Smooth Pursuit Eye Movements in Children with Strabismus and in Children with Vergence Deficits

PubMed Central

Lions, Cynthia; Bui-Quoc, Emmanuel; Wiener-Vacher, Sylvette; Seassau, Magali; Bucci, Maria Pia

2013-01-01

Purpose The objective of our study was to examine horizontal smooth pursuit performance in strabismic children and in children with vergence deficits, and to compare these data with those recorded in a group of control age-matched children. Methods Binocular eye movements were recorded by video-oculography in ten strabismic children (mean age: 9.8±0.8) and seven children with vergence deficits (mean age: 10.8±0.6). Data were compared to that of age-matched control children (mean age: 9.8±0.8 years). Results Catch-up saccades amplitude in strabismic children and in children with vergence deficits were significantly higher than in control age-matched children. Moreover, in strabismic children the amplitude of catch-up saccades was significantly higher in rightward than in leftward direction. The number of catch-up saccades was also significantly higher in rightward than in leftward direction. The gain value of pursuits in rightward direction was significantly higher in the right eye than in the left one; for the right eye, the gain value was significantly higher in rightward than in leftward direction. Binocular coordination of pursuit was better in control age-matched children than in children with vergence deficits and than in strabismic children. Conclusions Binocular coordination of pursuit is abnormal in children with vergence deficits and worse in strabismic children. Binocular vision plays an important role in improving binocular coordination of pursuit. PMID:24376777

Differential shift in spatial bias over time depends on observers׳ initial bias: Observer subtypes, or regression to the mean?

PubMed

Newman, Daniel P; Loughnane, Gerard M; Abe, Rafael; Zoratti, Marco T R; Martins, Ana C P; van den Bogert, Petra C; Kelly, Simon P; O'Connell, Redmond G; Bellgrove, Mark A

2014-11-01

Healthy subjects typically exhibit a subtle bias of visuospatial attention favouring left space that is commonly termed 'pseudoneglect'. This bias is attenuated, or shifted rightwards, with decreasing alertness over time, consistent with theoretical models proposing that pseudoneglect is a result of the right hemisphere׳s dominance in regulating attention. Although this 'time-on-task effect' for spatial bias is observed when averaging across whole samples of healthy participants, Benwell, C. S. Y., Thut, G., Learmonth, G., & Harvey, M. (2013b). Spatial attention: differential shifts in pseudoneglect direction with time-on-task and initial bias support the idea of observer subtypes. Neuropsychologia, 51(13), 2747-2756 recently presented evidence that the direction and magnitude of bias exhibited by the participant early in the task (left biased, no bias, or right biased) were stable traits that predicted the direction of the subsequent time-on-task shift in spatial bias. That is, the spatial bias of participants who were initially left biased shifted in a rightward direction with time, whereas that of participants who were initially right biased shifted in a leftward direction. If valid, the data of Benwell et al. are potentially important and may demand a re-evaluation of current models of the neural networks governing spatial attention. Here we use two novel spatial attention tasks in an attempt to confirm the results of Benwell et al. We show that rather than being indicative of true participant subtypes, these data patterns are likely driven, at least in part, by 'regression towards the mean' arising from the analysis method employed. Although evidence supports the contention that trait-like individual differences in spatial bias exist within the healthy population, no clear evidence is yet available for participant/observer subtypes in the direction of time-on-task shift in spatial biases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-activity relationship studies of (+/-)-terbutaline and (+/-)-fenoterol on beta3-adrenoceptors in the guinea pig gastric fundus.

PubMed

Horinouchi, T; Nakagawa, Y; Wakabayashi, M; Koike, K

2001-08-01

(+/-)-Terbutaline and (+/-)-fenoterol are both arylethanolamine analogs that have tertbutyl and aryliso-propyl substituents respectively at the a position on the nitrogen of the ethanolamine side chain. In the present study, we have investigated the structure-activity relationships of (+/-)-terbutaline and (+/-)-fenoterol as beta3-adrenoceptor agonists in the guinea pig gastric fundus. (+/-)-Terbutaline and (+/-)-fenoterol induced concentration-dependent relaxation of the precontracted gastric fundus with pD2 values of 4.45+/-0.10 and 5.90+/-0.09, and intrinsic activities of 1.00+/-0.03 and 0.99+/-0.01 respectively. The combination of the selective beta1-adrenoceptor antagonist (+/-)-atenolol (100 microM), and the selective beta2-adrenoceptor antagonist (+/-)-butoxamine (100 microM), produced a 2 and 6 fold rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol respectively, without depressing the maximal responses. The order of potency of these agonists was (pD2 value): (+/-)-fenoterol (5.09+/-0.10) > (+/-)-terbutaline (4.13+/-0.08). In the presence of (+/-)-atenolol and (+/-)-butoxamine, however, the non-selective beta1, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol caused a concentration-dependent rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol. Schild plot analyses of the effects of (+/-)-bupranolol against these agonists gave pA2 values of 6.21+/-0.07 ((+/-)-terbutaline) and 6.37+/-0.06 ((+/-)-fenoterol) respectively, and the slopes of the Schild plot were not significantly different from unity (p>0.05). These results suggest that the relaxant responses to (+/-)-terbutaline and (+/-)-fenoterol are mainly mediated through beta3-adrenoceptors in the guinea pig gastric fundus. The beta3-adrenoceptor agonist potencies of arylethanolamine analogs depend on the size of the end of the alkylamine side chain.

Regional Changes in Word-Production Laterality after a Naming Treatment Designed to Produce a Rightward Shift in Frontal Activity

ERIC Educational Resources Information Center

Crosson, Bruce; Moore, Anna Bacon; McGregor, Keith M.; Chang, Yu-Ling; Benjamin, Michelle; Gopinath, Kaundinya; Sherod, Megan E.; Wierenga, Christina E.; Peck, Kyung K.; Briggs, Richard W.; Rothi, Leslie J. Gonzalez; White, Keith D.

2009-01-01

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying…

Shifting brain asymmetry: the link between meditation and structural lateralization.

PubMed

Kurth, Florian; MacKenzie-Graham, Allan; Toga, Arthur W; Luders, Eileen

2015-01-01

Previous studies have revealed an increased fractional anisotropy and greater thickness in the anterior parts of the corpus callosum in meditation practitioners compared with control subjects. Altered callosal features may be associated with an altered inter-hemispheric integration and the degree of brain asymmetry may also be shifted in meditation practitioners. Therefore, we investigated differences in gray matter asymmetry as well as correlations between gray matter asymmetry and years of meditation practice in 50 long-term meditators and 50 controls. We detected a decreased rightward asymmetry in the precuneus in meditators compared with controls. In addition, we observed that a stronger leftward asymmetry near the posterior intraparietal sulcus was positively associated with the number of meditation practice years. In a further exploratory analysis, we observed that a stronger rightward asymmetry in the pregenual cingulate cortex was negatively associated with the number of practice years. The group difference within the precuneus, as well as the positive correlations with meditation years in the pregenual cingulate cortex, suggests an adaptation of the default mode network in meditators. The positive correlation between meditation practice years and asymmetry near the posterior intraparietal sulcus may suggest that meditation is accompanied by changes in attention processing. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Reflexes from pulmonary arterial baroreceptors in dogs: interaction with carotid sinus baroreceptors

PubMed Central

Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

2011-01-01

Abstract In contrast to the reflex vasodilatation occurring in response to stimulation of baroreceptors in the aortic arch, carotid sinuses and coronary arteries, stimulation of receptors in the wall of pulmonary arteries results in reflex systemic vasoconstriction. It is rare for interventions to activate only one reflexogenic region, therefore we investigated how these two types of reflexes interact. In anaesthetized dogs connected to cardiopulmonary bypass, reflexogenic areas of the carotid sinuses, aortic arch and coronary arteries and the pulmonary artery were subjected to independently controlled pressures. Systemic perfusion pressure (SPP) measured in the descending aorta (constant flow) provided an index of systemic vascular resistance. In other experiments, sympathetic efferent neural activity was recorded in fibres dissected from the renal nerve (RSNA). Physiological increases in pulmonary arterial pressure (PAP) induced significant increases in SPP (+39.1 ± 10.4 mmHg) and RSNA (+17.6 ± 2.2 impulses s−1) whereas increases in carotid sinus pressure (CSP) induced significant decreases in SPP (−42.6 ± 10.8 mmHg) and RSNA (−42.8 ± 18.2 impulses s−1) (P < 0.05 for each comparison; paired t test). To examine possible interactions, PAP was changed at different levels of CSP in both studies. With CSP controlled at 124 ± 2 mmHg, the threshold, ‘set point’ and saturation pressures of the PAP–SPP relationship were higher than those with CSP at 60 ± 1 mmHg; this rightward shift was associated with a significant decrease in the reflex gain. Similarly, increasing CSP produced a rightward shift of the PAP–RSNA relationship, although the effect on reflex gain was inconsistent. Furthermore, the responses to changes in CSP were influenced by setting PAP at different levels; increasing the level of PAP from 5 ± 1 to 33 ± 3 mmHg significantly increased the set point and threshold pressures of the CSP–SPP relationship; the reflex gain was not affected. These results indicate the existence of interaction between pulmonary arterial and carotid sinus baroreceptor reflexes; physiological and pathological states that alter the stimulus to one may alter the reflex responses from the other. PMID:21690195

Hemoglobin P50 During a Simulated Ascent of Mt. Everest, Operation Everest II

DTIC Science & Technology

2007-01-01

With altitude, increased [2,3-DPG] shifts the dissociation curve rightward, but hypocap- nia and alkalosis move it leftward. We determined both...of 30 mmHg. However, in vivo P50 remained between 26 and 27 mmHg throughout due to pro- gressive hypocapnia and alkalosis . Calculations suggest that...were unpredictable at extreme altitude, espe- cially in the face of counterbalancing effects from progressive hyperventilation and alkalosis . It was

Prisms to travel in time: Investigation of time-space association through prismatic adaptation effect on mental time travel.

PubMed

Anelli, Filomena; Ciaramelli, Elisa; Arzy, Shahar; Frassinetti, Francesca

2016-11-01

Accumulating evidence suggests that humans process time and space in similar veins. Humans represent time along a spatial continuum, and perception of temporal durations can be altered through manipulations of spatial attention by prismatic adaptation (PA). Here, we investigated whether PA-induced manipulations of spatial attention can also influence more conceptual aspects of time, such as humans' ability to travel mentally back and forward in time (mental time travel, MTT). Before and after leftward- and rightward-PA, participants projected themselves in the past, present or future time (i.e., self-projection), and, for each condition, determined whether a series of events were located in the past or the future with respect to that specific self-location in time (i.e., self-reference). The results demonstrated that leftward and rightward shifts of spatial attention facilitated recognition of past and future events, respectively. These findings suggest that spatial attention affects the temporal processing of the human self. Copyright © 2016 Elsevier B.V. All rights reserved.

Sexual dimorphism of sulcal length asymmetry in the cerebrum of adult cynomolgus monkeys (Macaca fascicularis).

PubMed

Imai, Noritaka; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Sakata-Haga, Hiromi; Fukui, Yoshihiro

2011-12-01

The present study aimed to quantitatively clarify the gross anatomical asymmetry and sexual dimorphism of the cerebral hemispheres of cynomolgus monkeys. While the fronto-occipital length of the right and left cerebral hemispheres was not different between sexes, a statistically significant rightward asymmetry was detected in the cerebral width at the perisylvian region in females, but not in males (narrower width of the left side in the females). An asymmetry quotient of the sulcal lengths revealed a rightward asymmetry in the inferior occipital sulcus and a leftward asymmetry in the central and intraparietal sulci in both sexes. However, the laterality of the lengths of other sulci was different for males and females. The arcuate sulcus was directed rightward in males but there was no rightward bias in females. Interestingly, the principle sulcus and lateral fissure were left-lateralized in the males, but right-lateralized in the females. The results suggest that lateralization patterns are regionally and sexually different in the cerebrum of cynomolgus monkeys. The present results provide a reference for quantitatively evaluating the normality of the cerebral cortical morphology in cynomolgus monkeys. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

Plasticity of language-related brain function during recovery from stroke.

