observed subsequent to mice being placed on a 51oC hotplate. We also assessed changes in tissue swelling, TNF-α gene expression and protein abundance, mast cell degranulation, and neutrophil influx in the hind paw tissue. Findings: We found that TNF-α neutralization significantly blocked thermal hyperalgesia, and reduced early tissue swelling. TNF-α neutralization had no significant effect on mast cell degranulation or neutrophil influx into the tissue, however. Moreover, no changes in TNF-α protein or mRNA levels were detected within 3 hours of administration of compound 48/80. Interpretation:  The neutralizing antibodies likely target pre-formed TNF-α including that stored in the granules of tissue-resident mast cells. Pre-formed TNF-α, released upon degranulation, has immediate effects on nociceptive signaling prior to the induction of neutrophil influx. These early effects on nociceptors are abrogated by TNF-α blockade, resulting in compromised nociceptive withdrawal responses to acute, harmful environmental stimuli.

  5. TNF-alpha neutralizing antibody blocks thermal sensitivity induced by compound 48/80-provoked mast cell degranulation [v1; ref status: indexed, http://f1000r.es/1mq

    Directory of Open Access Journals (Sweden)

    Devavani Chatterjea

    2013-08-01

    Full Text Available Background:  Neuro-inflammatory circuits in the tissue regulate the complex pathophysiology of pain.  Protective nociceptive pain serves as an early warning system against noxious environmental stimuli.  Tissue-resident mast cells orchestrate the increased thermal sensitivity following injection of basic secretagogue compound 48/80 in the hind paw tissues of ND4 mice.  Here we investigated the effects of pre-treatment with TNF-α neutralizing antibody on compound 48/80-provoked thermal hyperalgesia.  Methods:  We treated ND4 Swiss male mice with intravenous anti-TNF-α antibody or vehicle 30 minutes prior to bilateral, intra-plantar compound 48/80 administration and measured changes in the timing of hind paw withdrawal observed subsequent to mice being placed on a 51oC hotplate.  We also assessed changes in tissue swelling, TNF-α gene expression and protein abundance, mast cell degranulation, and neutrophil influx in the hind paw tissue.  Findings:  We found that TNF-α neutralization significantly blocked thermal hyperalgesia, and reduced early tissue swelling. TNF-α neutralization had no significant effect on mast cell degranulation or neutrophil influx into the tissue, however.  Moreover, no changes in TNF-α protein or mRNA levels were detected within 3 hours of administration of compound 48/80.  Interpretation:  The neutralizing antibodies likely target pre-formed TNF-α including that stored in the granules of tissue-resident mast cells. Pre-formed TNF-α, released upon degranulation, has immediate effects on nociceptive signaling prior to the induction of neutrophil influx.  These direct effects on nociceptors are abrogated by TNF-α blockade resulting in compromised nociceptive withdrawal responses to acute, harmful environmental stimuli.

  6. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  7. GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.

    Science.gov (United States)

    Besson, Marie; Matthey, Alain; Daali, Youssef; Poncet, Antoine; Vuilleumier, Pascal; Vuillemier, Pascal; Curatolo, Michele; Zeilhofer, Hanns Ulrich; Desmeules, Jules

    2015-03-01

    Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain. Tolterodine (TLT) was used as an active placebo. The primary outcome parameter was a change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH), which was monitored for 8 hours after drug application. Sedative effects were assessed in parallel to antihyperalgesia. Compared with TLT, recovery from hyperalgesia was significantly faster in the CBZ and CLN groups (P = 0.009). At the time point of maximum effect, the rate of recovery from hyperalgesia was accelerated by CBZ and CLN, relative to placebo by 15.7% (95% confidence interval [CI] 0.8-30.5), P = 0.040, and 28.6% (95% CI 4.5-52.6), P = 0.022, respectively. Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.

  8. Calcium Release Mediated by Redox-Sensitive RyR2 Channels Has a Central Role in Hippocampal Structural Plasticity and Spatial Memory.

    Science.gov (United States)

    More, Jamileth Y; Bruna, Barbara A; Lobos, Pedro E; Galaz, José L; Figueroa, Paula L; Namias, Silvia; Sánchez, Gina L; Barrientos, Genaro C; Valdés, José L; Paula-Lima, Andrea C; Hidalgo, Cecilia; Adasme, Tatiana

    2018-03-01

    Previous studies indicate that hippocampal synaptic plasticity and spatial memory processes entail calcium release from intracellular stores mediated by ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca 2+ release is central for the dendritic spine remodeling induced by brain-derived neurotrophic factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading to memory-associated protein synthesis and structural plasticity. To examine if upregulation of ryanodine receptor type-2 (RyR2) channels and the spine remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and to test if RyR2 downregulation affects BDNF-induced spine remodeling and spatial memory. Downregulation of RyR2 expression (short hairpin RNA [shRNA]) in primary hippocampal neurons, or inhibition of nitric oxide synthase (NOS) or NADPH oxidase, prevented agonist-mediated RyR-mediated Ca 2+ release, whereas BDNF promoted cytoplasmic ROS generation. RyR2 downregulation or inhibitors of N-methyl-d-aspartate (NMDA) receptors, or NOS or of NADPH oxidase type-2 (NOX2) prevented RyR2 upregulation and the spine remodeling induced by BDNF, as did incubation with the antioxidant agent N-acetyl l-cysteine. In addition, intrahippocampal injection of RyR2-directed antisense oligodeoxynucleotides, which caused significant RyR2 downregulation, caused conspicuous defects in a memorized spatial memory task. The present novel results emphasize the key role of redox-sensitive Ca 2+ release mediated by RyR2 channels for hippocampal structural plasticity and spatial memory. Based on these combined results, we propose (i) that BDNF-induced RyR2-mediated Ca 2+ release and ROS generation via NOS/NOX2 are strictly required for the dendritic spine remodeling and the RyR2 upregulation induced by BDNF, and (ii) that RyR2 channel expression is crucial for spatial memory processes. Antioxid. Redox Signal. 00, 000-000.

  9. Incidence and Antimicrobial Sensitivity Profiles of Normal Conjunctiva Bacterial Flora in the Central Area of China: A Hospital-Based Study

    Directory of Open Access Journals (Sweden)

    Hua Tao

    2017-05-01

    Full Text Available Objective: To study the distribution and patterns of resistance to antimicrobial agents of normal conjunctival bacteria.Materials and Methods: Conjunctival specimens were collected from 8,224 patients and then cultured, which underwent antimicrobial susceptibility test following standard methods. Patients with infectious symptoms such as erythema or oedema and those using systemic or topical antibiotics within 1 month were excluded.Results: In this study, the incidence of isolated bacteria was 24.2%. The middle aged group of 41–65 years presented the lowest rate of bacterial isolation which was 19.4%, while the highest isolation rate (83.1% was found in patients in the age range of 0–6 years. In every age group, the incidence of bacterial isolation in men was higher than that in women. The top 3 most commonly isolated micro-organisms were Staphylococcus epidermidis (39.7%, Streptococcus pneumoniae (4.5%, and Staphylococcus aureus (2.7%, of which about 83.1% S. aureus were isolated in the group of 0-6 years. We found that coagulase-negative Staphylococcus (CONS were more resistant to penicillin, macrolides, clindamycin and sulfonamides with the rate ranging from 57.9 to 90.8%, which were highly susceptible to vancomycin, linezolid, rifampin, tetracyclines, and aminoglycosides. Contrasting to CONS, the general resistance rate of S. aureus was significantly lower. Additionally, Streptococcus was susceptible well to the majority of antimicrobial agents, while highly resistant to macrolides and tetracyclines with the rate >80%.Conclusions: In conclusion, our study revealed the incidence and antimicrobial sensitivity profiles of normal conjunctiva bacterial flora in the central area of China, which could be useful in the prevention of ocular infections. Importantly, our data could be used to guide the selection of appropriate prophylactic agents.

  10. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord.

    Science.gov (United States)

    Kawasaki, Yasuhiko; Zhang, Ling; Cheng, Jen-Kun; Ji, Ru-Rong

    2008-05-14

    Central sensitization, increased sensitivity in spinal cord dorsal horn neurons after injuries, plays an essential role in the induction and maintenance of chronic pain. However, synaptic mechanisms underlying central sensitization are incompletely known. Growing evidence suggests that proinflammatory cytokines (PICs), such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha), are induced in the spinal cord under various injury conditions and contribute to pain hypersensitivity. Using patch-clamp recordings in lamina II neurons of isolated spinal cord slices, we compared the effects of IL-1beta, IL-6, and TNFalpha on excitatory and inhibitory synaptic transmission. Whereas TNFalpha enhanced the frequency of spontaneous EPSCs (sEPSCs), IL-6 reduced the frequency of spontaneous IPSCs (sIPSCs). Notably, IL-1beta both enhanced the frequency and amplitude of sEPSCs and reduced the frequency and amplitude of sIPSCs. Consistently, TNFalpha and IL-1beta enhanced AMPA- or NMDA-induced currents, and IL-1beta and IL-6 suppressed GABA- and glycine-induced currents. Furthermore, all the PICs increased cAMP response element-binding protein (CREB) phosphorylation in superficial dorsal horn neurons and produced heat hyperalgesia after spinal injection. Surprisingly, soluble IL-6 receptor (sIL-6R) produced initial decrease of sEPSCs, followed by increase of sEPSCs and CREB phosphorylation. Spinal injection of sIL-6R also induced heat hyperalgesia that was potentiated by coadministration with IL-6. Together, our data have demonstrated that PICs induce central sensitization and hyperalgesia via distinct and overlapping synaptic mechanisms in superficial dorsal horn neurons either by increasing excitatory synaptic transmission or by decreasing inhibitory synaptic transmission. PICs may further induce long-term synaptic plasticity through CREB-mediated gene transcription. Blockade of PIC signaling could be an effective way to suppress

  11. The Central Sensitization Inventory validated and adapted for a Brazilian population: psychometric properties and its relationship with brain-derived neurotrophic factor.

    Science.gov (United States)

    Caumo, Wolnei; Antunes, Luciana C; Elkfury, Jéssica Lorenzzi; Herbstrith, Evelyn G; Busanello Sipmann, Raquel; Souza, Andressa; Torres, Iraci Ls; Souza Dos Santos, Vinicius; Neblett, Randy

    2017-01-01

    The primary aim was to assess the psychometric properties (including internal consistency, construct validity, reproducibility, and factor structure) of the Central Sensitization Inventory (CSI), adapted and validated for a Brazilian population (CSI-BP). Additionally, we evaluated the relationship between the CSI-BP and the serum brain-derived neurotrophic factor (BDNF) and determined if the symptoms elicited by the CSI-BP discriminate between subjects who do/do not respond to the conditioned pain modulation (CPM) task, as assessed by change in numeric pain scale (0-10) score. A cross-sectional study was conducted in a pain clinic in a tertiary teaching hospital. A total of 222 adults with chronic musculoskeletal pain and 63 healthy control subjects completed the CSI-BP and the Brazilian Portuguese pain-catastrophizing scale (BP-PCS). A team of experts translated the CSI according to the international guidelines. Test-retest, item analysis, convergent validity, and factor analysis were performed. Later, a random subsample (n=77) was used to correlate the CSI-BP adjusted index with change in numeric pain-scale score during the CPM task and a BDNF blood sample. The CSI-BP presented strong psychometric properties (test-retest reliability 0.91, Cronbach's α =0.91). Confirmatory factor analysis yielded a four-factor structure, supporting the original English version. The CSI-BP adjusted index showed moderate positive correlation with the BP-PCS, and classified more than 80% of patients correctly vs healthy controls. Serum BDNF levels explained 27% of the variation in the CSI-BP adjusted index. Subjects with impairment in the descending modulatory system had higher CSI-BP adjusted index scores than subjects who responded normally to the CPM task: 49.35 (12.1) vs 39.5 (12.33), respectively ( P <0.05). The CSI-BP was found to be a psychometrically strong and reliable instrument, with primary evidence of validity. Higher scores on the CSI-BP were correlated positively with

  12. Fire suppression has led to greater drought-sensitivity in dry conifer forests: tree-ring carbon isotope evidence from Central Oregon

    Science.gov (United States)

    Voelker, S.; Merschel, A. G.; Meinzer, F. C.; Spies, T. A.; Still, C. J.

    2016-12-01

    Mortality events of economically and ecologically important conifers have been widespread across Western North America over recent decades. Many of these events have been linked to "global change-type droughts" characterized by greater temperatures and evaporative demand. In parallel, since the early to mid- 20th century, increasing atmospheric [CO2] has been shown to increase the water use efficiency (WUE) of trees worldwide while conifer forests in western North America have become denser after the advent of modern fire suppression efforts. Therefore, competing hypotheses include that conifer forests have experienced 1) less drought stress due to water savings from increased WUE, 2) more drought stress due to increased demand for water in dense forests with greater leaf area index, or 3) unchanging stress because these two factors have cancelled each other out. To provide a test of these hypotheses we used inter-annual latewood carbon isotope discrimination, Δ13C, across a dry mixed-conifer forest landscape of central Oregon in the rain shadow of the Cascade Mountains. The forests are dominated by old-growth ponderosa pines (Pinus ponderosa) and younger and fire-intolerant grand firs (Abies grandis). Dendrochronological dating of tree establishment and fires scars established sharp declines in fire frequency and associated increases in the densities of grand fir since the early 1900s. Δ13C data for ponderosa pine and grand fir spanned 1830-2013 and 1900-2013, respectively. For our analyses these years were split into periods of high fire frequency (1830-1900), moderate fire frequency (1901-1956) and fire-exclusion (1957-2013). Comparisons of Δ13C to reconstructed Palmer Drought Severity Index values for the same years revealed that leaf gas exchange of both species has been more sensitive to drought during the recent fire-exclusion period compared to previous periods when surface fires kept tree densities much lower. Similar research is needed elsewhere to

  13. First measurements of ambient aerosol over an ecologically sensitive zone in Central India: Relationships between PM2.5 mass, its optical properties, and meteorology.

    Science.gov (United States)

    Sunder Raman, Ramya; Kumar, Samresh

    2016-04-15

    PM2.5 mass and its optical properties were measured over an ecologically sensitive zone in Central India between January and December, 2012. Meteorological parameters including temperature, relative humidity, wind speed, wind direction, and barometric pressure were also monitored. During the study period, the PM2.5 (fine PM) concentration ranged between 3.2μgm(-3) and 193.9μgm(-3) with a median concentration of 31.4μgm(-3). The attenuation coefficients, βATN at 370nm, 550nm, and 880nm had median values of 104.5Mm(-1), 79.2Mm(-1), and 59.8Mm(-1), respectively. Further, the dry scattering coefficient, βSCAT at 550nm had a median value of 17.1Mm(-1) while the absorption coefficient βABS at 550nm had a median value of 61.2Mm(-1). The relationship between fine PM mass and attenuation coefficients showed pronounced seasonality. Scattering, absorption, and attenuation coefficient at different wavelengths were all well correlated with fine PM mass only during the post-monsoon season (October, November, and December). The highest correlation (r(2)=0.81) was between fine PM mass and βSCAT at 550nm during post-monsoon season. During this season, the mass scattering efficiency (σSCAT) was 1.44m(2)g(-1). Thus, monitoring optical properties all year round, as a surrogate for fine PM mass was found unsuitable for the study location. In order to assess the relationships between fine PM mass and its optical properties and meteorological parameters, multiple linear regression (MLR) models were fitted for each season, with fine PM mass as the dependent variable. Such a model fitted for the post-monsoon season explained over 88% of the variability in fine PM mass. However, the MLR models were able to explain only 31 and 32% of the variability in fine PM during pre-monsoon (March, April, and May) and monsoon (June, July, August, and September) seasons, respectively. During the winter (January and February) season, the MLR model explained 54% of the PM2.5 variability. Copyright

  14. PERIPHERAL BLOCK ANESTHESIA OF UPPER EXTREMITY AND ITS COMPLICATIONS

    OpenAIRE

    Hakan Tapar; Mustafa Suren; Ziya Kaya; Semih Arici; Serkan Karaman; Mursel Kahveci

    2012-01-01

    Successful peripheral blocks and selection of appropriate technique according to surgery is possible with a good knowledge of anatomy. Regional peripheral block anesthesia of upper extremity which applied by single injection to plexus brachialis is the most recommended method of anesthesia in daily surgical procedures. The most important advantages of peripheral nerve blocks which are type of regional anesthesia according to general anesthesia and central blocks are less effect ...