PubMed

Thulborn, K R; Carpenter, P A; Just, M A

1999-04-01

This study was undertaken to correlate functional recovery from aphasia after acute stroke with the temporal evolution of the anatomic, physiological, and functional changes as measured by MRI. Blood oxygenation level-dependent contrast and echo-planar MRI were used to map language comprehension in 6 normal adults and in 2 adult patients during recovery from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and conventional anatomic MRI were used to follow physiological and structural changes. The normal activation pattern for language comprehension showed activation predominately in left-sided Wernicke's and Broca's areas, with laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed as having a completed stroke affecting Broca's area occurred rapidly with a shift of activation to the homologous region in the right hemisphere within 3 days, with continued rightward lateralization over 6 months. In the second patient, in whom mapping was performed fortuitously before stroke, recovery of a Wernicke's aphasia showed a similar increasing rightward shift in activation recruitment over 9 months after the event. Recovery of aphasia in adults can occur rapidly and is concomitant with an activation pattern that changes from left to a homologous right hemispheric pattern. Such recovery occurs even when the stroke evolves to completion. Such plasticity must be considered when evaluating stroke interventions based on behavioral and neurological measurements.

Second-order processing of four-stroke apparent motion.

PubMed

Mather, G; Murdoch, L

1999-05-01

In four-stroke apparent motion displays, pattern elements oscillate between two adjacent positions and synchronously reverse in contrast, but appear to move unidirectionally. For example, if rightward shifts preserve contrast but leftward shifts reverse contrast, consistent rightward motion is seen. In conventional first-order displays, elements reverse in luminance contrast (e.g. light elements become dark, and vice-versa). The resulting perception can be explained by responses in elementary motion detectors turned to spatio-temporal orientation. Second-order motion displays contain texture-defined elements, and there is some evidence that they excite second-order motion detectors that extract spatio-temporal orientation following the application of a non-linear 'texture-grabbing' transform by the visual system. We generated a variety of second-order four-stroke displays, containing texture-contrast reversals instead of luminance contrast reversals, and used their effectiveness as a diagnostic test for the presence of various forms of non-linear transform in the second-order motion system. Displays containing only forward or only reversed phi motion sequences were also tested. Displays defined by variation in luminance, contrast, orientation, and size were effective. Displays defined by variation in motion, dynamism, and stereo were partially or wholly ineffective. Results obtained with contrast-reversing and four-stroke displays indicate that only relatively simple non-linear transforms (involving spatial filtering and rectification) are available during second-order energy-based motion analysis.

A comparative assessment of the duration of action of amlodipine and nifedipine GITS in normotensive subjects.

PubMed

Ueda, S; Meredith, P A; Howie, C A; Elliott, H L

1993-12-01

1 This study in normotensive subjects compared the duration and consistency of action of amlodipine (5 mg) and nifedipine GITS (60 mg) by assessment of the attenuation of pressor responses to noradrenaline and angiotensin II. 2 Both drugs significantly attenuated pressor responses to both vasoconstrictors at 6 and 24 h post-dose with rightward shifts of up to 2.3-fold in the dose-response curves. 3 There was significantly less pharmacokinetic variability with amlodipine: for example, intra-subject variability was 33% with amlodipine and 59% with nifedipine GITS. 4 There were no significant differences in the pressor dose ratios up to 48 h post-dose with amlodipine whereas there was a significant and progressive reduction in the pressor dose ratios with nifedipine. 5 These results suggest that both drugs are broadly comparable as once daily treatments but amlodipine displayed less intra- and inter-subject variability and provided a significantly more sustained effect with a reserve of pharmacological activity up to 48 h post-dose.

Interactions of numerical and temporal stimulus characteristics on the control of response location by brief flashes of light.

PubMed

Fetterman, J Gregor; Killeen, P Richard

2011-09-01

Pigeons pecked on three keys, responses to one of which could be reinforced after 3 flashes of the houselight, to a second key after 6, and to a third key after 12. The flashes were arranged according to variable-interval schedules. Response allocation among the keys was a function of the number of flashes. When flashes were omitted, transitions occurred very late. Increasing flash duration produced a leftward shift in the transitions along a number axis. Increasing reinforcement probability produced a leftward shift, and decreasing reinforcement probability produced a rightward shift. Intermixing different flash rates within sessions separated allocations: Faster flash rates shifted the functions sooner in real time, but later in terms of flash count, and conversely for slower flash rates. A model of control by fading memories of number and time was proposed.

Evoking visual neglect-like deficits in healthy volunteers - an investigation by repetitive navigated transcranial magnetic stimulation.

PubMed

Giglhuber, Katrin; Maurer, Stefanie; Zimmer, Claus; Meyer, Bernhard; Krieg, Sandro M

2017-02-01

In clinical practice, repetitive navigated transcranial magnetic stimulation (rTMS) is of particular interest for non-invasive mapping of cortical language areas. Yet, rTMS studies try to detect further cortical functions. Damage to the underlying network of visuospatial attention function can result in visual neglect-a severe neurological deficit and influencing factor for a significantly reduced functional outcome. This investigation aims to evaluate the use of rTMS for evoking visual neglect in healthy volunteers and the potential of specifically locating cortical areas that can be assigned for the function of visuospatial attention. Ten healthy, right-handed subjects underwent rTMS visual neglect mapping. Repetitive trains of 5 Hz and 10 pulses were applied to 52 pre-defined cortical spots on each hemisphere; each cortical spot was stimulated 10 times. Visuospatial attention was tested time-locked to rTMS pulses by a landmark task. Task pictures were displayed tachistoscopically for 50 ms. The subjects' performance was analyzed by video, and errors were referenced to cortical spots. We observed visual neglect-like deficits during the stimulation of both hemispheres. Errors were categorized into leftward, rightward, and no response errors. Rightward errors occurred significantly more often during stimulation of the right hemisphere than during stimulation of the left hemisphere (mean rightward error rate (ER) 1.6 ± 1.3 % vs. 1.0 ± 1.0 %, p = 0.0141). Within the left hemisphere, we observed predominantly leftward errors rather than rightward errors (mean leftward ER 2.0 ± 1.3 % vs. rightward ER 1.0 ± 1.0 %; p = 0.0005). Visual neglect can be elicited non-invasively by rTMS, and cortical areas eloquent for visuospatial attention can be detected. Yet, the correlation of this approach with clinical findings has to be shown in upcoming steps.

Early and Late Shift of Brain Laterality in STG, HG, and Cerebellum with Normal Aging during a Short-Term Memory Task

PubMed Central

Abdul Manan, Hanani; Yusoff, Ahmad Nazlim; Franz, Elizabeth A.; Sarah Mukari, Siti Zamratol-Mai

2013-01-01

Evidence suggests that cognitive performance deteriorates in noisy backgrounds and the problems are more pronounced in older people due to brain deficits and changes. The present study used functional MRI (fMRI) to investigate the neural correlates of this phenomenon during short-term memory using a forward repeat task performed in quiet (STMQ) and in noise: 5-dB SNR (STMN) on four groups of participants of different ages. The performance of short-term memory tasks was measured behaviourally. No significant difference was found across age groups in STMQ. However, older adults (50–65 year olds) performed relatively poorly on the STMN. fMRI results on the laterality index indicate changes in hemispheric laterality in the superior temporal gyrus (STG), Heschl's gyrus (HG), and cerebellum, and a leftward asymmetry in younger participants which changes to a more rightward asymmetry in older participants. The results also indicate that the onset of the laterality shift varies from one brain region to another. STG and HG show a late shift while the cerebellum shows an earlier shift. The results also reveal that noise influences this shifting. Finally, the results support the hypothesis that functional networks that underlie STG, HG, and cerebellum undergo reorganization to compensate for the neural deficit/cognitive decline. PMID:23533806

Coupling of G Proteins to Reconstituted Monomers and Tetramers of the M2 Muscarinic Receptor*

PubMed Central

Redka, Dar'ya S.; Morizumi, Takefumi; Elmslie, Gwendolynne; Paranthaman, Pranavan; Shivnaraine, Rabindra V.; Ellis, John; Ernst, Oliver P.; Wells, James W.

2014-01-01

G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5′-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[3H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the “ternary complex model”). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins. PMID:25023280

Coupling of g proteins to reconstituted monomers and tetramers of the M2 muscarinic receptor.

PubMed

Redka, Dar'ya S; Morizumi, Takefumi; Elmslie, Gwendolynne; Paranthaman, Pranavan; Shivnaraine, Rabindra V; Ellis, John; Ernst, Oliver P; Wells, James W

2014-08-29

G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5'-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[(3)H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the "ternary complex model"). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Competitive action video game players display rightward error bias during on-line video game play.

PubMed

Roebuck, Andrew J; Dubnyk, Aurora J B; Cochran, David; Mandryk, Regan L; Howland, John G; Harms, Victoria

2017-09-12

Research in asymmetrical visuospatial attention has identified a leftward bias in the general population across a variety of measures including visual attention and line-bisection tasks. In addition, increases in rightward collisions, or bumping, during visuospatial navigation tasks have been demonstrated in real world and virtual environments. However, little research has investigated these biases beyond the laboratory. The present study uses a semi-naturalistic approach and the online video game streaming service Twitch to examine navigational errors and assaults as skilled action video game players (n = 60) compete in Counter Strike: Global Offensive. This study showed a significant rightward bias in both fatal assaults and navigational errors. Analysis using the in-game ranking system as a measure of skill failed to show a relationship between bias and skill. These results suggest that a leftward visuospatial bias may exist in skilled players during online video game play. However, the present study was unable to account for some factors such as environmental symmetry and player handedness. In conclusion, video game streaming is a promising method for behavioural research in the future, however further study is required before one can determine whether these results are an artefact of the method applied, or representative of a genuine rightward bias.

Prismatic Adaptation Induces Plastic Changes onto Spatial and Temporal Domains in Near and Far Space.

PubMed

Patané, Ivan; Farnè, Alessandro; Frassinetti, Francesca

2016-01-01

A large literature has documented interactions between space and time suggesting that the two experiential domains may share a common format in a generalized magnitude system (ATOM theory). To further explore this hypothesis, here we measured the extent to which time and space are sensitive to the same sensorimotor plasticity processes, as induced by classical prismatic adaptation procedures (PA). We also exanimated whether spatial-attention shifts on time and space processing, produced through PA, extend to stimuli presented beyond the immediate near space. Results indicated that PA affected both temporal and spatial representations not only in the near space (i.e., the region within which the adaptation occurred), but also in the far space. In addition, both rightward and leftward PA directions caused opposite and symmetrical modulations on time processing, whereas only leftward PA biased space processing rightward. We discuss these findings within the ATOM framework and models that account for PA effects on space and time processing. We propose that the differential and asymmetrical effects following PA may suggest that temporal and spatial representations are not perfectly aligned.

Effect of target animacy on hand preference in Sichuan snub-nosed monkeys (Rhinopithecus roxellana).

PubMed

Zhao, Dapeng; Tian, Xiangling; Liu, Xinchen; Chen, Zhuoyue; Li, Baoguo

2016-09-01

Twenty-eight captive Sichuan snub-nosed monkeys (Rhinopithecus roxellana) were involved in the current study. Many individuals showed handedness, with a modest tendency toward left-hand use especially for animate targets, although no group-level handedness was found. There was no significant gender difference in the direction and strength of hand preference for both targets. Females showed a significantly higher overall rate of actions toward animate targets than inanimate targets for both hands, whereas males displayed almost the reversed pattern. There were no significant interactions between lateral hand use and target animacy for either males or females. Most individuals showed rightward or leftward laterality shift trends between inanimate and animate targets. These findings to some extent support the existence of a potential trend concerning a categorical neural distinction between targets demanding functional manipulation (inanimate objects) and those demanding social manipulation (animate objects), even though specialized hand preference based on target animacy has not been fully established in this arboreal Old World monkey species.

Effects of exercise pressor reflex activation on carotid baroreflex function during exercise in humans

NASA Technical Reports Server (NTRS)

Gallagher, K. M.; Fadel, P. J.; Stromstad, M.; Ide, K.; Smith, S. A.; Querry, R. G.; Raven, P. B.; Secher, N. H.

2001-01-01

1. This investigation was designed to determine the contribution of the exercise pressor reflex to the resetting of the carotid baroreflex during exercise. 2. Ten subjects performed 3.5 min of static one-legged exercise (20 % maximal voluntary contraction) and 7 min dynamic cycling (20 % maximal oxygen uptake) under two conditions: control (no intervention) and with the application of medical anti-shock (MAS) trousers inflated to 100 mmHg (to activate the exercise pressor reflex). Carotid baroreflex function was determined at rest and during exercise using a rapid neck pressure/neck suction technique. 3. During exercise, the application of MAS trousers (MAS condition) increased mean arterial pressure (MAP), plasma noradrenaline concentration (dynamic exercise only) and perceived exertion (dynamic exercise only) when compared to control (P < 0.05). No effect of the MAS condition was evident at rest. The MAS condition had no effect on heart rate (HR), plasma lactate and adrenaline concentrations or oxygen uptake at rest and during exercise. The carotid baroreflex stimulus-response curve was reset upward on the response arm and rightward to a higher operating pressure by control exercise without alterations in gain. Activation of the exercise pressor reflex by MAS trousers further reset carotid baroreflex control of MAP, as indicated by the upward and rightward relocation of the curve. However, carotid baroreflex control of HR was only shifted rightward to higher operating pressures by MAS trousers. The sensitivity of the carotid baroreflex was unaltered by exercise pressor reflex activation. 4. These findings suggest that during dynamic and static exercise the exercise pressor reflex is capable of actively resetting carotid baroreflex control of mean arterial pressure; however, it would appear only to modulate carotid baroreflex control of heart rate.