  15. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    A new 3-parameter family of homogeneous 2-by-2 block shifts is described. These are the first examples of irreducible homogeneous bilateral block shifts of block size larger than 1. Author Affiliations. Adam Korányi1. Department of Mathematics, The Graduate Center, City University of New York, New York, NY 10016, USA ...

  16. 76 FR 38533 - Alphabetical Listings: Specially Designated Nationals and Blocked Persons; Blocked Vessels...

    Science.gov (United States)

    2011-06-30

    ... procedure, Banks, Banking, Blocking of assets. For the reasons set forth in the preamble and under the... ISLAMI IRAN (a.k.a. BANK MARKAZI IRAN; a.k.a. CENTRAL BANK OF IRAN; a.k.a. CENTRAL BANK OF THE ISLAMIC...

  17. p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Andersen, Klaus Ejner; Bruze, Magnus

    2009-01-01

    BACKGROUND: Positive patch test reactions to p-phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary 'tattoos'. Cross-sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe...

  18. U-Pb age and Hf isotopic data of detrital zircons from the Devonian and Carboniferous sandstones in Yimin area, NE China: New evidences to the collision timing between the Xing'an and Erguna blocks in eastern segment of Central Asian Orogenic Belt

    Science.gov (United States)

    Han, Guoqing; Liu, Yongjiang; Neubauer, Franz; Bartel, Esther; Genser, Johann; Feng, Zhiqiang; Zhang, Li; Yang, Mingchun

    2015-01-01

    New U-Pb age data and Hf isotope systematics on zircons from Middle Devonian and Lower Carboniferous units from NE China provide evidence for the depositional age of these poorly constrained units as well as for the timing of the collision between the Erguna (Ergun in some references) and Xing'an blocks in the eastern end of Central Asian Orogenic Belt (CAOB). The detrital zircons from the Devonian and Carboniferous sandstones yielded similar age spectra in probability diagrams showing three distinct peaks at ∼450 Ma, ∼500 Ma and ∼540 Ma, respectively, along with Proterozoic and Archean age groups, except for a relatively young age population at ∼360 Ma detected for zircons from the Hongshuiquan Fm. The dating results suggest that the depositional time of the Niqiuhe Fm. should be younger than Late Silurian, as indicated by the youngest 422-Ma detrital zircon from this Fm., and that of the Hongshuiguan Fm. with a youngest detrital age of ca. 338 Ma, is younger than Middle Mississippian (Visean), which is in accordance with those inferred from biostratigraphic data. These dominant age groups are widely found in the Erguna and Xing'an blocks, it is suggested that the sediments of the studied sandstones from Niuqiuhe and Hongshuiquan Fms come mainly from the Erguna and Xing'an blocks. The εHf (t) value of dated zircons from our sandstones has a wide range (-21 to 16), which shows a mixed signature of that from Paleozoic granitoids in Xing'an block (6-17) and Erguna block (-2 to 6), indicating that Erguna and Xing'an blocks had connected before the Middle Devonian deposition of the Niqiuhe Fm. (422 ± 5 Ma). Combined with the age data, we suggest that the Erguna and Xing'an blocks started to accrete at ∼540 Ma, reached the peak of collision at ∼500 Ma, and went into the post-collision stage from ∼490 to ∼450 Ma. The study provides more evidences and constraints for the early Paleozoic evolutions of the inter-continental block amalgamations and

  19. Blocked Randomization with Randomly Selected Block Sizes

    Directory of Open Access Journals (Sweden)

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  20. Blocked randomization with randomly selected block sizes.

    Science.gov (United States)

    Efird, Jimmy

    2011-01-01

    When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  1. 31 CFR 595.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.301 Blocked account; blocked property. The terms blocked account and blocked...

  2. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...

  3. In defense of weight phobia as the central organizing motive in anorexia nervosa: historical and cultural arguments for a culture-sensitive psychological conception.

    Science.gov (United States)

    Habermas, T

    1996-05-01

    Recently several proposals at dropping weight phobia as the central criterion for the differential diagnosis of anorexia nervosa have been advanced, aiming at establishing a new diagnostic category including any self-induced weight loss. The validity of weight phobia as a diagnostic criterion is defended. After summarizing clinical arguments, four groups of culturally or historically remote cases of self-induced weight loss or refusal of food are analyzed in regard to the presence of weight phobia and clinical similarity to modern anorexia nervosa (extreme fasting in the Third World, in the European late Middle Ages, early modern times, and late 19th century). It is demonstrated that modern Western anorexia nervosa with weight phobia is clearly distinct from other groups of cases of extreme fasting without weight phobia. It is concluded that the psychological motive of weight phobia should remain the central criterion for the differential diagnosis of anorexia nervosa.

  4. Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

    Science.gov (United States)

    Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

    2016-11-01

    Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A practical block detector for a depth encoding PET camera

    International Nuclear Information System (INIS)

    Rogers, J.G.; Moisan, C.; Hoskinson, E.M.

    1995-10-01

    The depth-of-interaction effect in block detectors degrades the image resolution in commercial PET cameras and impedes the natural evolution of smaller, less expensive cameras. A method for correcting the measured position of each detected gamma ray by measuring its depth-of-interaction was tested and found to recover 38% of the lost resolution in a table-top 50 cm diameter camera. To obtain the desired depth sensitivity, standard commercial detectors were modified by a simple and practical process, which is suitable for mass production of the detectors. The impact of the detectors modifications on central image resolution and on the ability of the camera to correct for object scatter were also measured. (authors)

  6. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Homogeneous bilateral block shifts. ADAM KORÁNYI. Department of Mathematics, The Graduate Center, City University of New York,. New York, NY 10016, USA. E-mail: Adam.Koranyi@lehman.cuny.edu. MS received 18 January 2013. Abstract. A new 3-parameter family of homogeneous 2-by-2 block shifts is described.

  7. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix.

  8. Control rod blocking monitor

    International Nuclear Information System (INIS)

    Suzuki, Shigeru.

    1993-01-01

    The number of times for setting up a control rod blocking monitor of a BWR type power plant is remarkably reduced to mitigate operator's burden. In the control rod blocking monitor, trip levels, as a judging standard upon outputting control rod blocking inhibition signals, are set up stepwise depending on the power level around control rods put to blocking control. The present invention comprises an allowance judging means capable of setting up trip levels for each of power levels corresponding to a plurality of control rods at once if the power levels are within the set up allowable range. With such a constitution, the set up allowable range is determined previously in the allowance judging means. Accordingly, when a gang blocking is conducted to control rods, if power levels around the control rods are increased at once into the set up allowable range, the trip levels for each of the control rods are set up at once. (I.S.)

  9. Predictability of blocking

    International Nuclear Information System (INIS)

    Tosi, E.; Ruti, P.; Tibaldi, S.; D'Andrea, F.

    1994-01-01

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  10. The mixed block/event-related design.

    Science.gov (United States)

    Petersen, Steven E; Dubis, Joseph W

    2012-08-15

    Neuroimaging studies began using block design and event-related design experiments. While providing many insights into brain functions, these fMRI design types ignore components of the BOLD signal that can teach us additional elements. The development of the mixed block/event-related fMRI design allowed for a fuller characterization of nonlinear and time-sensitive neuronal responses: for example, the interaction between block and event related factors and the simultaneous extraction of transient activity related to trials and block transitions and sustained activity related to task-level processing. This review traces the origins of the mixed block/event-related design from conceptual precursors to a seminal paper and on to subsequent studies using the method. The review also comments on aspects of the experimental design that must be considered when attempting to use the mixed block/event-related design. When taking into account these considerations, the mixed block/event-related design allows fuller utilization of the BOLD signal allowing deeper interpretation of how regions of the brain function on multiple timescales. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Sensitivity of stable isotope ratios of tree-rings of Silver fir (Abies alba Mill.) in Franconia (Central Germany) to climate and environmental changes

    Science.gov (United States)

    Boettger, T.; Haupt, M.; Friedrich, M.

    2012-04-01

    We constructed 1000-year long carbon and oxygen isotope chronologies of Silver fir (Abies alba Mill.) from the temperate region of Franconia (northern Bavaria, Central Germany) with the aim to carry out the climate reconstructions by using of multivariate models. The annual variations of isotope signals in firs were strong influenced by airborne pollutants in the second half of 20th century: the linear responses of 13C; 18O and 2H signals to SO2, O3 and dust concentrations were high significant. Therefore, we used the long meteorological data set, were the disturbed period could be excluded for climate reconstructions. In this case, carbon isotopes correspond most to spring/summer climate conditions as April to August mean temperatures and June/July precipitation amount, oxygen show the strongest correlation to the July relative air humidity and to the April to August mean temperatures. The correlations between tree-ring signals and summer climate are high (p

  12. 31 CFR 594.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.301 Blocked account; blocked property. The terms blocked account and...

  13. Bundle Branch Block

    Science.gov (United States)

    ... 2015. Bundle branch block Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  14. Blocked Urethral Valves

    Science.gov (United States)

    ... the penis. Rarely, small membranes form across the urethra in boys early in pregnancy, and they can block the flow of urine out of the bladder. These membranes are called posterior urethral valves and can have life-threatening consequences ...

  15. Optoelectronics using block copolymers.

    Energy Technology Data Exchange (ETDEWEB)

    Botiz, I.; Darling, S. B.; Center for Nanoscale Materials

    2010-05-01

    Block copolymers, either as semiconductors themselves or as structure directors, are emerging as a promising class of materials for understanding and controlling processes associated with both photovoltaic energy conversion and light emitting devices.

  16. A high fat diet enhances the sensitivity of chick adipose tissue to the effects of centrally injected neuropeptide Y on gene expression of adipogenesis-associated factors.

    Science.gov (United States)

    Wang, Guoqing; Williams, Carli A; McConn, Betty R; Cline, Mark A; Gilbert, Elizabeth R

    2017-09-01

    The purpose of this study was to determine how dietary macronutrient composition and exogenous neuropeptide Y (NPY) affect mRNA abundance of factors associated with lipid metabolism in chick adipose tissue. Chicks were fed one of three isocaloric (3000kcal metabolizable energy (ME)/kg) diets after hatch: high carbohydrate (HC; control), high fat (HF; 30% of ME from soybean oil) or high protein (HP; 25% crude protein). On day 4 post-hatch, vehicle or 0.2nmol of NPY was injected intracerebroventricularly and abdominal and subcutaneous fat depots collected 1h later. In abdominal fat, mRNA abundance of peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid binding protein 4 (FABP4) increased after NPY injection in HF diet-fed chicks. NPY injection decreased expression of PPARγ and sterol regulatory element-binding transcription factor 1 (SREBP1) in the subcutaneous fat of HC diet-fed chicks, whereas SREBP1 expression was increased in the subcutaneous fat of HF diet-fed chicks after NPY injection. An acutely increased central concentration of NPY in chicks affects adipose tissue physiology in a depot- and diet-dependent manner. The chick may serve as a model to understand the relationship between diet and the brain-fat axis' role in maintaining whole body energy homeostasis, as well as to understand metabolic distinctions among fat depots. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Molecular detection and sensitivity to antibiotics and bacteriocins of pathogens isolated from bovine mastitis in family dairy herds of central Mexico.

    Science.gov (United States)

    León-Galván, Ma Fabiola; Barboza-Corona, José E; Lechuga-Arana, A Arianna; Valencia-Posadas, Mauricio; Aguayo, Daniel D; Cedillo-Pelaez, Carlos; Martínez-Ortega, Erika A; Gutierrez-Chavez, Abner J

    2015-01-01

    Thirty-two farms (n = 535 cows) located in the state of Guanajuato, Mexico, were sampled. Pathogens from bovine subclinical mastitis (SCM) and clinical mastitis (CLM) were identified by 16S rDNA and the sensitivity to both antibiotics and bacteriocins of Bacillus thuringiensis was tested. Forty-six milk samples were selected for their positive California Mastitis Test (CMT) (≥3) and any abnormality in the udder or milk. The frequency of SCM and CLM was 39.1% and 9.3%, respectively. Averages for test day milk yield (MY), lactation number (LN), herd size (HS), and number of days in milk (DM) were 20.6 kg, 2.8 lactations, 16.7 animals, and 164.1 days, respectively. MY was dependent on dairy herd (DH), LN, HS, and DM (P resistant to penicillin, clindamycin, ampicillin, and cefotaxime. Bacteriocins synthesized by Bacillus thuringiensis inhibited the growth of multiantibiotic resistance bacteria such as S. agnetis, S. equorum, Streptococcus uberis, Brevibacterium stationis, and Brachybacterium conglomeratum, but they were not active against S. sciuri, a microorganism that showed an 84% resistance to antibiotics tested in this study.

  18. 1/N expansions for central potentials revisited in the light of hypervirial and Hellmann-Feynman theorems and the principle of minimal sensitivity

    International Nuclear Information System (INIS)

    Kwato Njock, M.G.; Bona, Z.; Nsangou, M.; Nana Engo, S.G.; Oumarou, B.

    1999-02-01

    The hypervirial and Hellmann-Feynman theorems are used in the methods of 1/N expansion to construct Rayleigh-Schroedinger perturbation expansion for bound-state energy eigenvalues of spherical symmetric potentials. A new iteration procedure of calculating correction terms of arbitrarily high orders is obtained for any kind of 1/N expansion. The recurrence formulas for three variants of the 1/N expansion are considered in this work, namely, the 1/n expansion, the shifted and unshifted 1/N expansions which are applied to the Gaussian and Patil potentials. As a result, their credibility could be reliably judged when account is taken of high order terms of the eigenenergies. It is also found that there is a distinct advantage in using the shifted 1/N expansion over the two other versions. However, the shifted 1/N expansion diverges for s states and in certain cases is not applicable as far as complicated potentials are concerned. In an effort to solve these problems we have incorporated the principle of minimal sensitivity in the shifted 1/N expansion as a first step toward extending the scope of applicability of that technique, and then we have tested the obtained approach to some unfavorable cases of the Patil and Hellmann potentials. The agreement between our numerical calculations and reference data is quite satisfactory. (author)

  19. Molecular Detection and Sensitivity to Antibiotics and Bacteriocins of Pathogens Isolated from Bovine Mastitis in Family Dairy Herds of Central Mexico

    Science.gov (United States)

    León-Galván, Ma. Fabiola; Barboza-Corona, José E.; Lechuga-Arana, A. Arianna; Valencia-Posadas, Mauricio; Aguayo, Daniel D.; Cedillo-Pelaez, Carlos; Martínez-Ortega, Erika A.; Gutierrez-Chavez, Abner J.

    2015-01-01

    Thirty-two farms (n = 535 cows) located in the state of Guanajuato, Mexico, were sampled. Pathogens from bovine subclinical mastitis (SCM) and clinical mastitis (CLM) were identified by 16S rDNA and the sensitivity to both antibiotics and bacteriocins of Bacillus thuringiensis was tested. Forty-six milk samples were selected for their positive California Mastitis Test (CMT) (≥3) and any abnormality in the udder or milk. The frequency of SCM and CLM was 39.1% and 9.3%, respectively. Averages for test day milk yield (MY), lactation number (LN), herd size (HS), and number of days in milk (DM) were 20.6 kg, 2.8 lactations, 16.7 animals, and 164.1 days, respectively. MY was dependent on dairy herd (DH), LN, HS, and DM (P < 0.01), and correlations between udder quarters from the CMT were around 0.49 (P < 0.01). Coagulase-negative staphylococci were mainly identified, as well as Staphylococcus aureus, Streptococcus uberis, Brevibacterium stationis, B. conglomeratum, and Staphylococcus agnetis. Bacterial isolates were resistant to penicillin, clindamycin, ampicillin, and cefotaxime. Bacteriocins synthesized by Bacillus thuringiensis inhibited the growth of multiantibiotic resistance bacteria such as S. agnetis, S. equorum, Streptococcus uberis, Brevibacterium stationis, and Brachybacterium conglomeratum, but they were not active against S. sciuri, a microorganism that showed an 84% resistance to antibiotics tested in this study. PMID:25815326

  20. Spinal μ-opioid receptor-sensitive lower limb muscle afferents determine corticospinal responsiveness and promote central fatigue in upper limb muscle.

    Science.gov (United States)

    Sidhu, Simranjit K; Weavil, Joshua C; Venturelli, Massimo; Garten, Ryan S; Rossman, Matthew J; Richardson, Russell S; Gmelch, Benjamin S; Morgan, David E; Amann, Markus

    2014-11-15

    We investigated the influence of group III/IV lower limb muscle afferents on the development of supraspinal fatigue and the responsiveness of corticospinal projections to an arm muscle. Eight males performed constant-load leg cycling exercise (80% peak power output) for 30 s (non-fatiguing) and to exhaustion (∼9 min; fatiguing) both under control conditions and with lumbar intrathecal fentanyl impairing feedback from μ-opioid receptor-sensitive lower limb muscle afferents. Voluntary activation (VA) of elbow flexors was assessed via transcranial magnetic stimulation (TMS) during maximum voluntary contraction (MVC) and corticospinal responsiveness was monitored via TMS-evoked potentials (MEPs) during a 25% MVC. Accompanied by a significant 5 ± 1% reduction in VA from pre- to post-exercise, elbow flexor MVC progressively decreased during the fatiguing trial (P muscle afferents, MVC and VA remained unchanged during fatiguing exercise (P > 0.3). MEPs decreased by 36 ± 6% (P lower corticospinal responsiveness during this short bout (P muscle fatigue, group III/IV-mediated leg muscle afferents facilitate responsiveness of the motor pathway to upper limb flexor muscles. By contrast, in the presence of cycling-induced leg fatigue, group III/IV locomotor muscle afferents facilitate supraspinal fatigue in remote muscle not involved in the exercise and disfacilitate, or inhibit, the responsiveness of corticospinal projections to upper limb muscles.

  1. Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia

    Science.gov (United States)

    Gao, Yong-Jing; Ji, Ru-Rong

    2010-01-01

    Activation of extracellular signal-regulated kinase (ERK) in spinal cord neurons could serve as a marker for sensitization of dorsal horn neurons in persistent pain. ERK is normally activated by high-threshold noxious stimuli. We investigated how low-threshold mechanical stimuli could activate ERK after complete Freund’s adjuvant (CFA)-induced inflammation. Unilateral injection of CFA induced ipsilateral heat hyperalgesia and bilateral mechanical allodynia. CFA-induced ERK activation in ipsilateral dorsal horn neurons declined after 2 days. Interestingly, low threshold mechanical stimulation given by light touch either on the inflamed paw or the contralateral non-inflamed paw dramatically increased ERK phosphorylation (pERK) in the dorsal horn ipsilateral to touch stimulation. Notably, light touch induced pERK mainly in superficial neurons in laminae I-IIo. Intrathecal administration of the astroglial toxin L-α-aminoadipate (L-α-AA) on post-CFA day 2 reversed CFA-induced bilateral mechanical allodynia but not heat hyperalgesia. Furthermore, L-α-AA, the glial inhibitor fluorocitrate, and a peptide inhibitor of c-Jun N-terminal Kinase (JNK) all reduced light touch-evoked ERK activation ipsilateral to touch. Collectively, these data suggest that (a) ERK can be activated in superficial dorsal horn neurons by low threshold mechanical stimulation under pathological condition and (b) ERK activation by light touch is associated with mechanical allodynia and requires an astrocyte network. PMID:20722971

  2. Multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Arendt-Nielsen, Lars; Kupers, Ron

    2013-01-01

    BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor...

  3. Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system.

    Science.gov (United States)

    Wynne, P M; Puig, S I; Martin, G E; Treistman, S N

    2009-06-01

    Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies and dendrites reside in the hypothalamus, physically separated from their nerve terminals in the neurohypophysis, provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins. Using electrophysiological and immunohistochemical techniques, we characterized the large-conductance calcium-activated potassium (BK) channel in each of the three primary compartments (soma, dendrite, and terminal) of HNS neurons. We found that dendritic BK channels, in common with somatic channels but in contrast to nerve terminal channels, are insensitive to iberiotoxin. Furthermore, analysis of dendritic BK channel gating kinetics indicates that they, like somatic channels, have fast activation kinetics, in contrast to the slow gating of terminal channels. Dendritic and somatic channels are also more sensitive to calcium and have a greater conductance than terminal channels. Finally, although terminal BK channels are highly potentiated by ethanol, somatic and dendritic channels are insensitive to the drug. The biophysical and pharmacological properties of somatic and dendritic versus nerve terminal channels are consistent with the characteristics of exogenously expressed alphabeta1 versus alphabeta4 channels, respectively. Therefore, one possible explanation for our findings is a selective distribution of auxiliary beta1 subunits to the somatic and dendritic compartments and beta4 to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively.

  4. Right bundle branch block

    DEFF Research Database (Denmark)

    Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse

    2013-01-01

    AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included.......5%/2.3% in women, P Right bundle branch block was associated with significantly...... increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated...

  5. E-Block: A Tangible Programming Tool with Graphical Blocks

    OpenAIRE

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

  6. PERIPHERAL BLOCK ANESTHESIA OF UPPER EXTREMITY AND ITS COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Hakan Tapar

    2012-09-01

    Full Text Available Successful peripheral blocks and selection of appropriate technique according to surgery is possible with a good knowledge of anatomy. Regional peripheral block anesthesia of upper extremity which applied by single injection to plexus brachialis is the most recommended method of anesthesia in daily surgical procedures. The most important advantages of peripheral nerve blocks which are type of regional anesthesia according to general anesthesia and central blocks are less effect to respiration and hemodynamics and shortness of recovery time. If a plexus brachialis catheter is placed, control of pain is provided without using systemic narcotic analgesic. With these advantages; rare life threatening potential complications can be seen which are pneumothorax, hematoma, neuritis, allergy, systemic and neurologic complications. In this compilation we aimed to review again the complications of upper extremity nerve blocks according to block type. [J Contemp Med 2012; 2(3.000: 195-200

  7. Contaminated soil concrete blocks

    NARCIS (Netherlands)

    de Korte, A.C.J.; Brouwers, Jos; Limbachiya, Mukesh C.; Kew, Hsein Y.

    2009-01-01

    According to Dutch law the contaminated soil needs to be remediated or immobilised. The main focus in this article is the design of concrete blocks, containing contaminated soil, that are suitable for large production, financial feasible and meets all technical and environmental requirements. In

  8. Making Block Grants Accountable.

    Science.gov (United States)

    Chelimsky, Eleanor

    Methods of accountability are presented in considering the Reagan administration plan to consolidate 84 federal health, education and social service grants into six block grant areas and to cut overall funding. After matching aspects of public criticism with proposal objectives, a rationale is developed for building elements of accountability into…

  9. Linoleum Block Printing Revisited.

    Science.gov (United States)

    Chetelat, Frank J.

    1980-01-01

    The author discusses practical considerations of teaching linoleum block printing in the elementary grades (tool use, materials, motivation) and outlines a sequence of design concepts in this area for the primary, intermediate and junior high grades. A short list of books and audiovisual aids is appended. (SJL)

  10. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal

    1999-09-01

    Full Text Available This study examined the effects of a tri-schedule on the academic achievement of students in a high school. The tri-schedule consists of traditional, 4x4 block, and hybrid schedules running at the same time in the same high school. Effectiveness of the schedules was determined from the state mandated test of basic skills in reading, language, and mathematics. Students who were in a particular schedule their freshman year were tested at the beginning of their sophomore year. A statistical ANCOVA test was performed using the schedule types as independent variables and cognitive skill index and GPA as covariates. For reading and language, there was no statistically significant difference in test results. There was a statistical difference mathematics-computation. Block mathematics is an ideal format for obtaining more credits in mathematics, but the block format does little for mathematics achievement and conceptual understanding. The results have content specific implications for schools, administrations, and school boards who are considering block scheduling adoption.

  11. Coding with Blockly

    CERN Document Server

    Lovett, Amber

    2017-01-01

    "Blockly is a fun, graphical programming language designed to get kids interested in creating their own computer programs. Through simple text written to foster creativity and problem solving, students will the art of innovation. Large, colorful images show students how to complete activities. Additional tools, including a glossary and an index, help students learn new vocabulary and locate information."-- Provided by publisher.

  12. [Masquerading bundle branch block].

    Science.gov (United States)

    Kukla, Piotr; Baranchuk, Adrian; Jastrzębski, Marek; Bryniarski, Leszek

    2014-01-01

    We here describe a surface 12-lead electrocardiogram (ECG) of a 72-year-old female with a prior history of breast cancer and chemotherapy-induced cardiomyopathy. An echocardiogram revealed left ventricular dysfunction, ejection fraction of 23%, with mild enlarged left ventricle. The 12-lead ECG showed atrial fibrillation with a mean heart rate of about 100 bpm, QRS duration 160 ms, QT interval 400 ms, right bundle branch block (RBBB) and left anterior fascicular block (LAFB). The combination of RBBB features in the precordial leads and LAFB features in the limb leads is known as ''masquerading bundle branch block''. In most cases of RBBB and LAFB, the QRS axis deviation is located between - 80 to -120 degrees. Rarely, when predominant left ventricular forces are present, the QRS axis deviation is near about -90 degrees, turning the pattern into an atypical form. In a situation of RBBB associated with LAFB, the S wave can be absent or very small in lead I. Such a situation is the result of not only purely LAFB but also with left ventricular hypertrophy and/or focal block due to scar (extensive anterior myocardial infarction) or fibrosis (cardiomyopathy). Sometimes, this specific ECG pattern is mistaken for LBBB. RBBB with LAFB may imitate LBBB either in the limb leads (known as 'standard masquerading' - absence of S wave in lead I), or in the precordial leads (called 'precordial masquerading' - absence of S wave in leads V₅ and V₆). Our ECG showed both these types of masquerading bundle branch block - absence of S wave in lead I and in leads V₅ and V₆.

  13. SUPERFICIAL CERVICAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari

    2014-01-01

    Full Text Available Superficial cervical plexus block is one of the regional anesthesia in  neck were limited to thesuperficial fascia. Anesthesia is used to relieve pain caused either during or after the surgery iscompleted. This technique can be done by landmark or with ultrasound guiding. The midpointof posterior border of the Sternocleidomastoid was identified and the prosedure done on thatplace or on the level of cartilage cricoid.

  14. Change Around the Block?

    Science.gov (United States)

    Berlin, Joey

    2017-04-01

    Proponents of a block grant or per-capita cap trumpet them as vehicles for the federal government to give the states a capped amount of funding for Medicaid that legislatures would effectively distribute how they see fit. Questions abound as to what capped Medicaid funding would look like, and what effect it would have on the current Medicaid-eligible population, covered services, and physician payments.

  15. Managing access block.

    Science.gov (United States)

    Cameron, Peter; Scown, Paul; Campbell, Donald

    2002-01-01

    There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

  16. Sensitization of neurons in the central nucleus of the amygdala via the decreased GABAergic inhibition contributes to the development of neuropathic pain-related anxiety-like behaviors in rats.

    Science.gov (United States)

    Jiang, Hong; Fang, Dong; Kong, Ling-Yu; Jin, Zi-Run; Cai, Jie; Kang, Xue-Jing; Wan, You; Xing, Guo-Gang

    2014-10-04

    Despite high prevalence of anxiety accompanying with chronic pain, the mechanisms underlying pain-related anxiety are largely unknown. With its well-documented role in pain and emotion processing, the amygdala may act as a key player in pathogenesis of neuropathic pain-related anxiety. Pain-related plasticity and sensitization of CeA (central nucleus of the amygdala) neurons have been shown in several models of chronic pain. In addition, firing pattern of neurons with spike output can powerfully affect functional output of the brain nucleus, and GABAergic neurons are crucial in the modulation of neuronal excitability. In this study, we first investigated whether pain-related plasticity (e.g. alteration of neuronal firing patterns) and sensitization of CeA neurons contribute to nerve injury-evoked anxiety in neuropathic rats. Furthermore, we explored whether GABAergic disinhibition is responsible for regulating firing patterns and intrinsic excitabilities of CeA neurons as well as for pain-related anxiety in neuropathic rats. We discovered that spinal nerve ligation (SNL) produced neuropathic pain-related anxiety-like behaviors in rats, which could be specifically inhibited by intra-CeA administration of anti-anxiety drug diazepam. Moreover, we found potentiated plasticity and sensitization of CeA neurons in SNL-induced anxiety rats, of which including: 1) increased burst firing pattern and early-adapting firing pattern; 2) increased spike frequency and intrinsic excitability; 3) increased amplitude of both after-depolarized-potential (ADP) and sub-threshold membrane potential oscillation. In addition, we observed a remarkable reduction of GABAergic inhibition in CeA neurons in SNL-induced anxiety rats, which was proved to be important for altered firing patterns and hyperexcitability of CeA neurons, thereby greatly contributing to the development of neuropathic pain-related anxiety. Accordantly, activation of GABAergic inhibition by intra-CeA administration of

  17. Paving block study : final report.

    Science.gov (United States)

    1971-10-01

    The Louisiana Department of Highways has conducted field tests with an experimental revetment consisting of cellular concrete revetment blocks used in conjunction with plastic filter cloth and/or vegetation such as grass or vines. The precast blocks ...

  18. Habitat Blocks and Wildlife Corridors

    Data.gov (United States)

    Vermont Center for Geographic Information — Habitat blocks are areas of contiguous forest and other natural habitats that are unfragmented by roads, development, or agriculture. Vermonts habitat blocks are...

  19. Demographic Data - MDC_Block

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade Census 2000 Blocks. Census blocks are areas bounded on all sides by visible and/or invisible features shown on a map prepared...

  20. Blocking the Hawking radiation

    DEFF Research Database (Denmark)

    Autzen, M.; Kouvaris, C.