Left-handers' struggle in a rightward wor(l)d: The relation between horizontal spatial bias and effort in directed movements.

PubMed

Suitner, Caterina; Maass, Anne; Bettinsoli, Maria Laura; Carraro, Luciana; Kumar, Serena

2017-01-01

Five studies investigated the role of handedness and effort in horizontal spatial bias related to agency (Spatial Agency Bias, SAB). A Pilot Study (n = 33) confirmed the basic assumption that rightward writing requires greater effort from left- than from right-handers. In three studies, Italian students (n = 591 right-handed, n = 115 left-handed) were found to start drawings on the left, proceeding rightward (Study 1a, 1b), and to draw moving objects with a rightward orientation in line with script direction (Study 1c). These spatial asymmetries were displayed stronger by left- than by right-handed primacy school children, arguably due to the greater effort involved in learning how to write in a rightward fashion. Once writing has become fully automatic (high school) right- and left-handed students showed comparable spatial bias (Study 1c). The hypothesized role of effort was tested explicitly in Study 2 in which 99 right-handed adults learned a new (leftward) spatial trajectory through an easy or difficult motor exercise. The habitual rightward bias was reliably reduced, especially among those who performed a difficult task requiring greater effort. Together, findings are largely in line with the body specificity hypothesis (Casasanto, 2011 ) and suggest that spatial asymmetries are learned and unlearned most efficiently through effortful motor exercises.

Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.

PubMed

Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

2014-04-01

We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.

Kinematic markers dissociate error correction from sensorimotor realignment during prism adaptation.

PubMed

O'Shea, Jacinta; Gaveau, Valérie; Kandel, Matthieu; Koga, Kazuo; Susami, Kenji; Prablanc, Claude; Rossetti, Yves

2014-03-01

This study investigated the motor control mechanisms that enable healthy individuals to adapt their pointing movements during prism exposure to a rightward optical shift. In the prism adaptation literature, two processes are typically distinguished. Strategic motor adjustments are thought to drive the pattern of rapid endpoint error correction typically observed during the early stage of prism exposure. This is distinguished from so-called 'true sensorimotor realignment', normally measured with a different pointing task, at the end of prism exposure, which reveals a compensatory leftward 'prism after-effect'. Here, we tested whether each mode of motor compensation - strategic adjustments versus 'true sensorimotor realignment' - could be distinguished, by analyzing patterns of kinematic change during prism exposure. We hypothesized that fast feedforward versus slower feedback error corrective processes would map onto two distinct phases of the reach trajectory. Specifically, we predicted that feedforward adjustments would drive rapid compensation of the initial (acceleration) phase of the reach, resulting in the rapid reduction of endpoint errors typically observed early during prism exposure. By contrast, we expected visual-proprioceptive realignment to unfold more slowly and to reflect feedback influences during the terminal (deceleration) phase of the reach. The results confirmed these hypotheses. Rapid error reduction during the early stage of prism exposure was achieved by trial-by-trial adjustments of the motor plan, which were proportional to the endpoint error feedback from the previous trial. By contrast, compensation of the terminal reach phase unfolded slowly across the duration of prism exposure. Even after 100 trials of pointing through prisms, adaptation was incomplete, with participants continuing to exhibit a small rightward shift in both the reach endpoints and in the terminal phase of reach trajectories. Individual differences in the degree of adaptation of the terminal reach phase predicted the magnitude of prism after-effects. In summary, this study identifies distinct kinematic signatures of fast strategic versus slow sensorimotor realignment processes, which combine to adjust motor performance to compensate for a prismatic shift. © 2013 Elsevier Ltd. All rights reserved.

Calcium antagonistic activity of Bacopa monniera in guinea-pig trachea.

PubMed

Channa, Shabana; Dar, Ahsana

2012-01-01

To demonstrate the calcium antagonistic property of ethanol extract of Bacopa monniera in guinea-pig trachea. The dose response curves of CaCl(2) (1 × 10(-5) to 1 × 10(-1) M) were constructed in the absence and presence of ethanol extract of Bacopa monniera (100, 500 and 700 μg/ml) or nifedipine (1 × 10(-6) M) in guinea-pig trachea in calcium free high K(+)-MOPS-PSS (3-(N-morpholino)-propanesulphonic acid physiological salt solution). The data was analyzed by ANOVA followed by least significant difference test or by Student's 't' test for unequal variance when appropriate. A probability of at least P < 0.05 was considered statistically significant. The plant extract (500 and 700 μg/ml) significantly (P < 0.05) depressed and shifted the calcium concentration-response curves (1 × 10(-3)- 1 × 10(-1) M) to rightward similar to that of nifedipine. Bacopa monniera extract exhibited calcium channel blocking activity in guinea-pig tracheal smooth muscles that may rationalize its relaxant action on guinea-pig trachea and its traditional use in respiratory disorders.

Role of endothelin-converting enzyme, chymase and neutral endopeptidase in the processing of big ET-1, ET-1(1-21) and ET-1(1-31) in the trachea of allergic mice.

PubMed

De Campo, Benjamin A; Goldie, Roy G; Jeng, Arco Y; Henry, Peter J

2002-08-01

The present study examined the roles of endothelin-converting enzyme (ECE), neutral endopeptidase (NEP) and mast cell chymase as processors of the endothelin (ET) analogues ET-1(1-21), ET-1(1-31) and big ET-1 in the trachea of allergic mice. Male CBA/CaH mice were sensitized with ovalbumin (10 microg) delivered intraperitoneal on days 1 and 14, and exposed to aerosolized ovalbumin on days 14, 25, 26 and 27 (OVA mice). Mice were killed and the trachea excised for histological analysis and contraction studies on day 28. Tracheae from OVA mice had 40% more mast cells than vehicle-sensitized mice (sham mice). Ovalbumin (10 microg/ml) induced transient contractions (15+/-3% of the C(max)) in tracheae from OVA mice. The ECE inhibitor CGS35066 (10 microM) inhibited contractions induced by big ET-1 (4.8-fold rightward shift of dose-response curve; P<0.05), but not those induced by either ET-1(1-21) or ET-1(1-31). The chymase inhibitors chymostatin (10 microM) and Bowman-Birk inhibitor (10 microM) had no effect on contractions induced by any of the ET analogues used. The NEP inhibitor CGS24592 (10 microM) inhibited contractions induced by ET-1(1-31) (6.2-fold rightward shift; P<0.05) but not ET-1(1-21) or big ET-1. These data suggest that big ET-1 is processed predominantly by a CGS35066-sensitive ECE within allergic airways rather than by mast cell-derived proteases such as chymase. If endogenous ET-1(1-31) is formed within allergic airways, it is likely to undergo further conversion by NEP to more active products.

Protection from Muscle Damage in the Absence of Changes in Muscle Mechanical Behavior.

PubMed

Hoffman, Ben W; Cresswell, Andrew G; Carroll, Timothy J; Lichtwark, Glen A

2016-08-01

The repeated bout effect characterizes the protective adaptation after a single bout of unaccustomed eccentric exercise that induces muscle damage. Sarcomerogenesis and increased tendon compliance have been suggested as potential mechanisms for the repeated bout effect by preventing muscle fascicles from being stretched onto the descending limb of the length-tension curve (the region where sarcomere damage is thought to occur). In this study, evidence was sought for three possible mechanical changes that would support either the sarcomerogenesis or the increased tendon compliance hypotheses: a sustained rightward shift in the fascicle length-tension relationship, reduced fascicle strain amplitude, and reduced starting fascicle length. Subjects (n = 10) walked backward downhill (5 km·h, 20% incline) on a treadmill for 30 min on two occasions separated by 7 d. Kinematic data and medial gastrocnemius fascicle lengths (ultrasonography) were recorded at 10-min intervals to compare fascicle strains between bouts. Fascicle length-torque curves from supramaximal tibial nerve stimulation were constructed before, 2 h after, and 2 d after each exercise bout. Maximum torque decrement and elevated muscle soreness were present after the first, but not the second, backward downhill walking bout signifying a protective repeated bout effect. There was no sustained rightward shift in the length-torque relationship between exercise bouts, nor decreases in fascicle strain amplitude or shortening of the starting fascicle length. Protection from a repeated bout of eccentric exercise was conferred without changes in muscle fascicle strain behavior, indicating that sarcomerogenesis and increased tendon compliance were unlikely to be responsible. As fascicle strains are relatively small in humans, we suggest that changes to connective tissue structures, such as extracellular matrix remodeling, are better able to explain the repeated bout effect observed here.

Extended Asymmetrical Pedicle Subtraction Osteotomy for Adult Spinal Deformity: 2-Dimensional Operative Video.

PubMed

Buell, Thomas J; Buchholz, Avery L; Quinn, John C; Mullin, Jeffrey P; Garces, Juanita; Mazur, Marcus D; Shaffrey, Mark E; Yen, Chun-Po; Shaffrey, Christopher I; Smith, Justin S

2018-06-16

Pedicle subtraction osteotomy (PSO) is an effective technique to correct fixed sagittal malalignment. A variation of this technique, the "trans-discal" or "extended" PSO (Schwab grade IV osteotomy), involves extending the posterior wedge resection of the index vertebra to include the superior adjacent disc for radical discectomy. The posterior wedge may be resected in asymmetric fashion to correct concurrent global coronal malalignment.This video illustrates the technical nuances of an extended asymmetrical lumbar PSO for adult spinal deformity. A 62-yr-old female with multiple prior lumbar fusions presented with worsening back pain and posture. Preoperative scoliosis X-rays demonstrated severe global sagittal and coronal malalignment (sagittal vertical axis [SVA, C7-plumbline] of 13.5 cm, pelvic incidence [PI] of 60°, lumbar lordosis [LL] of 14° [in kyphosis], pelvic tilt [PT] of 61°, thoracic kyphosis [TK] of 18°, and rightward coronal shift of 9.3 cm). The patient gave informed consent to surgery and for use of her imaging for medical publication. Briefly, surgery first involved transpedicular instrumentation from T10 to S1 with bilateral iliac screw fixation, and then T11-12 and T12-L1 Smith-Petersen osteotomies were performed. Next, an extended asymmetrical L4 PSO was performed and a 12° lordotic cage (9 × 14 × 40 mm) was placed at the PSO defect. Rods were placed from T10 to iliac bilaterally, and accessory supplemental rods spanning the PSO were attached. Postoperative scoliosis X-rays demonstrated improved alignment: SVA 5.5 cm, PI 60°, LL 55°, PT 36°, TK 37°, and 3.7 cm of rightward coronal shift. The patient had uneventful recovery.

Asymmetric bias in perception of facial affect among Roman and Arabic script readers.

PubMed

Heath, Robin L; Rouhana, Aida; Ghanem, Dana Abi

2005-01-01

The asymmetric chimeric faces test is used frequently as an indicator of right hemisphere involvement in the perception of facial affect, as the test is considered free of linguistic elements. Much of the original research with the asymmetric chimeric faces test was conducted with subjects reading left-to-right Roman script, i.e., English. As readers of right-to-left scripts, such as Arabic, demonstrated a mixed or weak rightward bias in judgements of facial affect, the influence of habitual scanning direction was thought to intersect with laterality. We administered the asymmetric chimeric faces test to 1239 adults who represented a range of script experience, i.e., Roman script readers (English and French), Arabic readers, bidirectional readers of Roman and Arabic scripts, and illiterates. Our findings supported the hypothesis that the bias in facial affect judgement is rooted in laterality, but can be influenced by script direction. Specifically, right-handed readers of Roman script demonstrated the greatest mean leftward score, and mixed-handed Arabic script readers demonstrated the greatest mean rightward score. Biliterates showed a gradual shift in asymmetric perception, as their scores fell between those of Roman and Arabic script readers, basically distributed in the order expected by their handedness and most often used script. Illiterates, whose only directional influence was laterality, showed a slight leftward bias.

Line and word bisection in right-brain-damaged patients with left spatial neglect.

PubMed

Veronelli, Laura; Vallar, Giuseppe; Marinelli, Chiara V; Primativo, Silvia; Arduino, Lisa S

2014-01-01

Right-brain-damaged patients with left unilateral spatial neglect typically set the mid-point of horizontal lines to the right of the objective center. By contrast, healthy participants exhibit a reversed bias (pseudoneglect). The same effect has been described also when bisecting orthographic strings. In particular, for this latter kind of stimulus, some recent studies have shown that visuo-perceptual characteristics, like stimulus length, may contribute to both the magnitude and the direction bias of the bisection performance (Arduino et al. in Neuropsychologia 48:2140-2146, 2010). Furthermore, word stress was shown to modulate reading performances in both healthy participants, and patients with left spatial neglect and neglect dyslexia (Cubelli and Beschin in Brain Lang 95:319-326, 2005; Rusconi et al. in Neuropsychology 18:135-140, 2004). In Experiment I, 22 right-brain-damaged patients (11 with left visuo-spatial neglect) and 11 matched neurologically unimpaired control participants were asked to set the subjective mid-point of word letter strings, and of lines of comparable length. Most patients exhibited an overall disproportionate rightward bias, sensitive to stimulus length, and similar for words and lines. Importantly, in individual patients, biases differed according to stimulus type (words vs. lines), indicating that at least partly different mechanisms may be involved. In Experiment II, the putative effects on the bisection bias of ortho-phonological information (i.e., word stress endings), arising from the non-neglected right hand side of the stimulus were investigated. The orthographic cue induced a rightward shift of the perceived mid-point in both patients and controls, with short words stressed on the antepenultimate final sequence inducing a smaller rightward deviation with respect to short words stressed on the penultimate final sequence. In conclusion, partly different mechanisms, including both visuo-spatial and lexical factors, may support line and word bisection performance of right-brain-damaged patients with left spatial neglect, and healthy participants.

Laterality patterns of brain functional connectivity: gender effects.

PubMed

Tomasi, Dardo; Volkow, Nora D

2012-06-01

Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism).

Laterality Patterns of Brain Functional Connectivity: Gender Effects

PubMed Central

Tomasi, Dardo; Volkow, Nora D.

2012-01-01

Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism). PMID:21878483

Pupil Dilations Reflect Why Rembrandt Biased Female Portraits Leftward and Males Rightward

PubMed Central

Schirillo, James A.

2014-01-01

Portrait painters are experts at examining faces and since emotional content may be expressed differently on each side of the face, consider that Rembrandt biased his male portraits to show their right-cheek more often and female portraits to show their left-cheek more often. This raises questions regarding the emotional significance of such biased positions. I presented rightward and leftward facing male and female portraits. I measured observers’ pupil size while asking observers to report how (dis)pleasing they found each image. This was a methodological improvement over the type of research initially done by Eckhard Hess who claimed that pupils dilate to pleasant images and constrict to unpleasant images. His work was confounded since his images’ luminances and contrasts across conditions were inconsistent potentially affecting pupil size. To overcome this limitation I presented rightward or leftward facing male and female portraits by Rembrandt to observers in either their original or mirror-reversed position. I found that in viewing male portraits pupil diameter was a function of arousal. That is, larger pupil diameter occurred for images rated both low and high in pleasantness. This was not the case with female portraits. I discuss these findings in regard to the perceived dominance of males and how emotional expressions may be driven by hemispheric laterality. PMID:24454285

Calcium antagonistic activity of Bacopa monniera in guinea-pig trachea

PubMed Central

Channa, Shabana; Dar, Ahsana

2012-01-01

Objective: To demonstrate the calcium antagonistic property of ethanol extract of Bacopa monniera in guinea-pig trachea. Materials and Methods: The dose response curves of CaCl2 (1 × 10-5 to 1 × 10-1 M) were constructed in the absence and presence of ethanol extract of Bacopa monniera (100, 500 and 700 μg/ml) or nifedipine (1 × 10-6 M) in guinea-pig trachea in calcium free high K+-MOPS-PSS (3-(N-morpholino)-propanesulphonic acid physiological salt solution). The data was analyzed by ANOVA followed by least significant difference test or by Student's ‘t’ test for unequal variance when appropriate. A probability of at least P < 0.05 was considered statistically significant. Results: The plant extract (500 and 700 μg/ml) significantly (P < 0.05) depressed and shifted the calcium concentration-response curves (1 × 10-3- 1 × 10-1 M) to rightward similar to that of nifedipine. Conclusions: Bacopa monniera extract exhibited calcium channel blocking activity in guinea-pig tracheal smooth muscles that may rationalize its relaxant action on guinea-pig trachea and its traditional use in respiratory disorders. PMID:23087517

Jet formation of SF6 bubble induced by incident and reflected shock waves

NASA Astrophysics Data System (ADS)

Zhu, Yuejin; Yu, Lei; Pan, Jianfeng; Pan, Zhenhua; Zhang, Penggang

2017-12-01

The computational results of two different cases on the evolution of the shock-SF6 heavy bubble interaction are presented. The shock focusing processes and jet formation mechanisms are analyzed by using the high resolution of computation schemes, and the influence of reflected shock waves is also investigated. It is concluded that there are two steps in the shock focusing process behind the incident shock wave, and the density and pressure values increase distinctly when the shock focusing process is completed. The local high pressure and vorticities in the vicinity of the downstream pole can propel the formation of the jet behind the incident shock wave. In addition, the gas is with the rightward velocity before the reflected shock wave impinges on the bubble; therefore, the evolutions of the waves and the bubble are more complicated when the reflected shock wave impinges on the SF6 bubble. Furthermore, the different end wall distances would affect the deformation degree of the bubble before the interaction of the reflected shock wave; therefore, the different left jet formation processes are found after the impingement of reflected shock waves when L = 27 mm. The local high pressure zones in the vicinity of the left bubble interface and the impingement of different shock waves can induce the local gas to shift the rightward velocity to the leftward velocity, which can further promote the formation of jets.

Fe2O3 nanoparticles suppress Kv1.3 channels via affecting the redox activity of Kvβ2 subunit in Jurkat T cells

NASA Astrophysics Data System (ADS)

Yan, Li; Liu, Xiao; Liu, Wei-Xia; Tan, Xiao-Qiu; Xiong, Fei; Gu, Ning; Hao, Wei; Gao, Xue; Cao, Ji-Min

2015-12-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising nanomaterials in medical practice due to their special magnetic characteristics and nanoscale size. However, their potential impacts on immune cells are not well documented. This study aims to investigate the effects of Fe2O3 nanoparticles (Fe2O3-NPs) on the electrophysiology of Kv1.3 channels in Jurkat T cells. Using the whole-cell patch-clamp technique, we demonstrate that incubation of Jurkat cells with Fe2O3-NPs dose- and time-dependently decreased the current density and shifted the steady-state inactivation curve and the recovery curve of Kv1.3 channels to a rightward direction. Fe2O3-NPs increased the NADP level but decreased the NADPH level of Jurkat cells. Direct induction of NADPH into the cytosole of Jurkat cells via the pipette abolished the rightward shift of the inactivation curve. In addition, transmission electron microscopy showed that Fe2O3-NPs could be endocytosed by Jurkat cells with relatively low speed and capacity. Fe2O3-NPs did not significantly affect the viability of Jurkat cells, but suppressed the expressions of certain cytokines (TNFα, IFNγ and IL-2) and interferon responsive genes (IRF-1 and PIM-1), and the time courses of Fe2O3-NPs endocytosis and effects on the expressions of cytokines and interferon responsive genes were compatible. We conclude that Fe2O3-NPs can be endocytosed by Jurkat cells and act intracellularly. Fe2O3-NPs decrease the current density and delay the inactivation and recovery kinetics of Kv1.3 channels in Jurkat cells by oxidizing NADPH and therefore disrupting the redox activity of the Kvβ2 auxiliary subunit, and as a result, lead to changes of the Kv1.3 channel function. These results suggest that iron oxide nanoparticles may affect T cell function by disturbing the activity of Kv1.3 channels. Further, the suppressing effects of Fe2O3-NPs on the expressions of certain inflammatory cytokines and interferon responsive genes suggest that iron oxide nanoparticles may exert modulatory effects on T cell immune activities and anti-inflammation effects.

Does gravity influence the visual line bisection task?

PubMed

Drakul, A; Bockisch, C J; Tarnutzer, A A

2016-08-01

The visual line bisection task (LBT) is sensitive to perceptual biases of visuospatial attention, showing slight leftward (for horizontal lines) and upward (for vertical lines) errors in healthy subjects. It may be solved in an egocentric or allocentric reference frame, and there is no obvious need for graviceptive input. However, for other visual line adjustments, such as the subjective visual vertical, otolith input is integrated. We hypothesized that graviceptive input is incorporated when performing the LBT and predicted reduced accuracy and precision when roll-tilted. Twenty healthy right-handed subjects repetitively bisected Earth-horizontal and body-horizontal lines in darkness. Recordings were obtained before, during, and after roll-tilt (±45°, ±90°) for 5 min each. Additionally, bisections of Earth-vertical and oblique lines were obtained in 17 subjects. When roll-tilted ±90° ear-down, bisections of Earth-horizontal (i.e., body-vertical) lines were shifted toward the direction of the head (P < 0.001). However, after correction for vertical line-bisection errors when upright, shifts disappeared. Bisecting body-horizontal lines while roll-tilted did not cause any shifts. The precision of Earth-horizontal line bisections decreased (P ≤ 0.006) when roll-tilted, while no such changes were observed for body-horizontal lines. Regardless of the trial condition and paradigm, the scanning direction of the bisecting cursor (leftward vs. rightward) significantly (P ≤ 0.021) affected line bisections. Our findings reject our hypothesis and suggest that gravity does not modulate the LBT. Roll-tilt-dependent shifts are instead explained by the headward bias when bisecting lines oriented along a body-vertical axis. Increased variability when roll-tilted likely reflects larger variability when bisecting body-vertical than body-horizontal lines. Copyright © 2016 the American Physiological Society.

Strong rightward lateralization of the dorsal attentional network in left-handers with right sighting-eye: an evolutionary advantage.

PubMed

Petit, Laurent; Zago, Laure; Mellet, Emmanuel; Jobard, Gaël; Crivello, Fabrice; Joliot, Marc; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

2015-03-01

Hemispheric lateralization for spatial attention and its relationships with manual preference strength and eye preference were studied in a sample of 293 healthy individuals balanced for manual preference. Functional magnetic resonance imaging was used to map this large sample while performing visually guided saccadic eye movements. This activated a bilateral distributed cortico-subcortical network in which dorsal and ventral attentional/saccadic pathways elicited rightward asymmetrical activation depending on manual preference strength and sighting eye. While the ventral pathway showed a strong rightward asymmetry irrespective of both manual preference strength and eye preference, the dorsal frontoparietal network showed a robust rightward asymmetry in strongly left-handers, even more pronounced in left-handed subjects with a right sighting-eye. Our findings brings support to the hypothesis that the origin of the rightward hemispheric dominance for spatial attention may have a manipulo-spatial origin neither perceptual nor motor per se but rather reflecting a mechanism by which a spatial context is mapped onto the perceptual and motor activities, including the exploration of the spatial environment with eyes and hands. Within this context, strongly left-handers with a right sighting-eye may benefit from the advantage of having the same right hemispheric control of their dominant hand and visuospatial attention processing. We suggest that this phenomenon explains why left-handed right sighting-eye athletes can outperform their competitors in sporting duels and that the prehistoric and historical constancy of the left-handers ratio over the general population may relate in part on the hemispheric specialization of spatial attention. © 2014 Wiley Periodicals, Inc.

Line-Bisecting Performance in Highly Skilled Athletes: Does Preponderance of Rightward Error Reflect Unique Cortical Organization and Functioning?

ERIC Educational Resources Information Center

Carlstedt, Roland A.

2004-01-01

A line-bisecting test was administered to 250 highly skilled right-handed athletes and a control group of 60 right-handed age matched non-athletes. Results revealed that athletes made overwhelmingly more rightward errors than non-athletes, who predominantly bisected lines to the left of the veridical center. These findings were interpreted in the…

Prism adaptation and generalization during visually guided locomotor tasks.

PubMed

Alexander, M Scott; Flodin, Brent W G; Marigold, Daniel S

2011-08-01

The ability of individuals to adapt locomotion to constraints associated with the complex environments normally encountered in everyday life is paramount for survival. Here, we tested the ability of 24 healthy young adults to adapt to a rightward prism shift (∼11.3°) while either walking and stepping to targets (i.e., precision stepping task) or stepping over an obstacle (i.e., obstacle avoidance task). We subsequently tested for generalization to the other locomotor task. In the precision stepping task, we determined the lateral end-point error of foot placement from the targets. In the obstacle avoidance task, we determined toe clearance and lateral foot placement distance from the obstacle before and after stepping over the obstacle. We found large, rightward deviations in foot placement on initial exposure to prisms in both tasks. The majority of measures demonstrated adaptation over repeated trials, and adaptation rates were dependent mainly on the task. On removal of the prisms, we observed negative aftereffects for measures of both tasks. Additionally, we found a unilateral symmetric generalization pattern in that the left, but not the right, lower limb indicated generalization across the 2 locomotor tasks. These results indicate that the nervous system is capable of rapidly adapting to a visuomotor mismatch during visually demanding locomotor tasks and that the prism-induced adaptation can, at least partially, generalize across these tasks. The results also support the notion that the nervous system utilizes an internal model for the control of visually guided locomotion.