    2014-01-01

    grows after its formation (and eventually destroys the star) instead of evaporating. The fate of the black hole is dictated by the two opposite mechanics, i.e., accretion of nuclear matter from the center of the star and Hawking radiation that tends to decrease the mass of the black hole. We study how...... the assumptions for the accretion rate can in fact affect the critical mass beyond which a black hole always grows. We also study to what extent degenerate nuclear matter can impede Hawking radiation due to the fact that emitted particles can be Pauli blocked at the core of the star....

  1. How Artists Overcome Creative Blocks.

    Science.gov (United States)

    Hirst, Barbara

    1992-01-01

    Six practicing artists were interviewed about how they overcome creative blocks. Their responses indicated that feelings of self-doubt, fear, and depression accompany blocks but that relaxing and working on new directions and playing ideas off a supportive person helped to overcome such blocks. (DB)

  2. Block Scheduling in High Schools.

    Science.gov (United States)

    Irmsher, Karen

    1996-01-01

    Block Scheduling has been considered a cure for a lengthy list of educational problems. This report reviews the literature on block schedules and describes some Oregon high schools that have integrated block scheduling. Major disadvantages included resistance to change and requirements that teachers change their teaching strategies. There is…

  3. Abdominal wall blocks in adults

    DEFF Research Database (Denmark)

    Neimann, Jens Dupont Børglum; Gögenür, Ismail; Bendtsen, Thomas F.

    2016-01-01

    Purpose of review Abdominal wall blocks in adults have evolved much during the last decade; that is, particularly with the introduction of ultrasound-guided (USG) blocks. This review highlights recent advances of block techniques within this field and proposes directions for future research.  Rec...

  4. Quilt Block Symmetries

    Science.gov (United States)

    Roscoe, Matt B.; Zephyrs, Joe

    2016-01-01

    Geometric transformations have long been topics of middle school mathematics. Generations of middle school students have learned to reflect, rotate, and translate geometric objects. Historically, though, the mathematics of "movement" might have been considered a departure from other more central middle-grades geometric content areas,…

  5. Characterisation of the ozone sensitivity of Central European plant species: relation to taxonomy, ecology, growth rates and leaf density; Charakterisierung der Ozonsensitivitaet mitteleuropaeischer Pflanzenarten: Beziehung zu Taxonomie, Oekologie, Wachstumsraten und Blattdichte

    Energy Technology Data Exchange (ETDEWEB)

    Franzaring, J.

    2000-07-01

    Fumigation experiments with wild plant species performed in recent years are not necessarily representative for the Central European flora, especially when it comes down to the use of species from red data books in these studies. Moreover, ozone experiments are not representative with respect to plant life forms, taxonomy and ecology. However, first tendencies can be derived: Legumes and Compositae are families comprising many sensitive species with regard to acute injury and growth reductions due to ozone. In contrast to this, the family of Sweet Grasses contains some species with growth stimulations due to ozone. Fastgrowing ruderal strategists and competitive species tend to respond more pronounced than slow-growing species. On the average, plant species with acute injury have thinner leaves than those showing no symptoms. (orig.) [German] Die bislang in Begasungsversuchen untersuchten Wildpflanzenarten repraesentieren nur einen kleinen Teil der mitteleuropaeischen Flora, besonders die Arten der Roten Liste sind noch unterrepraesentiert. Auch hinsichtlich Lebensformen, Taxonomie und Oekologie ist die Ozonwirkungsforschung an Wildpflanzen nur bedingt repraesentativ. Aus den bislang durchgefuehrten Experimenten lassen sich jedoch erste Tendenzen erkennen: Die Familien der Schmetterlings- und Korbblueter enthalten viele ozonsensitive Taxa, was akute Schaeden und Wuchsminderungen anbelangt. In der Familie der Suessgraeser gibt es andererseits Arten, die auf Ozon mit einer Wachstumsstimulierung reagieren. Schnellwuechsige Ruderalstrategen und konkurrenzstarke Arten erweisen sich insgesamt ozonsensitiver als die langsamwuechsigen Arten. Pflanzenarten mit akuter Blattschaedigung haben im Mittel duennere Blaetter als Arten ohne sichtbare Schaeden. (orig.)

  6. Program structure-based blocking

    Science.gov (United States)

    Bertolli, Carlo; Eichenberger, Alexandre E.; O'Brien, John K.; Sura, Zehra N.

    2017-09-26

    Embodiments relate to program structure-based blocking. An aspect includes receiving source code corresponding to a computer program by a compiler of a computer system. Another aspect includes determining a prefetching section in the source code by a marking module of the compiler. Yet another aspect includes performing, by a blocking module of the compiler, blocking of instructions located in the prefetching section into instruction blocks, such that the instruction blocks of the prefetching section only contain instructions that are located in the prefetching section.

  7. Synthesis and Characterization of Stimuli Responsive Block Copolymers, Self-Assembly Behavior and Applications

    Energy Technology Data Exchange (ETDEWEB)

    Determan, Michael Duane [Iowa State Univ., Ames, IA (United States)

    2005-12-17

    The central theme of this thesis work is to develop new block copolymer materials for biomedical applications. While there are many reports of stimuli-responsive amphiphilic [19-21] and crosslinked hydrogel materials [22], the development of an in situ gel forming, pH responsive pentablock copolymer is a novel contribution to the field, Figure 1.1 is a sketch of an ABCBA pentablock copolymer. The A blocks are cationic tertiary amine methacrylates blocked to a central Pluronic F127 triblock copolymer. In addition to the prerequisite synthetic and macromolecular characterization of these new materials, the self-assembled supramolecular structures formed by the pentablock were experimentally evaluated. This synthesis and characterization process serves to elucidate the important structure property relationships of these novel materials, The pH and temperature responsive behavior of the pentablock copolymer were explored especially with consideration towards injectable drug delivery applications. Future synthesis work will focus on enhancing and tuning the cell specific targeting of DNA/pentablock copolymer polyplexes. The specific goals of this research are: (1) Develop a synthetic route for gel forming pentablock block copolymers with pH and temperature sensitive properties. Synthesis of these novel copolymers is accomplished with ATRP, yielding low polydispersity and control of the block copolymer architecture. Well defined macromolecular characteristics are required to tailor the phase behavior of these materials. (2) Characterize relationship between the size and shape of pentablock copolymer micelles and gel structure and the pH and temperature of the copolymer solutions with SAXS, SANS and CryoTEM. (3) Evaluate the temperature and pH induced phase separation and macroscopic self-assembly phenomenon of the pentablock copolymer. (4) Utilize the knowledge gained from first three goals to design and formulate drug delivery formulations based on the multi

  8. Rheological Design of Sustainable Block Copolymers

    Science.gov (United States)

    Mannion, Alexander M.

    Block copolymers are extremely versatile materials that microphase separate to give rise to a rich array of complex behavior, making them the ideal platform for the development of rheologically sophisticated soft matter. In line with growing environmental concerns of conventional plastics from petroleum feedstocks, this work focuses on the rheological design of sustainable block copolymers--those derived from renewable sources and are degradable--based on poly(lactide). Although commercially viable, poly(lactide) has a number of inherent deficiencies that result in a host of challenges that require both creative and practical solutions that are cost-effective and amenable to large-scale production. Specifically, this dissertation looks at applications in which both shear and extensional rheology dictate performance attributes, namely chewing gum, pressure-sensitive adhesives, and polymers for blown film extrusion. Structure-property relationships in the context of block polymer architecture, polymer composition, morphology, and branching are explored in depth. The basic principles and fundamental findings presented in this thesis are applicable to a broader range of substances that incorporate block copolymers for which rheology plays a pivotal role.

  9. Block copolymer investigations

    Science.gov (United States)

    Yufa, Nataliya A.

    The research presented in this thesis deals with various aspects of block copolymers on the nanoscale: their behavior at a range of temperatures, their use as scaffolds, or for creation of chemically striped surfaces, as well as the behavior of metals on block copolymers under the influence of UV light, and the healing behavior of copolymers. Invented around the time of World War II, copolymers have been used for decades due to their macroscopic properties, such as their ability to be molded without vulcanization, and the fact that, unlike rubber, they can be recycled. In recent years, block copolymers (BCPs) have been used for lithography, as scaffolds for nano-objects, to create a magnetic hard drive, as well as in photonic and other applications. In this work we used primarily atomic force microscopy (AFM) and transmission electron microscopy (TEM), described in Chapter II, to conduct our studies. In Chapter III we demonstrate a new and general method for positioning nanoparticles within nanoscale grooves. This technique is suitable for nanodots, nanocrystals, as well as DNA. We use AFM and TEM to demonstrate selective decoration. In Chapters IV and V we use AFM and TEM to study the structure of polymer surfaces coated with metals and self-assembled monolayers. We describe how the surfaces were created, exhibit their structure on the nanoscale, and prove that their macroscopic wetting properties have been altered compared to the original polymer structures. Finally, Chapters VI and VII report out in-situ AFM studies of BCP at high temperatures, made possible only recently with the invention of air-tight high-temperature AFM imaging cells. We locate the transition between disordered films and cylinders during initial ordering. Fluctuations of existing domains leading to domain coarsening are also described, and are shown to be consistent with reptation and curvature minimization. Chapter VII deals with the healing of PS-b-PMMA following AFM-tip lithography or

  10. Celiac ganglia block

    Energy Technology Data Exchange (ETDEWEB)

    Akinci, Devrim [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey); Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey)]. E-mail: oakhan@hacettepe.edu.tr

    2005-09-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation.

  11. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    efficiency of about 15% for commercial Silicon solar cells there is still much to gain. DTU Danchip provides research facilities, equipment and expertise for the building blocks that comprises fabricating the efficient solar cell. In order to get more of the sun light into the device we provide thin film......Photovoltaics (PV), better known as solar cells, are now a common day sight on many rooftops in Denmark.The installed capacity of PV systems worldwide is growing exponentially1 and is the third most importantrenewable energy source today. The cost of PV is decreasing fast with ~10%/year but to make...... it directcompetitive with fossil energy sources a further reduction is needed. By increasing the efficiency of the solar cells one gain an advantage through the whole chain of cost. So that per produced Watt of power less material is spent, installation costs are lower, less area is used etc. With an average...

  12. Atomic Basic Blocks

    Science.gov (United States)

    Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

    Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

  13. Celiac ganglia block

    International Nuclear Information System (INIS)

    Akinci, Devrim; Akhan, Okan

    2005-01-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation

  14. Dimensional reduction for conformal blocks

    Science.gov (United States)

    Hogervorst, Matthijs

    2016-09-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO( d + 1 , 1) up into multiplets of SO( d, 1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d - 1 dimensions. In particular, we obtain a formula for 3 d conformal blocks as an infinite sum over 2 F 1 hypergeometric functions with closed-form coefficients.

  15. Learning Potentials in Number Blocks

    DEFF Research Database (Denmark)

    Majgaard, Gunver; Misfeldt, Morten; Nielsen, Jacob

    2012-01-01

    . The tool is called Number Blocks and it combines physical interaction, learning, and immediate feedback. Number Blocks supports the children's understanding of place value in the sense that it allows them to experiment with creating large numbers. We found the blocks contributed to the learning process...... in several ways. The blocks combined mathematics and play, and they included and supported children at different academic levels. The auditory representation, especially the enhanced rhythmic effects due to using speech synthesis, and the rhythm helped the children to pronounce large numbers. This creates...

  16. Common blocks for ASQS(12

    Directory of Open Access Journals (Sweden)

    Lorenzo Milazzo

    1997-05-01

    Full Text Available An ASQS(v is a particular Steiner system featuring a set of v vertices and two separate families of blocks, B and G, whose elements have a respective cardinality of 4 and 6. It has the property that any three vertices of X belong either to a B-block or to a G-block. The parameter cb is the number of common blocks in two separate ASQSs, both defined on the same set of vertices X . In this paper it is shown that cb ≤ 29 for any pair of ASQSs(12.

  17. 31 CFR 545.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN) SANCTIONS... name of the Taliban or persons whose property or interests in property are blocked pursuant to § 545.201, or in which the Taliban or persons whose property or interests in property are blocked pursuant...

  18. A practical block detector for a depth-encoding PET camera

    International Nuclear Information System (INIS)

    Rogers, J.G.; Moisan, C.; Hoskinson, E.M.; Andreaco, M.S.; Williams, C.W.; Nutt, R.

    1996-01-01

    The depth-of-interaction effect in block detectors degrades the image resolution in commercial PET cameras and impedes the natural evolution of smaller, less expensive cameras. A method for correcting the measured position of each detected gamma ray by measuring its depth-of-interaction was tested and found to recover 38% of the lost resolution at 7.5 cm radius in a tabletop, 50-cm-diameter camera. To obtain the desired depth sensitivity, standard commercial detectors were modified by a simple and practical process that is suitable for mass production of the detectors. The impact of the detector modifications on central image resolution and on the ability of the camera to correct for object scatter were also measured

  19. Synthesis of β-cyclodextrin-Based Star Block Copolymers with Thermo-Responsive Behavior

    Directory of Open Access Journals (Sweden)

    Agnes Wycisk

    2015-05-01

    Full Text Available Star polymers are one example of three-dimensional macromolecules containing several arms with similar molecular weight connected to a central core. Due to their compact structure and their enhanced segment density in comparison to linear polymers of the same molecular weight, they have attracted significant attention during recent years. The preparation of block-arm star copolymers with a permanently hydrophilic block and an “environmentally” sensitive block, which can change its nature from hydrophilic to hydrophobic, leads to nanometer-sized responsive materials with unique properties. These polymers are able to undergo a conformational change or phase transition as a reply to an external stimulus resulting in the formation of core–shell nanoparticles, which further tend to aggregate. Star-shaped copolymers with different cores were synthesized via atom transfer radical polymerization (ATRP. The core-first method chosen as synthetic strategy allows good control over the polymer architecture. First of all the multifunctional initiators were prepared by esterification reaction of the hydroxyl groups with 2-chloropropionyl chloride. Using β-cyclodextrin as core molecules, which possess a well-defined number of functional groups up to 21, allows defining the number of arms per star polymer. In order to prepare stimuli-responsive multi-arm copolymers, containing a stimuli-responsive (poly(N-isopropylacrylamide (PNIPAAm and a non-responsive block (poly(N,N-dimethylacrylamide (PDMAAm, consecutive ATRP was carried out. The polymers were characterized intensively using NMR spectroscopy and size exclusion chromatography (SEC, whereas the temperature-depending aggregation behavior in aqueous solution was determined via turbidimetry and differential scanning calorimetry (DSC.

  20. Sensitivity analysis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  1. Classical Virasoro irregular conformal block

    Science.gov (United States)

    Rim, Chaiho; Zhang, Hong

    2015-07-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  2. Classical Virasoro irregular conformal block

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chaiho; Zhang, Hong [Department of Physics and Center for Quantum Spacetime (CQUeST), Sogang University,Seoul 121-742 (Korea, Republic of)

    2015-07-30

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  3. Four-block beam collimator

    CERN Document Server

    CERN PhotoLab

    1977-01-01

    The photo shows a four-block collimator installed on a control table for positioning the alignment reference marks. Designed for use with the secondary beams, the collimators operated in vacuum conditions. The blocks were made of steel and had a standard length of 1 m. The maximum aperture had a square coss-section of 144 cm2. (See Annual Report 1976.)

  4. OPAL Various Lead Glass Blocks

    CERN Document Server

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  5. Writing Blocks and Tacit Knowledge.

    Science.gov (United States)

    Boice, Robert

    1993-01-01

    A review of the literature on writing block looks at two kinds: inability to write in a timely, fluent fashion, and reluctance by academicians to assist others in writing. Obstacles to fluent writing are outlined, four historical trends in treating blocks are discussed, and implications are examined. (MSE)

  6. Block storage subsystem performance analysis

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    You feel that your service is slow because of the storage subsystem? But there are too many abstraction layers between your software and the raw block device for you to debug all this pile... Let's dive on the platters and check out how the block storage sees your I/Os! We can even figure out what those patterns are meaning.

  7. Mechanical behavior analysis of small-scale modeling of ceramic block masonry structures: geometries effect

    Directory of Open Access Journals (Sweden)

    E. Rizzatti

    Full Text Available This paper presents the experimental results of a research program with ceramic block masonry under compression. Four different block geometries were investigated. Two of them had circular hollows with different net area. The third one had two rectangular hollow and the last block was with rectangular hollows and a double central webs. The prisms and walls were built with two mortar type 1:1:6 (I and 1:0,5:4 (II (proportions by volume of cement: lime: sand. One:three small scale blocks were used to test block, prisms and walls on compression. It was possible to conclude that the block with double central webs gave better results of compressive strength showing to be more efficient. The mortar didn't influenced the compressive strength of prisms and walls.

  8. Fabrics Protect Sensitive Skin from UV Rays

    Science.gov (United States)

    2009-01-01

    Late Johnson Space Center engineer Dr. Robert Dotts headed a team to develop cool suits for children suffering from life-threatening sun sensitivities. Dotts hoped to develop ultraviolet-blocking technology in a fabric that -- unlike in a bulky space suit -- could remain comfortable, light, and breathable in the sun and heat. The team worked with SPF 4 US LLC (SPF) of Madison, Wisconsin to design ultraviolet-blocking cool suits, which protect sun-sensitive patients and enable them to experience life outdoors safely. Using knowledge gained during the NASA collaboration, SPF created an entire line of ultraviolet-blocking apparel.

  9. Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers.

    Science.gov (United States)

    van Genabeek, Bas; Lamers, Brigitte A G; de Waal, Bas F M; van Son, Martin H C; Palmans, Anja R A; Meijer, E W

    2017-10-25

    Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block.

  10. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Student Guide.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This student guide together with an instructor guide comprise a set of curriculum materials on the criminal justice system. The student guide contains self-contained instructional material that students can study at their own pace most of the time. Six major subject areas or blocks, which are further broken down into several units, with some units…

  11. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Instructor Guide.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This instructor guide together with a student guide comprise a set of curriculum materials on the criminal justice system. The instructor guide is a resource for planning and managing individualized, competency-based instruction in six major subject areas or blocks, which are further broken down into several units with some units having several…

  12. ANALYSIS OF CELL BLOCK VS . CONVENTIONAL SMEAR IN FLUID CYTOLOGY

    Directory of Open Access Journals (Sweden)

    Jyotsna

    2015-09-01

    Full Text Available BACKGROUND: The cytological examination of aspirates of serous effusions is a routinely accepted , simple , safe and minimally invasive technique . Diagnosis in this investigation , especially in malignant effusions , helps in staging , prognosis and management of the patients . AIMS: To assess the utility and sensitivity of cell block method over conventional smear technique in cytodiagnosis of the serous effusions . METHODS: A total of 72 fluid specimens were subjected to simultaneous processing by conventional s mear and cell block technique . Each fluid specimen was divided into two equal parts and results compared for cellularity , cell architecture , cytoplasmic and nuclear features . Cell blocks were prepared using modified cell block technique using alcohol forma lin fixative . RESULTS: The utility of cell block technique in diagnosing malignant effusions is highly significant as compared to the conventional smear technique . Also , the technique using alcohol formalin fixative is simple , safe and these chemicals are routinely used in laboratory . CONCLUSION: Cell block technique is superior to conventional smear technique , especially for malignant effusions . It gives more information about the architectural arrangement and the likely source of primary . More important is that diagnostic material in cell blocks is available for special studies for . I mmunohistochemistry which can further supplement our knowledge about the primary source of metastasis

  13. Idiopathic Paroxysmal Atrio-Ventricular Block. What is The Mechanism?

    Science.gov (United States)

    Guerrero-Márquez, Francisco J; Arana-Rueda, Eduardo; Pedrote, Alonso

    2016-01-01

    Idiopathic paroxysmal atrioventricular (AV) block poses a true diagnostic challenge. What is clear about this entity is the confusion about its definition and consequently about its etiology. According to certain sources, the diagnosis of this block requires the lack of a structural cardiac pathology that justifies the observed manifestations and an absence of electrocardiographic disorders prior to an episode. The clinical presentation of idiopathic paroxysmal AV block does not differ from that of another cardiogenic syncope or of a vasovagal syncope with a significant cardioinhibitory component. With respect to the mechanism that explains this block, it has been postulated that patients with low basal adenosine levels exhibit hyperaffinity of the A2 receptors of the AV node. Variations in plasma adenosine levels may favor episodes of paroxysmal AV block. The diagnosis of this block is complex and can require years to determine. Routine electrophysiological examination of these patients is not cost effective due to the low sensitivity and specificity of this approach. Numerous groups have supported the use of an implantable loop recorder to substantiate AV block paroxysms and assess their clinical correlations. Permanent stimulation devices are utilized to reduce syncopal recurrence.

  14. Block by Block: Civic Action in the Battle of Baghdad

    Science.gov (United States)

    2007-11-01

    bedding, and latrine facilities. Additionally, provide milk , baby formula, diapers, 7 Bogart: Block by Block and infant/family care items such as...viable agricultural businesses. The cattle are a cross breed of a “regular” Iraqi cow and a water buffalo. Chicken farms are mostly egg farms, and...a problem. Contractors did not want to work for fear of being shot or kid - napped. For example, four contractors were shot over the duration of

  15. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [DESY Hamburg, Theory Group,Notkestraße 85, 22607 Hamburg (Germany); Sobko, Evgeny [Nordita and Stockholm University,Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden); Isachenkov, Mikhail [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel)

    2017-03-15

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  16. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Sobko, Evgeny [Stockholm Univ. (Sweden); Nordita, Stockholm (Sweden); Isachenkov, Mikhail [Weizmann Institute of Science, Rehovoth (Israel). Dept. of Particle Physics and Astrophysics

    2016-12-07

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  17. European temperature responses to blocking and ridge regional patterns

    Science.gov (United States)

    Sousa, Pedro M.; Trigo, Ricardo M.; Barriopedro, David; Soares, Pedro M. M.; Santos, João A.

    2018-01-01

    Blocking occurrence and its impacts on European temperature have been studied in the last decade. However, most previous studies on blocking impacts have focused on winter only, disregarding its fingerprint in summer and differences with other synoptic patterns that also trigger temperature extremes. In this work, we provide a clear distinction between high-latitude blocking and sub-tropical ridges occurring in three sectors of the Euro-Atlantic region, describing their climatology and consequent impacts on European temperature during both winter and summer. Winter blocks (ridges) are generally associated to colder (warmer) than average conditions over large regions of Europe, in some areas with anomalies larger than 5 °C, particularly for the patterns occurring in the Atlantic and Central European sectors. During summer, there is a more regional response characterized by above average temperature for both blocking and ridge patterns, especially those occurring in continental areas, although negative temperature anomalies persist in southernmost areas during blocking. An objective analysis of the different forcing mechanisms associated to each considered weather regime has been performed, quantifying the importance of the following processes in causing the temperature anomalies: horizontal advection, vertical advection and diabatic heating. While during winter advection processes tend to be more relevant to explain temperature responses, in summer radiative heating under enhanced insolation plays a crucial role for both blocking and ridges. Finally, the changes in the distributions of seasonal temperature and in the frequencies of extreme temperature indices were also examined for specific areas of Europe. Winter blocking and ridge patterns are key drivers in the occurrence of regional cold and warm extreme temperatures, respectively. In summer, they are associated with substantial changes in the frequency of extremely warm days, but with different signatures in

  18. Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical Illness: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Price, David R; Mikkelsen, Mark E; Umscheid, Craig A; Armstrong, Ehrin J

    2016-11-01

    The relationship between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness remains unclear. We examined the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, and critical illness myopathy. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of included studies were searched from database inception until September 24, 2015. Randomized controlled trials and prospective observational studies examining the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, or critical illness myopathy. One author screened titles/abstracts. Two authors independently reviewed full text and extracted data from included studies. Meta-analysis was performed using the DerSimonian-Laird random effects model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel plots and heterogeneity with the I statistic. Of 2,170 titles/abstracts screened, 99 full texts were selected for review, yielding one randomized controlled trial and 18 prospective observational studies, for a total of 2,254 patients. The randomized controlled trial did not show an association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness (odds ratio, 1.21; 95% CI, 0.67-2.19), but pooled data from all included studies suggested a modest association (odds ratio, 1.25; 95% CI, 1.06-1.48; I = 16%). Funnel plots suggested reporting bias, and sensitivity analyses showed a disproportionate contribution from critical illness polyneuropathy/critical illness myopathy and severe sepsis/septic shock studies. This meta-analysis suggests a modest association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness; limitations include studies with a high risk of bias and a

  19. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter

    2013-01-01

    The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

  20. The wild tapered block bootstrap

    DEFF Research Database (Denmark)

    Hounyo, Ulrich

    -based method in terms of asymptotic accuracy of variance estimation and distribution approximation. For stationary time series, the asymptotic validity, and the favorable bias properties of the new bootstrap method are shown in two important cases: smooth functions of means, and M-estimators. The first......-order asymptotic validity of the tapered block bootstrap as well as the wild tapered block bootstrap approximation to the actual distribution of the sample mean is also established when data are assumed to satisfy a near epoch dependent condition. The consistency of the bootstrap variance estimator for the sample......In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block...

  1. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2016-09-12

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  2. Defying gravity using Jenga™ blocks

    Science.gov (United States)

    Tan, Yin-Soo; Yap, Kueh-Chin

    2007-11-01

    This paper describes how Jenga™ blocks can be used to demonstrate the physics of an overhanging tower that appears to defy gravity. We also propose ideas for how this demonstration can be adapted for the A-level physics curriculum.

  3. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine.

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H; Johnson, Kirk W

    2017-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene-related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene-related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

  4. Techno-economic analysis of supercritical carbon dioxide power blocks

    Science.gov (United States)

    Meybodi, Mehdi Aghaei; Beath, Andrew; Gwynn-Jones, Stephen; Veeraragavan, Anand; Gurgenci, Hal; Hooman, Kamel

    2017-06-01

    Developing highly efficient power blocks holds the key to enhancing the cost competitiveness of Concentration Solar Thermal (CST) technologies. Supercritical CO2 (sCO2) Brayton cycles have proved promising in providing equivalent or higher cycle efficiency than supercritical or superheated steam cycles at temperatures and scales relevant for Australian CST applications. In this study, a techno-economic methodology is developed using a stochastic approach to determine the ranges for the cost and performance of different components of central receiver power plants utilizing sCO2 power blocks that are necessary to meet the Australian Solar Thermal Initiative (ASTRI) final LCOE target of 12 c/kWh.

  5. Allergic sensitization

    DEFF Research Database (Denmark)

    van Ree, Ronald; Hummelshøj, Lone; Plantinga, Maud

    2014-01-01

    Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased pe...

  6. A discrete element modelling approach for block impacts on trees

    Science.gov (United States)

    Toe, David; Bourrier, Franck; Olmedo, Ignatio; Berger, Frederic

    2015-04-01

    These past few year rockfall models explicitly accounting for block shape, especially those using the Discrete Element Method (DEM), have shown a good ability to predict rockfall trajectories. Integrating forest effects into those models still remain challenging. This study aims at using a DEM approach to model impacts of blocks on trees and identify the key parameters controlling the block kinematics after the impact on a tree. A DEM impact model of a block on a tree was developed and validated using laboratory experiments. Then, key parameters were assessed using a global sensitivity analyse. Modelling the impact of a block on a tree using DEM allows taking into account large displacements, material non-linearities and contacts between the block and the tree. Tree stems are represented by flexible cylinders model as plastic beams sustaining normal, shearing, bending, and twisting loading. Root soil interactions are modelled using a rotation stiffness acting on the bending moment at the bottom of the tree and a limit bending moment to account for tree overturning. The crown is taken into account using an additional mass distribute uniformly on the upper part of the tree. The block is represented by a sphere. The contact model between the block and the stem consists of an elastic frictional model. The DEM model was validated using laboratory impact tests carried out on 41 fresh beech (Fagus Sylvatica) stems. Each stem was 1,3 m long with a diameter between 3 to 7 cm. Wood stems were clamped on a rigid structure and impacted by a 149 kg charpy pendulum. Finally an intensive simulation campaign of blocks impacting trees was done to identify the input parameters controlling the block kinematics after the impact on a tree. 20 input parameters were considered in the DEM simulation model : 12 parameters were related to the tree and 8 parameters to the block. The results highlight that the impact velocity, the stem diameter, and the block volume are the three input

  7. Analysis of Separated Flow over Blocked Surface

    Directory of Open Access Journals (Sweden)

    Onur YEMENİCİ

    2013-04-01

    Full Text Available In this study, the separated flow over flat and blocked surfaces was investigated experimentally. Velocity and turbulence intensity measurements were carried out by a constanttemperature hot wire anemometer and static pressure measurements by a micro-manometer. The flow separations and reattachments were occurred before the first block, on the first block, between blocks and after the last block, and the presence of the blocks significantly increased the turbulent intensity

  8. Reforming residential electricity tariff in China: Block tariffs pricing approach

    International Nuclear Information System (INIS)

    Sun, Chuanwang; Lin, Boqiang

    2013-01-01

    The Chinese households that make up approximately a quarter of world households are facing a residential power tariff reform in which a rising block tariff structure will be implemented, and this tariff mechanism is widely used around the world. The basic principle of the structure is to assign a higher price for higher income consumers with low price elasticity of power demand. To capture the non-linear effects of price and income on elasticities, we set up a translog demand model. The empirical findings indicate that the higher income consumers are less sensitive than those with lower income to price changes. We further put forward three proposals of Chinese residential electricity tariffs. Compared to a flat tariff, the reasonable block tariff structure generates more efficient allocation of cross-subsidies, better incentives for raising the efficiency of electricity usage and reducing emissions from power generation, which also supports the living standards of low income households. - Highlights: • We design a rising block tariff structure of residential electricity in China. • We set up a translog demand model to find the non-linear effects on elasticities. • The higher income groups are less sensitive to price changes. • Block tariff structure generates more efficient allocation of cross-subsidies. • Block tariff structure supports the living standards of low income households

  9. Secure Block Ciphers - Cryptanalysis and Design

    DEFF Research Database (Denmark)

    Tiessen, Tyge

    The rapid evolution of computational devices and the widespread adoption of digital communication have deeply transformed the way we conduct both business and everyday life and they continue to do so. The ability to ensure confidentiality and integrity of information sent over digital channels...... is fundamental to this development and is absolutely essential for all private and corporate communication, ranging from bank transactions, digital citizen services, and remote computer access, to cell phone calls and instant messaging. The vast majority of secured data sent over all types of networks...... is encrypted using so-called symmetric ciphers. The security of our digital infrastructure thus rests at its very base on their security. The central topic of this thesis is the security of block ciphers – the most prominent form of symmetric ciphers. This thesis is separated in two parts. The first part...