Differences in the Limits of Stability Between Older Rolling Walker Users and Older Single-Tip-Cane Users - A Preliminary Study.

PubMed

Liu, Hao Howe; Quiben, Myles; Holmes, Clayton; Connors, Michael; Salem, Yasser

To identify the differences in the limits of stability (LOS) between older rolling walker and single-tip-cane users. This was a matched paired t-test design with repeated measure. Eighteen older subjects were matched based on age, gender, and functional level. The subjects were assessed using the multidirectional reach test initially and 5-month later in four directions: forward, backward, leftward, and rightward. Initially, there were no differences between cane users and rolling walker users in the LOS in all directions. However, 5-month later, the cane users who held their canes in their right hand had significantly better stability in forward and rightward reach than the walker users (p < .05). Further, the walker users demonstrated significantly decreased functional reach in forward reach (p < .05). Cane users might have better stability than walker users in the forward direction and in the direction toward the side holding the cane. This study may provide guide for clinicians including nurses for selecting appropriate rehabilitative interventions for older adults using walkers and canes.

Prism adaptation does not alter object-based attention in healthy participants.

PubMed

Bultitude, Janet H; List, Alexandra; Aimola Davies, Anne M

2013-01-01

Hemispatial neglect ('neglect') is a disabling condition that can follow damage to the right side of the brain, in which patients show difficulty in responding to or orienting towards objects and events that occur on the left side of space. Symptoms of neglect can manifest in both space- and object-based frames of reference. Although patients can show a combination of these two forms of neglect, they are considered separable and have distinct neurological bases. In recent years considerable evidence has emerged to demonstrate that spatial symptoms of neglect can be reduced by an intervention called prism adaptation. Patients point towards objects viewed through prismatic lenses that shift the visual image to the right. Approximately five minutes of repeated pointing results in a leftward recalibration of pointing and improved performance on standard clinical tests for neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Here we examined the effect of prism adaptation on the performance of healthy participants who completed a computerised test of space- and object-based attention. Participants underwent adaptation to leftward- or rightward-shifting prisms, or performed neutral pointing according to a between-groups design. Significant pointing after-effects were found for both prism groups, indicating successful adaptation. In addition, the results of the computerised test revealed larger reaction-time costs associated with shifts of attention between two objects compared to shifts of attention within the same object, replicating previous work. However there were no differences in the performance of the three groups, indicating that prism adaptation did not influence space- or object-based attention for this task. When combined with existing literature, the results are consistent with the proposal that prism adaptation may only perturb cognitive functions for which normal baseline performance is already biased.

Prism adaptation does not alter object-based attention in healthy participants

PubMed Central

Bultitude, Janet H.

2013-01-01

Hemispatial neglect (‘neglect’) is a disabling condition that can follow damage to the right side of the brain, in which patients show difficulty in responding to or orienting towards objects and events that occur on the left side of space. Symptoms of neglect can manifest in both space- and object-based frames of reference. Although patients can show a combination of these two forms of neglect, they are considered separable and have distinct neurological bases. In recent years considerable evidence has emerged to demonstrate that spatial symptoms of neglect can be reduced by an intervention called prism adaptation. Patients point towards objects viewed through prismatic lenses that shift the visual image to the right. Approximately five minutes of repeated pointing results in a leftward recalibration of pointing and improved performance on standard clinical tests for neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Here we examined the effect of prism adaptation on the performance of healthy participants who completed a computerised test of space- and object-based attention. Participants underwent adaptation to leftward- or rightward-shifting prisms, or performed neutral pointing according to a between-groups design. Significant pointing after-effects were found for both prism groups, indicating successful adaptation. In addition, the results of the computerised test revealed larger reaction-time costs associated with shifts of attention between two objects compared to shifts of attention within the same object, replicating previous work. However there were no differences in the performance of the three groups, indicating that prism adaptation did not influence space- or object-based attention for this task. When combined with existing literature, the results are consistent with the proposal that prism adaptation may only perturb cognitive functions for which normal baseline performance is already biased. PMID:24715960

The effect of atrial pacing site on electrophysiological properties of the atrioventricular junction and induction of atrioventricular nodal reentry in patients with typical atrioventricular nodal reentrant tachycardia.

PubMed

Kiedrowicz, Radosław M; Kaźmierczak, Jarosław; Wielusiński, Maciej

2017-01-01

Clinical studies in humans have shown the site of atrial stimulation to influence atrioventricular (AV) conduction times and refractory periods, the demonstration of dual AV nodal (AVN) pathways, and induction of AVN reentry. These studies often found conflicting results. Moreover, among enrolled patients a minority of them were found to have AVN reentrant tachycardia (AVNRT). The purpose of this study was to investigate the effect of right and left atrial pacing on the electrophysiological properties of the AV junction in the typical AVNRT population. Ninety-two consecutive patients with typical AVNRT were included. Atrial pacing was performed from the high right atrium (HRA) and the left atrium via the proximal coronary sinus (CS). Stimulation from either the HRA or the CS could result in dual AVN physiology and AVNRT. No site-dependent differences in the ease of induction of dual AVN pathways with variability of initiation from either site were found. However, AVNRT was easier to induce from the HRA. With CS pacing the leftward but not the rightward AVN approaches were the entry point to the AV node because of significantly shorter AH conduction times compared to HRA pacing. Conduction over the leftward AVN extensions could initiate the tachycardia with significantly shorter critical AH interval compared to conduction over the rightward AVN extensions; however, the AH interval during AVNRT and its cycle length were not significantly different. Rightward and leftward AVN extensions are regular features of the AV node. Their different electrophysiological properties lead to variation in the demonstration of discontinuous AVN conduction and AVNRT during right and left atrial pacing. Despite the observation that the left AVN extensions could compose the entry point to the reentrant circuit, there is no evidence that they constitute the critical component of sustained typical AVNRT.

Changes in Brain Lateralization in Patients with Mild Cognitive Impairment and Alzheimer's Disease: A Resting-State Functional Magnetic Resonance Study from Alzheimer's Disease Neuroimaging Initiative.

PubMed

Liu, Hao; Zhang, Lele; Xi, Qian; Zhao, Xiaohu; Wang, Fei; Wang, Xiangbin; Men, Weiwei; Lin, Qixiang

2018-01-01

To detect changes in brain lateralization in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using resting-state functional magnetic resonance imaging (fMRI). Data from 61 well-matched right-handed subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative, including 19 healthy controls (HCs), 25 patients with MCI, and 17 patients with AD. First, we divided 256 pairs of seed regions from each hemisphere covering the entire cerebral gray matter. Then, we used the intrinsic laterality index (iLI) approach to quantify the functional laterality using fMRI. One-way ANOVA was employed to estimate the differences in iLI among the three groups. The sum, number and mean value of the iLI were calculated within the thresholds of 0 < |iLI| < 0.2, 0.2 ≤ |iLI| < 0.4, 0.4 ≤ |iLI| < 0.8, and |iLI| ≥ 0.8, to explore the changes in the lateralization of resting-state brain function in patients with MCI and AD. One-way ANOVA revealed that the iLIs of the three groups were significantly different. The HCs showed a significant leftward interhemispheric difference within |iLI| ≥ 0.8. Compared with the HCs, the patients with MCI manifested a distinct abnormal rightward interhemispheric asymmetry, mainly within the thresholds of 0.2 ≤ |iLI| < 0.4 and 0.4 ≤ |iLI| < 0.8; in the patients with AD, the normal leftward lateralization that was observed in the HCs disappeared, and an abnormal rightward laterality was expressed within 0.4 ≤ |iLI| < 0.8. By directly comparing the patients with MCI with the patients with AD, an exclusive abnormal rightward laterality was observed in the patients with MCI within the 0.2 ≤ |iLI| < 0.4 threshold, and the normal leftward asymmetry vanished in the patients with AD within the |iLI| ≥ 0.8 threshold. Global brain lateralization was different among three groups. The abnormal rightward dominance observed in the patients with MCI and AD may indicate that these patients use additional brain resources to compensate for the loss of cognitive function, and the observed disappearance of the leftward laterality in the patients with AD was likely associated with the damage in the left hemisphere. The observed disappearance of the rightward asymmetry in the patients with AD using the 0.2 ≤ |iLI| < 0.4 threshold was likely a sign of decompensation. Our study provides new insights that may improve our understanding of MCI and AD.

Development and clinical application of a computer-aided real-time feedback system for detecting in-bed physical activities.

PubMed

Lu, Liang-Hsuan; Chiang, Shang-Lin; Wei, Shun-Hwa; Lin, Chueh-Ho; Sung, Wen-Hsu

2017-08-01

Being bedridden long-term can cause deterioration in patients' physiological function and performance, limiting daily activities and increasing the incidence of falls and other accidental injuries. Little research has been carried out in designing effective detecting systems to monitor the posture and status of bedridden patients and to provide accurate real-time feedback on posture. The purposes of this research were to develop a computer-aided system for real-time detection of physical activities in bed and to validate the system's validity and test-retest reliability in determining eight postures: motion leftward/rightward, turning over leftward/rightward, getting up leftward/rightward, and getting off the bed leftward/rightward. The in-bed physical activity detecting system consists mainly of a clinical sickbed, signal amplifier, a data acquisition (DAQ) system, and operating software for computing and determining postural changes associated with four load cell sensing components. Thirty healthy subjects (15 males and 15 females, mean age = 27.8 ± 5.3 years) participated in the study. All subjects were asked to execute eight in-bed activities in a random order and to participate in an evaluation of the test-retest reliability of the results 14 days later. Spearman's rank correlation coefficient was used to compare the system's determinations of postural states with researchers' recordings of postural changes. The test-retest reliability of the system's ability to determine postures was analyzed using the interclass correlation coefficient ICC(3,1). The system was found to exhibit high validity and accuracy (r = 0.928, p < 0.001; accuracy rate: 87.9%) in determining in-bed displacement, turning over, sitting up, and getting off the bed. The system was particularly accurate in detecting motion rightward (90%), turning over leftward (83%), sitting up leftward or rightward (87-93%), and getting off the bed (100%). The test-retest reliability ICC(3,1) value was 0.968 (p < 0.001). The system developed in this study exhibits satisfactory validity and reliability in detecting changes in-bed body postures and can be beneficial in assisting caregivers and clinical nursing staff in detecting the in-bed physical activities of bedridden patients and in developing fall prevention warning systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Hand preference and skilled hand performance among individuals with successful rightward conversions of the writing hand.

PubMed

Porac, Clare

2009-03-01

Searleman and Porac (2001) studied lateral preference patterns among successfully switched left-hand writers, left-hand writers with no switch pressure history, and left-hand writers who did not switch when pressured. They concluded that left-handers who successfully shift to right-hand writing are following an inherent right-sided lateralisation pattern that they already possess. Searleman and Porac suggested that the neural mechanisms that control lateralisation in the successfully switched individuals are systematically different from those of other groups of left-handers. I examined patterns of skilled and less-skilled hand preference and skilled hand performance in a sample of 394 adults (ages 18-94 years). The sample contained successfully switched left-hand writers, left-handers pressured to shift who remained left-hand writers, left-handers who did not experience shift pressures, and right-handers. Both skilled hand preference and skilled hand performance were shifted towards the right side in successfully switched left-hand writers. This group also displayed mixed patterns of hand preference and skilled hand performance in that they were not as right-sided as "natural" right-handers nor were they as left-sided as the two left-hand writing groups, which did not differ from each other. The experience of being pressured to switch to right-hand writing was not sufficient to shift lateralisation patterns; the pressures must be experienced in the context of an underlying neural control mechanism that is amenable to change as a result of these external influences.

Apparent Affinity Estimates and Reversal of the Effects of Synthetic Cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by Rimonabant in Rhesus Monkeys.

PubMed

Hruba, Lenka; McMahon, Lance R

2017-08-01

Synthetic cannabinoids have been prohibited due to abuse liability and toxicity. Four such synthetic cannabinoids, AM-2201 ([1-(5-fluoropentyl)indol-3-yl]-naphthalen-1-ylmethanone), CP-47,497 (2-[(1R,3S)-3-hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenol), JWH-122 [(4-methylnaphthalen-1-yl)-(1-pentylindol-3-yl)methanone], and JWH-250 [2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone], were tested for their capacity to produce CB 1 receptor-mediated discriminative stimulus effects in two groups of rhesus monkeys. One group ( n = 4) discriminated Δ 9 -tetrahydrocannabinol (∆ 9 -THC; 0.1 mg/kg i.v.), and a second group ( n = 4) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving 1 mg/kg/12 hours of ∆ 9 -THC. AM-2201, JWH-122, CP-47,497, JWH-250, and ∆ 9 -THC increased ∆ 9 -THC lever responding. Duration of action was 1-2 hours for AM-2201, JWH-122, and JWH-250 and 4-5 hours for CP-47,497 and ∆ 9 -THC. Rimonabant (1 mg/kg) surmountably antagonized the discriminative stimulus effects of all cannabinoid agonists; the magnitude of rightward shift was 10.6-fold for AM-2201, 10.7-fold for JWH-122, 11.0-fold for CP-47,497, and 15.7-fold for JWH-250. The respective pK B values were not significantly different: 6.61, 6.65, 6.66, and 6.83. In ∆ 9 -THC-treated monkeys discriminating rimonabant, AM-2201 (0.1 and 0.32 mg/kg), JWH-122 (0.32 and 1 mg/kg), JWH-250 (1 and 3.2 mg/kg), and CP-47,497 (0.32, 1, and 3.2 mg/kg) produced not only rate-decreasing effects that were reversed by rimonabant, but also dose-dependent, rightward shifts in the rimonabant discrimination dose-effect function. These results show striking similarity in the CB 1 receptor mechanism mediating the subjective effects of AM-2201, JWH-122, JWH-250, and CP-47,497. For products containing AM-2201 and JWH-122, a short duration of action could lead to more frequent use; moreover, inattention to differences in potency among synthetic cannabinoids could underlie unexpected toxicity. Rapid reversal of effects by intravenous rimonabant has potential value in emergency situations. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Sex- and age-related differences in the chronic pressure-natriuresis relationship: role of the angiotensin type 2 receptor.

PubMed

Mirabito, Katrina M; Hilliard, Lucinda M; Kett, Michelle M; Brown, Russell D; Booth, Sean C; Widdop, Robert E; Moritz, Karen M; Evans, Roger G; Denton, Kate M

2014-10-15

Sex hormones regulate the renin-angiotensin system. For example, estrogen enhances expression of the angiotensin type 2 receptor. We hypothesized that activation of the angiotensin type 2 receptor shifts the chronic pressure-natriuresis relationship leftward in females compared with males and that this effect is lost with age. Mean arterial pressure was measured by radiotelemetry in adult (4 mo old) and aged (14 mo old) wild-type and angiotensin type 2 receptor knockout male and female mice. Chronic pressure-natriuresis curves were constructed while mice were maintained on a normal-salt (0.26%) diet and following 6 days of high salt (5.0%) diet. Mean arterial pressure was lower in adult wild-type females than males (88 ± 1 and 97 ± 1 mmHg, respectively), a difference that was maintained with age, but was absent in adult knockout mice. In wild-type females, the chronic pressure-natriuresis relationship was shifted leftward compared with knockout females, an effect that was lost with age. In males, the chronic pressure-natriuresis relationship was not influenced by angiotensin type 2 receptor deficiency. Compared with age-matched females, the chronic pressure-natriuresis relationships in male mice were shifted rightward. Renal expression of the angiotensin type 2 receptor was fourfold greater in adult wild-type females than males. With age, the angiotensin type 2 receptor-to-angiotensin type 1 receptor balance was reduced in females. Conversely, in males, angiotensin receptor expression did not vary significantly with age. In conclusion, the angiotensin type 2 receptor modulates the chronic pressure-natriuresis relationship in an age- and sex-dependent manner. Copyright © 2014 the American Physiological Society.

Contrast of Hemispheric Lateralization for Oro-Facial Movements between Learned Attention-Getting Sounds and Species-Typical Vocalizations in Chimpanzees: Extension in a Second Colony

ERIC Educational Resources Information Center

Wallez, Catherine; Schaeffer, Jennifer; Meguerditchian, Adrien; Vauclair, Jacques; Schapiro, Steven J.; Hopkins, William D.

2012-01-01

Studies involving oro-facial asymmetries in nonhuman primates have largely demonstrated a right hemispheric dominance for communicative signals and conveyance of emotional information. A recent study on chimpanzee reported the first evidence of significant left-hemispheric dominance when using attention-getting sounds and rightward bias for…

Stuttering as a trait or state - an ALE meta-analysis of neuroimaging studies.

PubMed

Belyk, Michel; Kraft, Shelly Jo; Brown, Steven

2015-01-01

Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimaging studies of persistent developmental stuttering. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles.

PubMed

de Godoy, Márcio Augusto Fressatto; Accorsi-Mendonça, Daniela; de Oliveira, Ana Maria

2003-02-01

We have evaluated the interaction between angiotensin II (Ang II) and the cholinergic transmission in anococcygeus smooth muscles isolated from rats treated (sympathectomised group) or not (vehicle group) with reserpine and alpha-methyl-p-tyrosine. For this, we contracted the tissues with Ang II in the presence and absence of atropine and hexamethonium. Ang II induced concentration-dependent contractions, which did not undergo temporal changes in tissues isolated from both groups of rats. In the vehicle group, Ang II induced more potent contractions than in the sympathectomised group. In the sympathectomised rat group, atropine inhibited the contractions induced by Ang II in a concentration-dependent fashion with no decrease in E(max). Additionally, hexamethonium inhibited the contraction induced by Ang II in a concentration-dependent fashion with a decrease in E(max). Association of atropine and hexamethonium produced Ang II-induced curves with rightward shifts from the control curve with a decrease in E(max). Incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) reversed the effects of atropine and hexamethonium association. Conversely, in the vehicle group of rats, atropine and hexamethonium did not produce any significant effect. However, in the presence of yohimbine, atropine shifted the Ang II-induced curves to the right of the control curve with no E(max) decrease. Results suggest that there is a positive interaction between Ang II and cholinergic transmission in the rat anococcygeus smooth muscle mediated by angiotensin receptors located on pre-ganglionic cells.

Myofilament properties comprise the rate-limiting step for cardiac relaxation at body temperature in the rat.

PubMed

Janssen, Paul M L; Stull, Linda B; Marbán, Eduardo

2002-02-01

The majority of studies aimed at characterizing basic contractile mechanisms have been conducted at room temperature. To elucidate the mechanism of cardiac relaxation under more physiological conditions, we investigated contractile function and calcium handling in ultrathin rat cardiac trabeculae. Active developed tension was unaltered between 22.5 and 30.0 degrees C (from 89 +/- 10 to 86 +/- 11 mN/mm(2), P = not significant) but steeply declined at 37.5 degrees C (30 +/- 5 mN/mm(2)). Meanwhile, the speed of relaxation (time from peak force to 50% relaxation) declined from 22.5 to 30.0 degrees C (from 360 +/- 40 to 157 +/- 17 ms) and further declined at 37.5 degrees C to 76 +/- 13 ms. Phase-plane analysis of calcium versus force revealed that, with increasing temperature, the relaxation phase is shifted rightward, indicating that the rate-limiting step of relaxation tends to depend more on calcium kinetics as temperature rises. The force-frequency relationship, which was slightly negative at 22.5 degrees C (0.1 vs. 1 Hz: 77 +/- 12 vs. 66 +/- 7 mN/mm(2)), became clearly positive at 37.5 degrees C (1 vs. 10 Hz: 30 +/- 5 vs. 69 +/- 9 mN/mm(2)). Phase-plane analyses indicated that, with increasing frequency, the relaxation phase is shifted leftward. We conclude that temperature independently affects contraction and relaxation, and cross-bridge cycling kinetics become rate limiting for cardiac relaxation under experimental conditions closest to those in vivo.

The effect of isoenzyme-selective PDE inhibitors on methacholine-induced contraction of guinea-pig and rat ileum.

PubMed Central

Tomkinson, A.; Raeburn, D.

1996-01-01

1. We have examined the effects of the isoenzyme-selective phosphodiesterase (PDE) inhibitors, vinpocetine (type 1), siguazodan (type 3), rolipram (type 4) and zaprinast (type 5) and the non-selective PDE inhibitor enprofylline on methacholine (MCh) contractile concentration-response curves on guinea-pig and rat isolated ileum. 2. In guinea-pig ileum, vinpocetine (10-300 microM), zaprinast (1-300 microM) and enprofylline (100-1000 microM) produced a concentration-dependent depression of the maximum response (Emax) to MCh only without effect on the MCh EC50 values (rank order of potency: zaprinast > vinpocetine > enprofylline). In contrast, siguazodan (10-300 microM) and rolipram (10-300 microM) produced a rightward displacement of the MCh concentration-response curve (increase in EC50: rank order; rolipram > siguazodan), with effects on the MCh maximum seen only at higher concentrations. 3. In the rat ileum, vinpocetine (10-300 microM), zaprinast (0.1-300 microM) and enprofylline (100-1000 microM) caused depression of the MCh maximum contraction (rank order: zaprinast > vinpocetine > enprofylline). Low concentrations of rolipram and siguazodan had no significant effect on the MCh maximum. In the presence of higher concentrations (> 100 microM) of rolipram and siguazodan, a maximum response was not achieved at the highest concentration of MCh tested. As in the guinea-pig ileum, only rolipram (10-300 microM) and siguazodan (10-300 microM) produced a significant, concentration-dependent, rightward displacement of the MCh concentration-response curve (increase in EC50: rank order: rolipram > siguazodan). 4. In the guinea-pig ileum, isoprenaline (0.1 microM) produced a rightward displacement (approximately 3 fold) of the MCh concentration-response curve, accompanied by a significant depression of the maximum response. Increasing the isoprenaline concentration (1 microM) had no further effect on either parameter. Sodium nitroprusside (SNP, > or = 10 microM) produced a concentration-dependent depression of the MCh maximum without an effect on the EC50. 5. In the rat ileum, isoprenaline (1 microM) produced a concentration-dependent rightward displacement (approximately 2.8 fold) of the MCh concentration-response curve with depression of the MCh maximum at higher (> or = 100 microM) concentrations. SNP produced depression of the MCh maximum at a concentration of 10 microM and above. Effects on the MCh EC50 were seen only at 100 and 300 microM. 6. In guinea-pig ileum, isoprenaline (0.1 microM) in combination with rolipram (10 microM) further increased the MCh EC50 and reduced the MCh maximum. The combination of SNP (10 microM) with zaprinast (0.1 microM) produced no further significant effect than SNP alone. 7. In rat ileum, isoprenaline (1 microM) in combination with rolipram (10 microM) further increased the EC50 and reduced the maximum. SNP (10 microM) had no significant effect on either the MCh maximum or EC50. A combination with zaprinast (1 microM) had no further effect. 8. In conclusion, all the PDE inhibitors tested produced a concentration-dependent inhibition of the MCh concentration-response curve, indicating a modulator role for the PDE isoenzymes in gastrointestinal smooth muscle contractility. The PDE inhibitors that elevate cyclic GMP produced a depression of the MCh maximum response only, whilst those that elevate cyclic AMP produced a rightward displacement of the MCh concentration-response curve. This was confirmed by the use of isoprenaline and SNP. This difference in the type of inhibition produced by these PDE isoenzyme inhibitors may reflect a different intracellular site/mechanism by which the cyclic AMP- and cyclic GMP-activated kinases act functionally to antagonize the contractile response. PMID:8864552

Combining language and space: sentence bisection in unilateral spatial neglect.

PubMed

Veronelli, Laura; Guasti, Maria T; Arduino, Lisa S; Vallar, Giuseppe

2014-10-01

In line bisection right-brain-damaged patients with left spatial neglect show a rightward deviation, with respect to the line's physical center. In word bisection ortho-phonological features of the stimulus' final (right-sided) part modulate performance of both patients and healthy participants (Veronelli, Vallar, Marinelli, Primativo, & Arduino, 2014). We investigated the role of linguistic factors in sentence bisection, in patients with and without neglect, and control participants. The effects of information in the right-sided part of the sentence (Experiment #1), and of lexical and syntactic violations (Experiment #2) were assessed. Neglect patients showed an overall rightward bias, larger than those of patients without neglect and controls. The neglect patients' bias was modulated by stimulus type, decreasing from lines, to letter strings and to all types of sentences. In sum, in visuo-manual sentence bisection a basic linguistic mechanism, such as sentence readability, brings about a more leftward appreciation of the stimulus, reducing the neglect patients' rightward bias. Copyright © 2014 Elsevier Inc. All rights reserved.