  10. Climate Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lindzen, Richard [M.I.T.

    2011-11-09

    Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

  11. Aqueous self-assembly of a protein-mimetic ampholytic block copolypeptide

    Czech Academy of Sciences Publication Activity Database

    Sun, J.; Černoch, Peter; Völkel, A.; Wei, Y.; Ruokolainen, J.; Schlaad, H.

    2016-01-01

    Roč. 49, č. 15 (2016), s. 5494-5501 ISSN 0024-9297 Institutional support: RVO:61389013 Keywords : block copolymers * pH sensitive * vesicles Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.835, year: 2016

  12. Neuroanatomical substrate of noise sensitivity

    DEFF Research Database (Denmark)

    Kliuchko, Marina; Puoliväli, Tuomas; Heinonen-Guzejev, Marja

    2018-01-01

    Recent functional studies suggest that noise sensitivity, a trait describing attitudes towards noise and predicting noise annoyance, is associated with altered processing in the central auditory system. In the present work, we examined whether noise sensitivity could be related to the structural...... and hippocampus was measured as well. According to our findings, noise sensitivity is associated with the grey matter volume in the selected structures. Among those, we propose and discuss particular areas, previously linked to auditory perceptual, emotional and interoceptive processing, in which larger grey...... matter volume seems to be related to higher noise sensitivity....

  13. Gluten Sensitivity

    Science.gov (United States)

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  14. Radioecological sensitivity

    International Nuclear Information System (INIS)

    Howard, Brenda J.; Strand, Per; Assimakopoulos, Panayotis

    2003-01-01

    After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

  15. Radial Coordinates for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2013-01-01

    We develop the theory of conformal blocks in CFT_d expressing them as power series with Gegenbauer polynomial coefficients. Such series have a clear physical meaning when the conformal block is analyzed in radial quantization: individual terms describe contributions of descendants of a given spin. Convergence of these series can be optimized by a judicious choice of the radial quantization origin. We argue that the best choice is to insert the operators symmetrically. We analyze in detail the resulting "rho-series" and show that it converges much more rapidly than for the commonly used variable z. We discuss how these conformal block representations can be used in the conformal bootstrap. In particular, we use them to derive analytically some bootstrap bounds whose existence was previously found numerically.

  16. Diversity Gain through Antenna Blocking

    Directory of Open Access Journals (Sweden)

    V. Dehghanian

    2012-01-01

    Full Text Available As part of the typical usage mode, interaction between a handheld receiver antenna and the operator's RF absorbing body and nearby objects is known to generate variability in antenna radiation characteristics through blocking and pattern changes. It is counterintuitive that random variations in blocking can result in diversity gain of practical applicability. This diversity gain is quantified from a theoretical and experimental perspective. Measurements carried out at 1947.5 MHz verify the theoretical predictions, and a diversity gain of 3.1 dB was measured through antenna blocking and based on the utilized measurement setup. The diversity gain can be exploited to enhance signal detectability of handheld receivers based on a single antenna in indoor multipath environments.

  17. Cryptanalysis of Selected Block Ciphers

    DEFF Research Database (Denmark)

    Alkhzaimi, Hoda A.

    , pseudorandom number generators, and authenticated encryption designs. For this reason a multitude of initiatives over the years has been established to provide a secure and sound designs for block ciphers as in the calls for Data Encryption Standard (DES) and Advanced Encryption Standard (AES), lightweight...... ciphers initiatives, and the Competition for Authenticated Encryption: Security, Applicability, and Robustness (CAESAR). In this thesis, we first present cryptanalytic results on different ciphers. We propose attack named the Invariant Subspace Attack. It is utilized to break the full block cipher...... on the family of lightweight block cipher SIMON that was published by the U.S National Security Agency (NSA). The ciphers are developed with optimization towards both hardware and software in mind. While the specification paper discusses design requirements and performance of the presented lightweight ciphers...

  18. Climatological features of blocking anticyclones

    International Nuclear Information System (INIS)

    Lupo, A.R.; Smith, P.J.; Oglesby, R.J.

    1994-01-01

    Several climatological studies have been previously performed using large observational data sets (i.e., 10 years or longer) in order to determine the predominant characteristics of blocking anticyclones, including favored development regions, duration, preferred seasonal occurrence, and frequency of occurrence. These studies have shown that blocking anticyclones occur most frequently from October to April over the eastern Atlantic and Pacific oceans downstream from both the North American and Asian continental regions and the storm track regions to the east of these continents. Some studies have also revealed the presence of a third region block formation in western Russia near 40 degrees E which is associated with another storm track region over the Mediterranean and western Asia

  19. Projectors, shadows, and conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Simmons-Duffin, David [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States)

    2014-04-24

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism' of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d-dimensions can be expressed as integrals over the projective null-cone in the “embedding space' ℝ{sup d+1,1}. Taking care with their analytic structure, these integrals can be evaluated in great generality, reducing the computation of conformal blocks to a bookkeeping exercise. To facilitate calculations in four-dimensional CFTs, we introduce techniques for writing down conformally-invariant correlators using auxiliary twistor variables, and demonstrate their use in some simple examples.

  20. Projectors, Shadows, and Conformal Blocks

    OpenAIRE

    Simmons-Duffin, David

    2012-01-01

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism” of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d -dimensions can be expressed as integrals over the projective null-cone in the “embedding space” $ \\mathbb{R} $ d +1,1 . Taking ...

  1. THE SIGNIFICANCE OF PATTERN ERG IN CENTRAL VEIN OCCLUSION

    Directory of Open Access Journals (Sweden)

    Saša Novak

    2004-12-01

    Full Text Available Pattern electroretinogram (PERG findings were analysed in 30 patients with central retinal vein occlusion. Latency and amplitude values of PERG waves were compared with the results obtained in 30 healthy individuals after sample randomisation. In 15 cases with „hemorrhagic type” occlusion of the central retinal vein significantly reduced N1-P1 wave amplitude was noted (0,369 mV, related to „exudative“ disease type (0,557 mV, as well as to the control group of examines (0,782 mV. PERG was described as the sensitive method and important indicator in damage assessment, ie. ischemia in the ganglional cell layer in central retinal vein occlusion. Ischemia increases anoxia, which influences not only the axons but also the enzymatic and transport processes within the cell bodies, dendrites, axons and axonal terminals. Slowing down of the fast phase of axoplasmatic transport in the axons in ischemic damage blocked transmission impulses which could be evident through different degrees of PERG wave amplitude reduction. With this method the patients can be selected in whom due to severe retinal ischemia there is the risk of neovascular glaucomma and maculopathy, which is the absolute indication for panlaser-photocoagulation.

  2. Central Solenoid

    CERN Multimedia

    2002-01-01

    The Central Solenoid (CS) is a single layer coil wound internally in a supporting cylinder housed in the cryostat of the Liquid Argon Calorimeter. It was successfully tested at Toshiba in December 2000 and was delivered to CERN in September 2001 ready for integration in the LAr Calorimeter in 2003. An intermediate test of the chimney and proximity cryogenics was successfully performed in June 2002.

  3. Main-chain supramolecular block copolymers.

    Science.gov (United States)

    Yang, Si Kyung; Ambade, Ashootosh V; Weck, Marcus

    2011-01-01

    Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.

  4. Building Blocks for Personal Brands

    Science.gov (United States)

    Thomas, Lisa Carlucci

    2011-01-01

    In this article, the author discusses the four essential building blocks for personal brands: (1) name; (2) message; (3) channels; and (4) bridges. However, outstanding building materials can only take a person so far. The author emphasizes that vision, determination, faith, a sense of humor, and humility are also required.

  5. Control rod removal blocking device

    International Nuclear Information System (INIS)

    Yoshioka, Ritsuo.

    1981-01-01

    Purpose: To prevent excess power increase resulted from erroneous control rod removal during high power operation in BWR type reactor by decreasing the continuous removal enabling distance for the control rods along with increase in the reactor power where the reactor power is greater than a predetermined level. Constitution: When control rod selection signals are supplied from a control unit to a control rod removal blocking device, the blocking device judges whether the reactor core power is greater than a predetermined value A or not, using reactor core power signals outputted from an average power monitor. Where the reactor core power exceeds the predetermined value A and if the reactor core power is relatively low, a large continuous removal enabling distance N 1 is calculated in the blocking device to allow the continuous removal as far as the notch N 1 . The continuous removal enabling distance is shortened as the reactor core power increases and the removal is blocked, for example, at notch N 2 . While on the other hand, if the reactor core power is below the predetermined value A, both of the notchwise removal and the continuous removal are enabled. (Seki, T.)

  6. First Degree Pacemaker Exit Block

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2016-10-01

    Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

  7. Vagal Blocking for Obesity Control

    DEFF Research Database (Denmark)

    Johannessen, Helene; Revesz, David; Kodama, Yosuke

    2017-01-01

    BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device...

  8. Thermo-responsive block copolymers

    NARCIS (Netherlands)

    Mocan Cetintas, Merve

    2017-01-01

    Block copolymers (BCPs) are remarkable materials because of their self-assembly behavior into nano-sized regular structures and high tunable properties. BCPs are in used various applications such as surfactants, nanolithography, biomedicine and nanoporous membranes. In these thesis, we aimed to

  9. Scintigraphic visualization of 'Blocking' thyroid

    International Nuclear Information System (INIS)

    Simeonova, A.; Kostadinova, I.

    2006-01-01

    Full text: An important problem in nuclear endocrinology is 'blocking' of thyroid gland, which necessitates postpone of the investigation, adverse clinical effect of stopping medications and a delay of making diagnosis. The aim of the study was to introduce and to determine the clinical value of the scintigraphy with 99mTc-MIBI in patients (Pts) with 'blocked thyroid'. In 365 Pts (aged 38-75 years), indicated for a thyroid scintigraphy after proper preparation, an investigation was performed with 74 MBq 99mTc-pertechnetate, 20 min. p.i. In 14 of them (3.8%), the thyroid was 'blocked' and additional scintigraphy was done with 370-555 MBq 99mTc-MIBI, 15 and 120 min.p.i. It was estimated that in all Pts there was a visualization of thyroid. In 1 of them, a large 'hot' nodule was visualized in the early and late image. Later on a differentiated thyroid carcinoma was proved histologically. In the rest of the patients 'cold' nodules with different size were visualized, eventually as a result of cysts. As a conclusion we consider, that a scintigraphy with 99mTc-MIBI is a useful tool in Pts with 'blocked' thyroid. In addition an evaluation of the thyroid nodule could be done and therefore- a recommendation for therapy

  10. Evaluation of Suitability of Non-Standardized Test Block for Ultrasonic Testing

    International Nuclear Information System (INIS)

    Kwon, Ho Young; Lim, Jong Ho; Kang, Sei Sun

    2000-01-01

    Standard Test Block(STB) for UT(Ultrasonic Testing) is a block approved by authoritative for material, shape and quality. STB is used for characteristic tests, sensitivity calibration and control of the time base range of UT inspection devices. The material, size and chemical components of STB should be strictly controlled to meet the related standards such as ASTM and JIS because it has an effect upon sensitivity, resolution and reproductivity of UT. The STBs which are not approved are sometimes used because the qualified STBs are very expensive. So, the purpose of this study is to survey the characteristics, quality and usability of Non-Standardized Test Blocks. Non-Standardized Test Blocks did not meet the standard requirements in size or chemical components, and ultrasonic characteristics. Therefore if the Non-Standardized Test Blocks are used without being tested, it's likely to cause errors in detecting the location and measuring the size of the defects

  11. [Distal sciatic nerve blocks: randomized comparison of nerve stimulation and ultrasound guided intraepineural block].

    Science.gov (United States)

    Seidel, R; Natge, U; Schulz, J

    2013-03-01

    The design of this study is related to an important current issue: should local anesthetics be intentionally injected into peripheral nerves? Answering this question is not possible without better knowledge regarding classical methods of nerve localization (e.g. cause of paresthesias and nerve stimulation technique). Have intraneural injections ever been avoided? This prospective, randomized comparison of distal sciatic nerve block with ultrasound guidance tested the hypothesis that intraneural injection of local anesthetics using the nerve stimulation technique is common and associated with a higher success rate. In this study 250 adult patients were randomly allocated either to the nerve stimulation group (group NS, n = 125) or to the ultrasound guidance group (group US, n = 125). The sciatic nerve was anesthetized with 20 ml prilocaine 1% and 10 ml ropivacaine 0.75%. In the US group the goal was an intraepineural needle position. In the NS group progress of the block was observed by a second physician using ultrasound imaging but blinded for the investigator performing the nerve stimulation. The main outcome variables were time until readiness for surgery (performance time and onset time), success rate and frequency of paresthesias. In the NS group needle positions and corresponding stimulation thresholds were recorded. In both groups seven patients were excluded from further analysis because of protocol violation. In the NS group (n = 118) the following needle positions were estimated: intraepineural (NS 1, n = 51), extraparaneural (NS 2, n = 33), needle tip dislocation from intraepineural to extraparaneural while injecting local anesthetic (NS 3, n = 19) and other or not determined needle positions (n = 15). Paresthesias indicated an intraneural needle position with an odds ratio of 27.4 (specificity 98.8%, sensitivity 45.9%). The success rate without supplementation was significantly higher in the US group (94.9% vs. 61.9%, p blocks

  12. Blocking blue light during mania - markedly increased regularity of sleep and rapid improvement of symptoms: a case report.

    Science.gov (United States)

    Henriksen, Tone E G; Skrede, Silje; Fasmer, Ole Bernt; Hamre, Børge; Grønli, Janne; Lund, Anders

    2014-12-01

    Available pharmacological treatment of mania is insufficient. Virtual darkness therapy (blue light-blocking treatment by means of orange-tinted glasses) is a promising new treatment option for mania. The basis for this might be the recently identified blue light-sensitive retinal photoreceptor, which is solely responsible for light stimulus to the circadian master clock. This is the first case report describing the clinical course of a closely monitored, hospitalized patient in a manic episode first receiving clear-lensed, and then blue light-blocking glasses. A 58-year-old Caucasian man, with bipolar I disorder and three previous manic episodes, was hospitalized during a manic episode. In addition to pharmacological treatment, he was treated with clear-lensed glasses for seven days, then one day without glasses, followed by six days of blue light-blocking glasses. During the entire observational period, he wore an actigraph with internal light sensors. Manic symptoms were unaltered during the first seven days. The transition to the blue-blocking regime was followed by a rapid and sustained decline in manic symptoms accompanied by a reduction in total sleep, a reduction in motor activity during sleep intervals, and markedly increased regularity of sleep intervals. The patient's total length of hospital stay was 20 days shorter than the average time during his previous manic episodes. The unusually rapid decline in symptoms, accompanied by uniform sleep parameter changes toward markedly increased regularity, suggest that blue-blockers might be targeting a central mechanism in the pathophysiology of mania that needs to be explored both in clinical research and in basic science. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Central sleep apnea

    Science.gov (United States)

    Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... Central sleep apnea results when the brain temporarily stops sending signals to the muscles that control breathing. The condition ...