Evolution of the strongest vertebrate rightward action asymmetries: Marine mammal sidedness and human handedness.

PubMed

MacNeilage, Peter F

2014-03-01

Marine mammals and humans have the strongest manifestations of what is apparently a vertebrate-wide tendency toward a rightward action asymmetry associated with routine behavior. Marine mammal asymmetries usually involve whole-body actions associated with feeding. The human-like strength of these asymmetries may result from a problem of external aquatic support for the reactive component of the demanding lateral maneuvers of large marine mammals in daily pursuit of prey. Our asymmetrical primate heritage may also have begun with a rightward whole-body asymmetry, in prosimians, perhaps also resulting from problems of support for the reactive component of action; in this case arising from the arboreal habitat (and paradoxically including left-handedness). Monkeys and apes (simians) subsequently added right-sided adaptations for manipulation, bimanual coordination, bipedalism, throwing, and manual communication, most importantly by distal elaboration of limb function. The strength of human right-handedness may result partly from further elaboration of these simian action adaptations and partly from an evolving cognitive superstructure for tool use and language.

Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe.

PubMed

Bonow, R O; Ostrow, H G; Rosing, D R; Cannon, R O; Lipson, L C; Maron, B J; Kent, K M; Bacharach, S L; Green, M V

1983-11-01

To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.

Butylidenephthalide blocks potassium channels and enhances basal tension in isolated guinea-pig trachea.

PubMed

Hsu, Hsin-Te; Yang, You-Lan; Chen, Wan-Chen; Chen, Chi-Ming; Ko, Wun-Chang

2014-01-01

Butylidenephthalide (Bdph, 30~300 μM), a constituent of Ligusticum chuanxiong Hort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 μM), and its tension changes were isometrically recorded. Cromakalim (3 μM), an ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 μM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 μM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 μM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 μM) and 4-aminopiridine (4-AP, 5 mM), a blocker of K v 1 family of K+ channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of K v 1 family of K+ channels, to enhance the baseline tension of guinea-pig trachea.

Prism adaptation does not alter configural processing of faces

PubMed Central

Bultitude, Janet H.; Downing, Paul E.; Rafal, Robert D.

2013-01-01

Patients with hemispatial neglect (‘neglect’) following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non-lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects of prism adaptation are limited to dorsal stream processing. PMID:25110574

Prism adaptation does not alter configural processing of faces.

PubMed

Bultitude, Janet H; Downing, Paul E; Rafal, Robert D

2013-01-01

Patients with hemispatial neglect ('neglect') following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non-lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects of prism adaptation are limited to dorsal stream processing.

Rightward dominance in temporal high-frequency electrical asymmetry corresponds to higher resting heart rate and lower baroreflex sensitivity in a heterogeneous population.

PubMed

Tegeler, Charles H; Shaltout, Hossam A; Tegeler, Catherine L; Gerdes, Lee; Lee, Sung W

2015-06-01

Explore potential use of a temporal lobe electrical asymmetry score to discriminate between sympathetic and parasympathetic tendencies in autonomic cardiovascular regulation. 131 individuals (82 women, mean age 43.1, range 13-83) with diverse clinical conditions completed inventories for depressive (CES-D or BDI-II) and insomnia-related (ISI) symptomatology, and underwent five-minute recordings of heart rate and blood pressure, allowing calculation of heart rate variability and baroreflex sensitivity (BRS), followed by one-minute, two-channel, eyes-closed scalp recordings of brain electrical activity. A temporal lobe high-frequency (23-36 Hz) electrical asymmetry score was calculated for each subject by subtracting the average amplitude in the left temporal region from amplitude in the right temporal region, and dividing by the lesser of the two. Depressive and insomnia-related symptomatology exceeding clinical threshold levels were reported by 48% and 50% of subjects, respectively. Using a cutoff value of 5% or greater to define temporal high-frequency asymmetry, subjects with leftward compared to rightward asymmetry were more likely to report use of a sedative-hypnotic medication (42% vs. 22%, P = 0.02). Among subjects with asymmetry of 5% or greater to 30% or greater, those with rightward compared to leftward temporal high-frequency asymmetry had higher resting heart rate (≥5% asymmetry, 72.3 vs. 63.8, P = 0.004; ≥10%, 71.5 vs. 63.0, P = 0.01; ≥20%, 72.2 vs. 64.2, P = 0.05; ≥30%, 71.4 vs. 64.6, P = 0.05). Subjects with larger degrees of rightward compared to leftward temporal high-frequency asymmetry had lower baroreflex sensitivity (≥40% asymmetry, 10.6 vs. 16.4, P = 0.03; ≥50% asymmetry, 10.4 vs. 16.7, P = 0.05). In a heterogeneous population, individuals with rightward compared to leftward temporal high-frequency electrical asymmetry had higher resting heart rate and lower BRS. Two-channel recording of brain electrical activity from bilateral temporal regions appears to hold promise for further investigation as a means to assess cortical activity associated with autonomic cardiovascular regulation.

An online means of testing asymmetries in seating preference reveals a bias for airplanes and theaters.

PubMed

Nicholls, Michael E R; Thomas, Nicole A; Loetscher, Tobias

2013-08-01

The aim of this study was to investigate asymmetrical interactions between humans and their environment using online seat booking sites. Functional differences between the cerebral hemispheres affect the choices people make. For example, when asked to imagine going to a cinema, people preferentially select seats to the right We investigated whether this experimental research generalizes to online booking sites for aircraft and theaters. Occupancy rates for seats taken on the left and right sides were assessed for 100 airline flights with 12,762 available seats and 37 theater performances with 34,456 seats. On the basis of previous research, a rightward bias was predicted for aircraft and theaters. For aircraft, contrary to expectation, occupancy rate was higher for left- compared with right-side seats. For theaters, a rightward bias was observed when the theater was less than half full.The bias was not affected by the orientation of the map. For aircraft, the leftward preference could be attributable to a rightward turning bias or a "feeling" that the port seats are closer to the exit, even though they are not. For theaters, the data demonstrate that the rightward preference observed in earlier studies exists only when the theater is relatively empty. Asymmetrical seating may play an important role in the efficient assimilation of information from the environment, and this role should take this into account when designing effective human-environment interfaces.The online method of assessing seating used in the current study provides an informative and potentially powerful means of assessing asymmetries in human perception and action.

[Intrathoracic movement of the normal and hypertrophied hearts measured by biplane coronary cineangiography].

PubMed

Osato, S; Ishikawa, K; Kanamasa, K; Ogai, T; Oda, A; Katori, R

1984-06-01

The shift of the heart during systole within the thorax was measured using bifurcations of the left coronary artery as cineangiographic markers. Biplane coronary cineangiography was performed in 13 normal subjects and 6 patients with non-obstructive hypertrophic cardiomyopathy (HCM). The spatial coordinates (X, Y, Z) of the bifurcations on the cineangiograms were measured using a motion analizer-digitizer-computer system. The systolic excursion of the motion of a bifurcation located at the anterior-basal point of the heart was 1.4 +/- 0.1 (+/-SD) cm leftward, 3.0 +/- 0.3 cm caudally and 2.5 +/- 0.1 cm anteriorly in normal subjects. In the cases with HCM, on the other hand, the bifurcation moved 2.2 +/- 1.1, 2.7 +/- 1.2 and 2.2 +/- 0.6 cm during systole, respectively. The movement at the apex in the normal subjects was 1.7 +/- 0.2 cm rightward, 1.5 +/- 0.2 cm caudally and 1.5 +/- 0.2 cm posteriorly, although the direction was reversed as compared to that of the anterior wall of the cardiac base. The amplitude of the excursion was also reduced at the apex, suggesting the systolic twist of the ventricular wall. The excursion of the apex in HCM was 0.6 +/- 1.7, 1.5 +/- 1.8 and 2.5 +/- 1.4 cm, respectively, toward the base of the heart as in the normal subjects. The maximum speeds of these motions were 34.0 +/- 9.2 cm/sec leftward, caudally and anteriory at the anterior-basal point and 36.2 +/- 7.3 cm/sec rightward, caudally and posteriorly in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Militarized humanitarianism meets carceral feminism: the politics of sex, rights, and freedom in contemporary antitrafficking campaigns.

PubMed

Bernstein, Elizabeth

2010-01-01

Over the past decade, abolitionist feminist and evangelical Christian activists have directed increasing attention toward the “traffic in women” as a dangerous manifestation of global gender inequalities. Despite renowned disagreements around the politics of sex and gender, these groups have come together to advocate for harsher penalties against traffickers, prostitutes’ customers, and nations deemed to be taking insufficient steps to stem the flow of trafficked women. In this essay, I argue that what has served to unite this coalition of "strange bedfellows" is not simply an underlying commitment to conservative ideals of sexuality, as previous commentators have offered, but an equally significant commitment to carceral paradigms of justice and to militarized humanitarianism as the preeminent mode of engagement by the state. I draw upon my ongoing ethnographic research with feminist and evangelical antitrafficking movement leaders to argue that the alliance that has been so efficacious in framing contemporary antitrafficking politics is the product of two historically unique and intersecting trends: a rightward shift on the part of many mainstream feminists and other secular liberals away from a redistributive model of justice and toward a politics of incarceration, coincident with a leftward sweep on the part of many younger evangelicals toward a globally oriented social justice theology. In the final section of this essay, I consider the resilience of these trends given a newly installed and more progressive Obama administration, positing that they are likely to continue even as the terrain of militarized humanitarian action shifts in accordance with new sets of geopolitical interests.

Inflammation Subverts Hippocampal Synaptic Plasticity in Experimental Multiple Sclerosis

PubMed Central

Mandolesi, Georgia; Piccinin, Sonia; Berretta, Nicola; Pignatelli, Marco; Feligioni, Marco; Musella, Alessandra; Gentile, Antonietta; Mori, Francesco; Bernardi, Giorgio; Nicoletti, Ferdinando; Mercuri, Nicola B.; Centonze, Diego

2013-01-01

Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency–synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS. PMID:23355887

Long-term physiological effects of enhanced O/sub 2/ release by inositol hexaphosphate-loaded erythrocytes

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

Teisseire, B.; Ropars, C.; Villereal, M.C.

1987-10-01

A continuous lysing and resealing procedure with erythrocytes permitted incorporation in these cells of inositol hexaphosphate (InsP/sub 6/), a strong allosteric effector of Hb. This leads to significant rightward shifts of the HbO/sub 2/ dissociation curves with in vitro P/sub 50/, values increasing from 32.2 +/- 1.8 torr for control erythrocytes to 86 +/- 60 torr. The shape of the dissociation curve was still sigmoidal, although the Hill coefficient was decreased. The life span of InsP/sub 6/-loaded erythrocytes equaled that of control erythrocytes. Erythrocyte-survival studies were done using /sub 51/Cr labeling of cells. The long-term physiological effects of the InsP/submore » 6/-loaded erythrocytes on piglets were increased O/sub 2/ release and reduced cardiac output. The reduced O/sub 2/ affinity of the InsP/sub 6/-loaded erythrocytes was still effective 20 days after transfusion in awake piglets. The electrolyte concentration appeared stable over the 5-day observation period except for a transient, but significant, hyperkalemia immediately after transfusion. The reductions in the O/sub 2/ affinity of Hb reported here are large compared with previously reported values. Introduction of InsP/sub 6/ into viable erythrocytes improves tissue oxygenation when, for any reason, normal blood flow is impaired.« less

Wandering spleen, gastric and pancreatic volvulus and right-sided descending and sigmoid colon.

PubMed

Flores-Ríos, Enrique; Méndez-Díaz, Cristina; Rodríguez-García, Esther; Pérez-Ramos, Tania

2015-10-01

Wandering spleen is a rare condition, characterized by a mobile spleen that is attached only by an elongated vascular pedicle, allowing it to migrate to any part of the abdomen or pelvis. Mesenteroaxial gastric volvulus usually occurs in children and may be associated with wandering spleen. Both entities result from abnormal laxity or absence of the peritoneal attachments due to abnormal fusion of the peritoneal mesenteries. Pancreatic volvulus is a very rare anomaly, with only a few isolated case reports described in association with wandering spleen. Anomalous right sided descending and sigmoid colon is a very rare entity and its association with wandering spleen has not been previously reported. We report a case of wandering spleen associated with mesenteroaxial gastric volvulus, pancreatic volvulus and rightward shift of the splenic flexure of the colon and right sided descending and sigmoid colon in a young female.