  14. MYOCARDIAL DEFORMATION AND COMPLETE LEFT BUNDLE BRANCH BLOCK

    Directory of Open Access Journals (Sweden)

    E. N. Pavlyukova

    2015-12-01

    Full Text Available Tissue Doppler imaging is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular systolic and diastolic function. Over the last 10 years, myocardial deformation imaging has become possible initially with tissue Doppler , and more recently with myocardial speckle-tracking using 2D echocardiography. Unlike simple tissue velocity measurements, deformation measurements are specific for the region of interest. Strain rate or strain measurements have been used as sensitive indicators for subclinical diseases, and it is the most widely used tool to assess mechanical dyssynchrony. Left bundle branch block is a frequent, etiologically heterogeneous, clinically hostile and diagnostically challenging entity. About 2% of patients underwent cardiac stress testing show stable or intermittent left bundle branch block. Presence of left bundle branch block is associated with a lower and slower diastolic coronary flow velocity especially during hyperemia. Stress echocardiography is the best option for the diagnosis of ischemic heart disease, albeit specificity and sensitivity reduce in patients with left bundle branch block in the territory of left anterior descending artery in presence of initial septum dyskinesia.

  15. 31 CFR 585.216 - Expenses of maintaining blocked property; liquidation into blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation into blocked account. 585.216 Section 585.216 Money and Finance: Treasury Regulations... blocked property; liquidation into blocked account. (a) Except as otherwise authorized, and... expenses incident to the blocking and maintenance of property blocked pursuant to § 585.201 or § 585.215(a...

  16. On the Eigenvalues and Eigenvectors of Block Triangular Preconditioned Block Matrices

    KAUST Repository

    Pestana, Jennifer

    2014-01-01

    Block lower triangular matrices and block upper triangular matrices are popular preconditioners for 2×2 block matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned matrices are related. © 2014 Society for Industrial and Applied Mathematics.

  17. Sensitivity of film measured off-axis ratios to film calibration curve using radiochromic film; Sensibilidade das razoes fora do eixo central medidas para a curva de calibracao de filmes usando filme radiocromico

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Hernandez, Diana [Universidad Nacional Autnoma de Mexico (UNAM), Mexico City (Mexico). Inst. de Fisica; Larraga-Gutierrez, Jose M. [Instituto Nacional de Neurologia y Neurocirugia, Mexico City (Mexico). Unidad de Radioneurocirugia. Lab. de Fisica Medica

    2011-07-01

    Off-axis ratios of conical beams generated with a stereotactic radiosurgery-dedicated Linac were measured with EBT2 film and stereotactic diode. The sensitivity of both full width at half maximum (FWHM) and penumbras (80-20% and 90-10%, respectively), with respect to the characteristics of the film calibration curve fit, was investigated. In all cases, penumbras resulted to be more sensitive than FWHM. However, these differences were, in general, smaller than the ones found between EBT2 reference values and the stereotactic diode measurements. The larger variation in OAR parameters was found to depend on whether the fit intersected or not the origin. A 1D gamma-index analysis showed this difference can be important in all measured conical beams. (author)

  18. Reduced climate sensitivity of carbon, oxygen and hydrogen stable isotope ratios in tree-ring cellulose of silver fir (Abies alba Mill.) influenced by background SO2 in Franconia (Germany, Central Europe).

    Science.gov (United States)

    Boettger, Tatjana; Haupt, Marika; Friedrich, Michael; Waterhouse, John S

    2014-02-01

    The climate sensitivity of carbon (δ(13)C), oxygen (δ(18)O) and hydrogen (δ(2)H) isotope signatures in tree-ring cellulose of Abies alba Mill. from a marginally industrialized area of Franconia (Germany) was analysed for the last 130 years. All isotopes preserve climatic signals up to c. 1950 AD. After 1950 we observe a clear reduction in climate sensitivity of δ(13)C and δ(2)H while δ(18)O - climate relations remain well pronounced. Nevertheless statistical tests implied that SO2 background emissions of West Germany had influenced isotope signatures long before 1950. The relationships between isotope values and concentrations of SO2, dust, O3 and NO2 at the regional level during the period 1979-2006 indicate that δ(13)C and δ(18)O were influenced primarily by SO2. The impact of SO2 on δ(2)H was negligible, but the observed reduction of climate sensitivity may be caused by synergic influences. The results have significant implications if isotope signatures from tree-rings from anthropogenic influenced regions are used to reconstruct past climate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Block-Matching Based Multifocus Image Fusion

    Directory of Open Access Journals (Sweden)

    Feng Zhu

    2015-01-01

    Full Text Available A new multifocus image fusion method is proposed. Two image blocks are selected by sliding the window from the two source images at the same position, discrete cosine transform (DCT is implemented, respectively, on these two blocks, and the alternating component (AC energy of these blocks is then calculated to decide which is the well-focused one. In addition, block matching is used to determine a group of image blocks that are all similar to the well-focused reference block. Finally, all the blocks are returned to their original positions through weighted average. The weight is decided with the AC energy of the well-focused block. Experimental results demonstrate that, unlike other spatial methods, the proposed method effectively avoids block artifacts. The proposed method also significantly improves the objective evaluation results, which are obtained by some transform domain methods.

  20. Blocking incidental frustration during bargaining.

    Science.gov (United States)

    Vargas, Maria Esperanza S; Brown, Anna-Leigh; Durkee, Cassandra M; Sim, Hoeun

    2018-02-08

    The current study examined the effects of an intervention aimed at blocking the transfer of frustration from a previous experience (i.e. recall task) to a subsequent and unrelated task (i.e. ultimatum bargaining task). Participants who went through the intervention were more likely to accept unfair offers in the ultimatum bargaining task than those who did not go through the intervention. These results show that participants who were blocked from transferring their feelings of frustration from the recall task to the subsequent bargaining task (no-transfer condition) more likely accepted unfair offers than those who inadvertently transferred their feelings of frustration (transfer condition). The effect of conditions on accept-reject decisions in the ultimatum bargaining was mediated by reported feelings of frustration.

  1. Blocking layer modeling for temperature analysis of electron transfer ...

    African Journals Online (AJOL)

    In this article, we simulate thermal effects on the electron transfer rate from three quantum dots CdSe, CdS and CdTe to three metal oxides TiO2, SnO2 and ZnO2 in the presence of four blocking layers ZnS, ZnO, TiO2 and Al2O3, in a porous quantum dot sensitized solar cell (QDSSC) structure, using Marcus theory.

  2. UAV PHOTOGRAMMETRY: BLOCK TRIANGULATION COMPARISONS

    Directory of Open Access Journals (Sweden)

    R. Gini

    2013-08-01

    Full Text Available UAVs systems represent a flexible technology able to collect a big amount of high resolution information, both for metric and interpretation uses. In the frame of experimental tests carried out at Dept. ICA of Politecnico di Milano to validate vector-sensor systems and to assess metric accuracies of images acquired by UAVs, a block of photos taken by a fixed wing system is triangulated with several software. The test field is a rural area included in an Italian Park ("Parco Adda Nord", useful to study flight and imagery performances on buildings, roads, cultivated and uncultivated vegetation. The UAV SenseFly, equipped with a camera Canon Ixus 220HS, flew autonomously over the area at a height of 130 m yielding a block of 49 images divided in 5 strips. Sixteen pre-signalized Ground Control Points, surveyed in the area through GPS (NRTK survey, allowed the referencing of the block and accuracy analyses. Approximate values for exterior orientation parameters (positions and attitudes were recorded by the flight control system. The block was processed with several software: Erdas-LPS, EyeDEA (Univ. of Parma, Agisoft Photoscan, Pix4UAV, in assisted or automatic way. Results comparisons are given in terms of differences among digital surface models, differences in orientation parameters and accuracies, when available. Moreover, image and ground point coordinates obtained by the various software were independently used as initial values in a comparative adjustment made by scientific in-house software, which can apply constraints to evaluate the effectiveness of different methods of point extraction and accuracies on ground check points.

  3. [THE TECHNOLOGY "CELL BLOCK" IN CYTOLOGICAL PRACTICE].

    Science.gov (United States)

    Volchenko, N N; Borisova, O V; Baranova, I B

    2015-08-01

    The article presents summary information concerning application of "cell block" technology in cytological practice. The possibilities of implementation of various modern techniques (immune cytochemnical analysis. FISH, CISH, polymerase chain reaction) with application of "cell block" method are demonstrated. The original results of study of "cell block" technology made with gelatin, AgarCyto and Shadon Cyoblock set are presented. The diagnostic effectiveness of "cell block" technology and common cytological smear and also immune cytochemical analysis on samples of "cell block" technology and fluid cytology were compared. Actually application of "cell block" technology is necessary for ensuring preservation of cell elements for subsequent immune cytochemical and molecular genetic analysis.

  4. Block Fusion on Dynamically Adaptive Spacetree Grids for Shallow Water Waves

    KAUST Repository

    Weinzierl, Tobias

    2014-09-01

    © 2014 World Scientific Publishing Company. Spacetrees are a popular formalism to describe dynamically adaptive Cartesian grids. Even though they directly yield a mesh, it is often computationally reasonable to embed regular Cartesian blocks into their leaves. This promotes stencils working on homogeneous data chunks. The choice of a proper block size is sensitive. While large block sizes foster loop parallelism and vectorisation, they restrict the adaptivity\\'s granularity and hence increase the memory footprint and lower the numerical accuracy per byte. In the present paper, we therefore use a multiscale spacetree-block coupling admitting blocks on all spacetree nodes. We propose to find sets of blocks on the finest scale throughout the simulation and to replace them by fused big blocks. Such a replacement strategy can pick up hardware characteristics, i.e. which block size yields the highest throughput, while the dynamic adaptivity of the fine grid mesh is not constrained - applications can work with fine granular blocks. We study the fusion with a state-of-the-art shallow water solver at hands of an Intel Sandy Bridge and a Xeon Phi processor where we anticipate their reaction to selected block optimisation and vectorisation.

  5. Facile synthesis of main-chain degradable block copolymers for performance enhanced dismantlable adhesion.

    Science.gov (United States)

    Sato, Eriko; Hagihara, Takashi; Matsumoto, Akikazu

    2012-04-01

    Block copolymers consisting of readily degradable polyperoxides and non-degradable vinyl polymers as the block segments were successfully synthesized by reversible chain transfer catalyzed polymerization, which is one of living radical polymerization techniques. The block copolymers showed characteristic morphology and wettability being different from the polymer blends. When block copolymers containing polyperoxide and polymethacrylate blocks were heated below 150 °C, the polyperoxide blocks were completely degraded and the polymethacrylate blocks were recovered without degradation. Block copolymers containing a poly(2-ethylhexyl methacrylate) block were then investigated as a dismantlable adhesion material, which requires adequate bonding strength during use and easy debonding on demand. Among the several block copolymers, the one consisting of poly(2-ethylhexyl methacrylate) and polyperoxide from methyl sorbate (PPMS) (M(n) = 4900) exhibited good performance as a pressure-sensitive adhesive (PSA). After heating the test specimens in a temperature range from 60 to 100 °C, PSA performance, which was evaluated by 180° peel strength and shear holding power measurements, was significantly diminished. Especially, after heating at 100 °C for 1 h, spontaneous debonding of some test specimens was observed because of the evolution of volatile acetaldehyde from PPMS.

  6. Pampia: A large cratonic block missing in the Rodinia supercontinent

    Science.gov (United States)

    Ramos, Victor A.; Vujovich, Graciela; Martino, Roberto; Otamendi, Juan

    2010-09-01

    The large cratonic block of Pampia, at present in southern South America, is commonly missing in recent comprehensive reconstructions of Rodinia. This block was the conjugate margin of the Amazonia craton that corresponds to the W-NW-trending segment of the Sunsás orogen. This segment developed between Sucre in Bolivia and Corumbá in Brazil as a result of a Mesoproterozoic collision. The western margin of Pampia partially coincides with the southern part of the Arequipa-Antofalla terrane that was also amalgamated during the Mesoproterozoic. The Cuyania terrane, a Laurentian rifted continental block, was accreted to the southern sector of this margin of Pampia in middle Ordovician times. The northern sector of the eastern margin of Pampia is the lower plate of the Brasiliano belt developed along the Paranapanema craton during the early Cambrian collision associated with the closure of the Clymene Ocean. The southern sector of the eastern margin partially coincides with the southern extension of the Transbrasiliano lineament, which juxtaposed the Rio de La Plata Craton with the Pampia cratonic block. Along this eastern margin the Pampean-Paraguay orogen was formed during the late Brasiliano cycle in latest Proterozoic-Early Cambrian time. The southern margin was generated by the collision of Patagonia during late Paleozoic times. This cratonic block of Pampia, so defined, has western and northern sectors formed by Mesoproterozoic orogens, while the eastern sector is partially formed by juvenile Neoproterozoic crust, although older rocks cannot be ruled out. The Pampia cratonic block was the locus of several magmatic belts associated with important metamorphism during the Paleozoic and preserved in the central part at lower crustal levels.

  7. Blocking device especially for circulating pumps

    International Nuclear Information System (INIS)

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  8. Demographic Data - MDC_BlockGroup

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade County Census 2000 Block Groups. A census Block Group is a statistical subdivision of a census Tract consisting of a cluster of...

  9. Used, Blocking and Sleeping Patents

    DEFF Research Database (Denmark)

    Torrisi, Salvatore; Gambardella, Alfonso; Giuri, Paola

    2016-01-01

    patents are being utilized. A substantial share of patents is neither used internally nor for market transactions, which confirms the importance of strategic patenting and inefficiency in the management of intellectual property. We investigate different types of unused patents—unused blocking patents...... and sleeping patents. We also examine the association between used and unused patents and their characteristics such as family size, scope, generality and overlapping claims, technology area, type of applicant, and the competitive environment from where these patents originate. We discuss our results...

  10. Large block test status report

    International Nuclear Information System (INIS)

    Wilder, D.G.; Lin, W.; Blair, S.C.

    1997-01-01

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved

  11. Micellization and Dynamics of a Block Copolymer

    DEFF Research Database (Denmark)

    Hvidt, Søren

    2006-01-01

    Triblock copolymers of the type EPE, where E and P denote ethylene oxide and propylene oxide blocks, respectively, are industrially important copolymers often called Pluronics or Poloxamers. EPE copolymers form micelles with a core of P blocks and different micellar shapes depending on block leng...

  12. 31 CFR 515.319 - Blocked account.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account. 515.319 Section 515... § 515.319 Blocked account. The term blocked account shall mean an account in which any designated national has an interest, with respect to which account payments, transfers or withdrawals or other...

  13. 31 CFR 500.319 - Blocked account.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account. 500.319 Section 500... § 500.319 Blocked account. The term blocked account shall mean an account in which any designated national has an interest, with respect to which account payments, transfers or withdrawals of other...

  14. Bullet-Block Science Video Puzzle

    Science.gov (United States)

    Shakur, Asif

    2015-01-01

    A science video blog, which has gone viral, shows a wooden block shot by a vertically aimed rifle. The video shows that the block hit dead center goes exactly as high as the one shot off-center. (Fig. 1). The puzzle is that the block shot off-center carries rotational kinetic energy in addition to the gravitational potential energy. This leads a…

  15. 21 CFR 882.5070 - Bite block.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bite block. 882.5070 Section 882.5070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5070 Bite block. (a) Identification. A bite block...

  16. Adrenaline with lidocaine for digital nerve blocks.

    Science.gov (United States)

    Prabhakar, Hemanshu; Rath, Santosh; Kalaivani, Mani; Bhanderi, Neel

    2015-03-19

    Surgery on fingers is a common procedure in emergency and day care surgery. Adrenaline combined with lidocaine can prolong digital nerve block and provide a bloodless operating field. Extended postoperative pain relief can reduce the need for analgesics and can facilitate hand rehabilitation. Conventionally, adrenaline is avoided at anatomical sites with end arteries such as digits, penis and pinna because of concerns about arterial spasm, ischaemia and gangrene distal to the site of drug infiltration. To assess the safety and efficacy of use of adrenaline (any dilution) combined with lidocaine (any dilution) for digital nerve blocks (fingers and toes). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2014), MEDLINE via Ovid SP (1966 to 18 November 2014) and EMBASE via Ovid SP (1980 to 18 November 2014). We also searched specific websites, such as www.indmed.nic.in; www.cochrane-sadcct.org; and www.Clinicaltrials.gov. We included randomized controlled trials (RCTs) that compared the use of adrenaline with lidocaine and plain lidocaine in patients undergoing surgery on digits (fingers and toes). Our primary outcomes were duration of anaesthesia, adverse outcomes such as ischaemia distal to the injection site and cost analysis. Our secondary outcomes were duration of postoperative pain relief and reduced bleeding during surgery. We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. We performed all analyses on an intention-to-treat basis. We used a fixed-effect model when no evidence of significant heterogeneity between studies was found and a random-effects model when heterogeneity was likely. We included four RCTs with 167 participants. Risk of bias of the included studies was high, as none of them reported method of randomization, allocation concealment

  17. Finite-frequency sensitivity kernels of seismic waves to fault zone structures

    Science.gov (United States)

    Allam, A. A.; Tape, C.; Ben-Zion, Y.

    2015-12-01

    We analyse the volumetric sensitivity of fault zone seismic head and trapped waves by constructing finite-frequency sensitivity (Fréchet) kernels for these phases using a suite of idealized and tomographically derived velocity models of fault zones. We first validate numerical calculations by waveform comparisons with analytical results for two simple fault zone models: a vertical bimaterial interface separating two solids of differing elastic properties, and a `vertical sandwich' with a vertical low velocity zone surrounded on both sides by higher velocity media. Establishing numerical accuracy up to 12 Hz, we compute sensitivity kernels for various phases that arise in these and more realistic models. In contrast to direct P body waves, which have little or no sensitivity to the internal fault zone structure, the sensitivity kernels for head waves have sharp peaks with high values near the fault in the faster medium. Surface wave kernels show the broadest spatial distribution of sensitivity, while trapped wave kernels are extremely narrow with sensitivity focused entirely inside the low-velocity fault zone layer. Trapped waves are shown to exhibit sensitivity patterns similar to Love waves, with decreasing width as a function of frequency and multiple Fresnel zones of alternating polarity. In models that include smoothing of the boundaries of the low velocity zone, there is little effect on the trapped wave kernels, which are focused in the central core of the low velocity zone. When the source is located outside a shallow fault zone layer, trapped waves propagate through the surrounding medium with body wave sensitivity before becoming confined. The results provide building blocks for full waveform tomography of fault zone regions combining high-frequency head, trapped, body, and surface waves. Such an imaging approach can constrain fault zone structure across a larger range of scales than has previously been possible.

  18. Sensitivity, Recalculated

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, J. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-11-07

    Prior to this study, the sensitivity in nEXO was calculated using an approximate method that does not provide 90% coverage. I find it useful to understand the confidence level of a limit by focusing on the confidence level as a property of the method used to find the limit.A particular method (algorithm,formula) is applied to an experiment to produce a limit. That experiment was conducted in a particular universe with certain values of the physical parameters. We’d like a method than produces a correct limit for 90% of the experiments that could run. We also want that to be true for every universe—that is, regardless of the physical parameter value, the method should still produce a correct limit 90% of the time.

  19. Isostatic compression of buffer blocks. Middle scale

    International Nuclear Information System (INIS)

    Ritola, J.; Pyy, E.

    2012-01-01

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  20. Coastal protection using topological interlocking blocks

    Science.gov (United States)

    Pasternak, Elena; Dyskin, Arcady; Pattiaratchi, Charitha; Pelinovsky, Efim

    2013-04-01

    The coastal protection systems mainly rely on the self-weight of armour blocks to ensure its stability. We propose a system of interlocking armour blocks, which form plate-shape assemblies. The shape and the position of the blocks are chosen in such a way as to impose kinematic constraints that prevent the blocks from being removed from the assembly. The topological interlocking shapes include simple convex blocks such as platonic solids, the most practical being tetrahedra, cubes and octahedra. Another class of topological interlocking blocks is so-called osteomorphic blocks, which form plate-like assemblies tolerant to random block removal (almost 25% of blocks need to be removed for the assembly to loose integrity). Both classes require peripheral constraint, which can be provided either by the weight of the blocks or post-tensioned internal cables. The interlocking assemblies provide increased stability because lifting one block involves lifting (and bending) the whole assembly. We model the effect of interlocking by introducing an equivalent additional self-weight of the armour blocks. This additional self-weight is proportional to the critical pressure needed to cause bending of the interlocking assembly when it loses stability. Using beam approximation we find an equivalent stability coefficient for interlocking. It is found to be greater than the stability coefficient of a structure with similar blocks without interlocking. In the case when the peripheral constraint is provided by the weight of the blocks and for the slope angle of 45o, the effective stability coefficient for a structure of 100 blocks is 33% higher than the one for a similar structure without interlocking. Further increase in the stability coefficient can be reached by a specially constructed peripheral constraint system, for instance by using post-tension cables.

  1. Isostatic compression of buffer blocks. Middle scale

    Energy Technology Data Exchange (ETDEWEB)

    Ritola, J.; Pyy, E. [VTT Technical Research Centre of Finland, Espoo (Finland)

    2012-01-15

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  2. Randomized Block Cubic Newton Method

    KAUST Repository

    Doikov, Nikita

    2018-02-12

    We study the problem of minimizing the sum of three convex functions: a differentiable, twice-differentiable and a non-smooth term in a high dimensional setting. To this effect we propose and analyze a randomized block cubic Newton (RBCN) method, which in each iteration builds a model of the objective function formed as the sum of the natural models of its three components: a linear model with a quadratic regularizer for the differentiable term, a quadratic model with a cubic regularizer for the twice differentiable term, and perfect (proximal) model for the nonsmooth term. Our method in each iteration minimizes the model over a random subset of blocks of the search variable. RBCN is the first algorithm with these properties, generalizing several existing methods, matching the best known bounds in all special cases. We establish ${\\\\cal O}(1/\\\\epsilon)$, ${\\\\cal O}(1/\\\\sqrt{\\\\epsilon})$ and ${\\\\cal O}(\\\\log (1/\\\\epsilon))$ rates under different assumptions on the component functions. Lastly, we show numerically that our method outperforms the state-of-the-art on a variety of machine learning problems, including cubically regularized least-squares, logistic regression with constraints, and Poisson regression.

  3. Central effects of humanin on hepatic triglyceride secretion.

    Science.gov (United States)

    Gong, Zhenwei; Su, Kai; Cui, Lingguang; Tas, Emir; Zhang, Ting; Dong, H Henry; Yakar, Shoshana; Muzumdar, Radhika H

    2015-08-01

    Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism. Copyright © 2015 the American Physiological Society.

  4. Photochromic dye-sensitized solar cells

    Directory of Open Access Journals (Sweden)

    Noah M. Johnson

    2015-11-01

    Full Text Available We report the fabrication and characterization of photochromic dye sensitized solar cells that possess the ability to change color depending on external lighting conditions. This device can be used as a “smart” window shade that tints, collects the sun's energy, and blocks sunlight when the sun shines, and is completely transparent at night.

  5. ALS insertion device block measurement and inspection

    International Nuclear Information System (INIS)

    Marks, S.; Carrieri, J.; Cook, C.; Hassenzahl, W.V.; Hoyer, E.; Plate, D.

    1991-05-01

    The performance specifications for ALS insertion devices require detailed knowledge and strict control of the Nd-Fe-B permanent magnet blocks incorporated in these devices. This paper describes the measurement and inspection apparatus and the procedures designed to qualify and characterize these blocks. A detailed description of a new, automated Helmholtz coil facility for measurement of the three components of magnetic moment is included. Physical block inspection and magnetic moment measurement procedures are described. Together they provide a basis for qualifying blocks and for specifying placement of blocks within an insertion devices' magnetic structures. 1 ref., 4 figs

  6. Adaptive motion compensation without blocking artifacts

    Science.gov (United States)

    Terriberry, Timothy B.

    2015-03-01

    The Block Matching Algorithms used in most popular video codec standards introduce blocking artifacts which must be removed via residual coding or deblocking filters. Alternative transform stages that do not cause blocking artifacts, such as lapped transforms or wavelets, require motion compensation methods that do not produce blocking artifacts, since they are expensive to remove. We design a new Overlapped Block Motion Compensation (OBMC) scheme that avoids these artifacts while allowing adaptive blending window sizes. This has the potential to show significant visual quality improvements over traditional OBMC.

  7. Misgivings about the Matching Familiar Figures Test: A Brief Reply to Block, Gjerde, and Block (1986).

    Science.gov (United States)

    Kagan, Jerome

    1987-01-01

    Reply by Jerome Kagan to a recent article by Block, Gjerde, and Block (1986) which questions the validity of the construct of reflection-impulsivity. Kagan alleges flaws in the logic of the authors' (Block, Gjerde, Block) position and in the inferences drawn from their data. (Author/RWB)

  8. 31 CFR 544.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 544.204 Section 544.204 Money and Finance: Treasury... maintaining blocked physical property; liquidation of blocked property. (a) Except as otherwise authorized..., all expenses incident to the maintenance of physical property blocked pursuant to § 544.201(a) shall...

  9. 31 CFR 547.204 - Expenses of maintaining blocked physical property; liquidation of blocked property.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked property. 547.204 Section 547.204 Money and Finance: Treasury... maintaining blocked physical property; liquidation of blocked property. (a) Except as otherwise authorized..., all expenses incident to the maintenance of physical property blocked pursuant to § 547.201(a) shall...

  10. 31 CFR 593.204 - Expenses of maintaining blocked physical property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... physical property; liquidation of blocked account. 593.204 Section 593.204 Money and Finance: Treasury... maintaining blocked physical property; liquidation of blocked account. (a) Except as otherwise authorized, and... to the maintenance of physical property blocked pursuant to § 593.201(a) shall be the responsibility...

  11. 31 CFR 587.205 - Expenses of maintaining blocked property; liquidation of blocked account.

    Science.gov (United States)

    2010-07-01

    ... property; liquidation of blocked account. 587.205 Section 587.205 Money and Finance: Treasury Regulations....205 Expenses of maintaining blocked property; liquidation of blocked account. (a) Except as otherwise... standard time, January 19, 2001, all expenses incident to the maintenance of physical property blocked...

  12. Paravertebral Block for Inguinal Herniorrhaphy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Law, Lawrence Siu-Chun; Tan, Mingjuan; Bai, Yaowu; Miller, Timothy E; Li, Yi-Ju; Gan, Tong-Joo

    2015-08-01

    Paravertebral block (PVB) is a safe and effective anesthetic technique for thoracotomy and mastectomy. However, no systematic review or meta-analysis has focused on PVB for inguinal herniorrhaphy. Our study compares PVB with general anesthesia/systemic analgesia, neuraxial blocks, and other peripheral nerve blocks. We analyzed 14 randomized controlled trials from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL up to February 2015, without language restriction, comparing PVB under sedation with general anesthesia/systematic analgesia (135 vs 133 patients), neuraxial blocks (191 vs 186 patients), and other peripheral nerve blocks (119 vs 117 patients). We investigated pain scores, consumption of postoperative analgesia, incidence of postoperative nausea and vomiting (PONV), length of hospital stay, postanesthesia care unit bypassing rate, time to perform blocks, intraoperative hemodynamics, and incidence of urinary retention. Joint hypothesis testing was adopted for pain and analgesics, PONV, and hemodynamic variables. All analyses were performed with RevMan 5.2.11 (Cochrane Collaboration, Copenhagen). Hartung-Knapp-Sidik-Jonkman method was used for post hoc testing. PVB reduced PONV (nausea: risk ratio [RR] = 0.22; 95% confidence interval [CI], 0.05-0.93; numbers needed to treat [NNT] = 4.5; I = 15% and vomiting: RR = 0.15; 95% CI, 0.03-0.76; NNT = 8.3; I = 0%) compared with general anesthesia/systematic analgesia (quality of evidence [QoE]: high). Compared with neuraxial blocks, PVB resulted in less postoperative nausea (RR = 0.34 [95% CI, 0.13-0.91], NNT = 8.3, I = 0%) and urinary retention (RR = 0.14 [95% CI, 0.05-0.42], NNT = 7.4, I = 0%) than neuraxial blocks (QoE: high). More time was needed to perform PVB than neuraxial blocks (standardized mean difference = 1.90 [95% CI, 0.02-3.77], I = 92%; mean difference = 5.33 minutes; QoE: moderate). However, the available data could not reject the null hypothesis of noninferiority on all pain scores and analgesic

  13. Evidence that radio-sensitive cells are central to skin-phase protective immunity in CBA/Ca mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni as well as in naive mice protected with vaccine serum

    International Nuclear Information System (INIS)

    Delgado, V.S.; McLaren, D.J.

    1990-01-01

    Naive CBA/Ca mice and CBA/ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were subjected to 550 rad of whole body (gamma) irradiation and then challenged 3 days later with normal cercariae. The perfusion recovery data showed that this procedure reduced the primary worm burden in naive mice by 22% and the challence worm burden in vaccinated mice by 82%. Irradiation also ablated the peripheral blood leucocytes of both mouse groups by 90-100% at the time of challenge. Histological data revealed that such treatment caused a dramatic change in number, size and leucocyte composition of cutaneous inflammatory skin reactions that characterize challenged vacccinated mice and are known to entrap invading larvae; cutaneous eosinophils were preferentially abolished by this treatment. Polyvaccine mouse serum that conferred protection passively upon naive recipient mice, failed to protect naive/irradiated mice when administered by the same protocol. Distraction of macrophages by treatment of mice with silica did not affect the establishment of a primary worm burden and reduced the protection exhibited by vaccinated mice by only 16%. These data indicade that radio-sensitive cells are important to both innate and specific acquired resistance in this mouse model and that macrophages contribute only marginally to the expression of vaccine immunity. (author)

  14. Evidence that radio-sensitive cells are central to skin-phase protective immunity in CBA/Ca mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni as well as in naive mice protected with vaccine serum

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, V.S.; McLaren, D.J. (National Inst. for Medical Research, London (UK))

    1990-02-01

    Naive CBA/Ca mice and CBA/ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were subjected to 550 rad of whole body (gamma) irradiation and then challenged 3 days later with normal cercariae. The perfusion recovery data showed that this procedure reduced the primary worm burden in naive mice by 22% and the challence worm burden in vaccinated mice by 82%. Irradiation also ablated the peripheral blood leucocytes of both mouse groups by 90-100% at the time of challenge. Histological data revealed that such treatment caused a dramatic change in number, size and leucocyte composition of cutaneous inflammatory skin reactions that characterize challenged vacccinated mice and are known to entrap invading larvae; cutaneous eosinophils were preferentially abolished by this treatment. Polyvaccine mouse serum that conferred protection passively upon naive recipient mice, failed to protect naive/irradiated mice when administered by the same protocol. Distraction of macrophages by treatment of mice with silica did not affect the establishment of a primary worm burden and reduced the protection exhibited by vaccinated mice by only 16%. These data indicade that radio-sensitive cells are important to both innate and specific acquired resistance in this mouse model and that macrophages contribute only marginally to the expression of vaccine immunity. (author).

  15. Adults with patellofemoral pain do not exhibit manifestations of peripheral and central sensitization when compared to healthy pain-free age and sex matched controls - An assessor blinded cross-sectional study.