Wandering spleen, gastric and pancreatic volvulus and right-sided descending and sigmoid colon

PubMed Central

Flores-Ríos, Enrique; Méndez-Díaz, Cristina; Rodríguez-García, Esther; Pérez-Ramos, Tania

2015-01-01

Wandering spleen is a rare condition, characterized by a mobile spleen that is attached only by an elongated vascular pedicle, allowing it to migrate to any part of the abdomen or pelvis. Mesenteroaxial gastric volvulus usually occurs in children and may be associated with wandering spleen. Both entities result from abnormal laxity or absence of the peritoneal attachments due to abnormal fusion of the peritoneal mesenteries. Pancreatic volvulus is a very rare anomaly, with only a few isolated case reports described in association with wandering spleen. Anomalous right sided descending and sigmoid colon is a very rare entity and its association with wandering spleen has not been previously reported. We report a case of wandering spleen associated with mesenteroaxial gastric volvulus, pancreatic volvulus and rightward shift of the splenic flexure of the colon and right sided descending and sigmoid colon in a young female. PMID:26629290

Regulation of hematopoiesis in rats exposed to antiorthostatic, hypokinetic/hypodynamia. I - Model description

NASA Technical Reports Server (NTRS)

Dunn, C. D. R.; Johnson, P. C.; Lange, R. D.; Perez, L.; Nessel, R.

1985-01-01

The effect of a 7-day suspension in a jacket and harness with 20-deg head-down tilt on body weight, food and water consumption, and hematological parameters is investigated experimentally in male Sprague-Dawley rats weighing 150-175 g. The results are presented in graphs and compared with those for unsuspended controls and with published data on rats and humans exposed to microgravity in space flight. Suspended rats are found to have reduced red-blood-cell mass, erythropoiesis, plasma volume (leading to temporarily increased hematocrit), body weight, and food and water consumption; rightward-shifted oxyhemoglobin-dissociation curves; and unchanged platelet count, leucocyte count or PHA reactivity, and red-blood-cell shape distribution. Since many of these effects are also seen in space flight, the present experimental model is considered a promising technique for simulating the hematopoietic effects of microgravity at 1 g.

Combined organizational and activational effects of short and long photoperiods on spatial and temporal memory in rats.

PubMed

MacDonald, Christopher J; Cheng, Ruey-Kuang; Williams, Christina L; Meck, Warren H

2007-02-22

The present study examined the effects of photoperiod on spatial and temporal memory in adult Sprague-Dawley rats that were conceived and reared in different day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8 light/dark). Both male and female LD rats demonstrated increased spatial memory capacity as evidenced by a lower number of choices to criterion in a 12-arm radial maze task relative to the performance of SD rats. SD rats also demonstrated a distortion in the content of temporal memory as evidenced by a proportional rightward shift in the 20 and 60 s temporal criteria trained using the peak-interval procedure that is consistent with reduced cholinergic function. The conclusion is that both spatial and temporal memory are sensitive to photoperiod variation in laboratory rats in a manner similar to that previously observed for reproductive behaviour.

Influence of cigarette smoking on human autonomic function

NASA Technical Reports Server (NTRS)

Niedermaier, O. N.; Smith, M. L.; Beightol, L. A.; Zukowska-Grojec, Z.; Goldstein, D. S.; Eckberg, D. L.

1993-01-01

BACKGROUND. Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS. We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS. In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

Effects of prior short multiple-sprint exercises with different intersprint recoveries on the slow component of oxygen uptake during high-intensity exercise.

PubMed

Lanzi, Stefano; Borrani, Fabio; Wolf, Martin; Gojanovic, Boris; Malatesta, Davide

2012-12-01

This study compares the effects of two short multiple-sprint exercise (MSE) (6 × 6 s) sessions with two different recovery durations (30 s or 180 s) on the slow component of oxygen uptake ([Formula: see text]O(2)) during subsequent high-intensity exercise. Ten male subjects performed a 6-min cycling test at 50% of the difference between the gas exchange threshold and [Formula: see text]O(2peak) (Δ50). Then, the subjects performed two MSEs of 6 × 6 s separated by two intersprint recoveries of 30 s (MSE(30)) and 180 s (MSE(180)), followed 10 min later by the Δ50 (Δ50(30) and Δ50(180), respectively). Electromyography (EMG) activities of the vastus medialis and lateralis were measured throughout each exercise bout. During MSE(30), muscle activity (root mean square) increased significantly (p ≤ 0.04), with a significant leftward-shifted median frequency of the power density spectrum (MDF; p ≤ 0.01), whereas MDF was significantly rightward-shifted during MSE(180) (p = 0.02). The mean [Formula: see text]O(2) value was significantly higher in MSE(30) than in MSE(180) (p < 0.001). During Δ50(30), [Formula: see text]O(2) and the deoxygenated hemoglobin ([HHb]) slow components were significantly reduced (-27%, p = 0.02, and -34%, p = 0.003, respectively) compared with Δ50. There were no significant modifications of the [Formula: see text]O(2) slow component in Δ50(180) compared with Δ50 (p = 0.32). The neuromuscular and metabolic adaptations during MSE(30) (preferential activation of type I muscle fibers evidenced by decreased MDF and a greater aerobic metabolism contribution to the required energy demands), but not during MSE(180), may lead to reduced [Formula: see text]O(2) and [HHb] slow components, suggesting an alteration in motor units recruitment profile (i.e., change in the type of muscle fibers recruited) and (or) an improved muscle O(2) delivery during subsequent exercise.

The lighter side of advertising: investigating posing and lighting biases.

PubMed

Thomas, Nicole A; Burkitt, Jennifer A; Patrick, Regan E; Elias, Lorin J

2008-11-01

People tend to display the left cheek when posing for a portrait; however, this effect does not appear to generalise to advertising. The amount of body visible in the image and the sex of the poser might also contribute to the posing bias. Portraits also exhibit lateral lighting biases, with most images being lit from the left. This effect might also be present in advertisements. A total of 2801 full-page advertisements were sampled and coded for posing direction, lighting direction, sex of model, and amount of body showing. Images of females showed an overall leftward posing bias, but the biases in males depended on the amount of body visible. Males demonstrated rightward posing biases for head-only images. Overall, images tended to be lit from the top left corner. The two factors of posing and lighting biases appear to influence one another. Leftward-lit images had more leftward poses than rightward, while the opposite occurred for rightward-lit images. Collectively, these results demonstrate that the posing biases in advertisements are dependent on the amount of body showing in the image, and that biases in lighting direction interact with these posing biases.

Antagonism of the Ethanol-Like Discriminative Stimulus Effects of Ethanol, Pentobarbital, and Midazolam in Cynomolgus Monkeys Reveals Involvement of Specific GABAA Receptor SubtypesS⃞

PubMed Central

Rogers, Laura S. M.; Grant, Kathleen A.

2009-01-01

The γ-aminobutyric acid (GABA)A receptors mediating the discriminative stimulus effects of ethanol were studied by comparing the potency of ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)benzodiazepine-3-carboxylate (Ro15-4513) and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)-benzodiazepine-3-carboxylate (flumazenil, Ro15-1788) to antagonize ethanol, pentobarbital (PB), and midazolam substitution for ethanol. Ro15-4513 has high affinity for receptors containing α4/6 and α5 subunits and lower affinity for α1, α2, and α3 subunits. Flumazenil is nonselective for GABAA receptors containing α1, α2, α3, and α5 subunits and has low affinity for α4/6-containing receptors. Male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) were trained to discriminate ethanol (1.0 or 2.0 g/kg i.g., 30-min pretreatment) from water. Ethanol, PB, and midazolam dose-dependently substituted for ethanol (80% ethanol-appropriate responding). Ro15-4513 (0.003–0.56 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in a vast majority of monkeys tested (15/15, 16/17, and 11/12, respectively). In contrast, flumazenil (0.30–10.0 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in 9 of 16, 12 of 16, and 7 of 9 monkeys tested, respectively. In the monkeys showing antagonism with both Ro15-4513 and flumazenil, ethanol and PB substitution were antagonized more potently by Ro15-4513 than by flumazenil, whereas midazolam substitution was antagonized with similar potency. There were no sex or training dose differences, with the exception that flumazenil failed to antagonize ethanol substitution in males trained to discriminate 2.0 g/kg ethanol. GABAA receptors with high affinity for Ro15-4513 (i.e., containing α4/6 and α5 subunits) may be particularly important mediators of the multiple discriminative stimulus effects of ethanol through GABAA receptor systems. PMID:19641166

Rightward biases in free-viewing visual bisection tasks: implications for leftward responses biases on similar tasks.

PubMed

Elias, Lorin J; Robinson, Brent; Saucier, Deborah M

2005-12-01

Neurologically normal individuals exhibit strong leftward response biases during free-viewing perceptual judgments of brightness, quantity, and size. When participants view two mirror-reversed objects and they are forced to choose which object appears darker, more numerous, or larger, the stimulus with the relevant feature on the left side is chosen 60-75% of the time. This effect could be influenced by inaccurate judgments of the true centre-point of the objects being compared. In order to test this possibility, 10 participants completed three visual bisection tasks on stimuli known to elicit strong leftward response biases. Participants were monitored using a remote eye-tracking device and instructed to stare at the subjective midpoint of objects presented on a computer screen. Although it was predicted that bisection errors would deviate to the left of centre (as is the case in the line bisection literature), the opposite effect was found. Significant rightward bisection errors were evident on two of the three tasks, and the leftward biases seen during forced-choice tasks could be the result of misjudgments to the right of centre on these same tasks.

Evaluation of the Bronchorelaxant, Genotoxic, and Antigenotoxic Effects of Cassia alata L.

PubMed Central

Ouédraogo, M.; Da, F. L.; Fabré, A.; Konaté, K.; Dibala, C. I.; Carreyre, H.; Thibaudeau, S.; Coustard, J.-M.; Vandebrouck, C.; Bescond, J.; Belemtougri, R. G.

2013-01-01

Aqueous-ethanolic extract of Cassia alata (AECal) and its derived fractions obtained through liquid-liquid fractionation were evaluated for their bronchorelaxant, genotoxic, and antigenotoxic effects. Contractile activity of rats' tracheas in the presence of tested materials, as well as its modifications with different inhibitors and blockers, was isometrically recorded. The antigenotoxic potential of AECal was evaluated on cyclophosphamide- (CP-) induced genotoxicity in the rat. Animals were pretreated with the extract, then liver comet assay was performed. AECal and its chloroformic fractions (CF-AECal) relaxed the contraction induced by Ach, but both were significantly less potent in inhibiting contraction induced by KCl (30 mM; 80 mM). Propranolol, indomethacin, L-NAME, methylene blue, and glibenclamide did not modify the relaxant effect of CF-AECal. TEA altered the response of trachea to CF-AECal. CF-AECal caused a rightward shift without affecting the E max in cumulative concentration-response curves of Ach only at low concentrations. In animals pretreated with the extract, the percentage of CP-induced DNA damage decreased. Our results suggest that (1) muscarinic receptors contribute at least in part to the relaxant effects of CF-AECal; (2) CF-AECal interferes with membrane polarization; and (3) AECal is not genotoxic in vivo and contains chemopreventive phytoconstituents offering protection against CP-induced genotoxicity. PMID:23710211

The effect of operant-conditioning balance training on the down-regulation of spinal H-reflexes in a spastic patient.

PubMed

Hoseini, Najmeh; Koceja, David M; Riley, Zachary A

2011-10-24

Spasticity in chronic hemiparetic stroke patients has primarily been treated pharmacologically. However, there is increasing evidence that physical rehabilitation can help manage hyper-excitability of reflexes (hyperreflexia), which is a primary contributor to spasticity. In the present study, one chronic hemiparetic stroke patient operantly conditioned the soleus H-reflex while training on a balance board for two weeks. The results showed a minimal decrease in the Hmax-Mmax ratio for both the affected and unaffected limb, indicating that the H-reflex was not significantly altered with training. Alternatively, paired-reflex depression (PRD), a measure of history-dependent changes in reflex excitability, could be conditioned. This was evident by the rightward shift and decreased slope of reflex excitability in the affected limb. The non-affected limb decreased as well, although the non-affected limb was very sensitive to PRD initially, whereas the affected limb was not. Based on these results, it was concluded that PRD is a better index of hyperreflexia, and this measurement could be more informative of synapse function than simple H-reflexes. This study presents a novel and non-pharmacological means of managing spasticity that warrants further investigation with the potential of being translated to the clinic. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

Carey, H.V.; Tien, X.Y.; Wallace, L.J.

Muscarinic receptors involved in the secretory response evoked by electrical stimulation of submucosal neutrons were investigated in muscle-stripped flat sheets of guinea pig ileum set up in flux chambers. Neural stimulation produced a biphasic increase in short-circuit current due to active chloride secretion. Atropine and 4-diphenylacetoxy-N-methylpiperadine methiodide (4-DAMP) (10/sup -7/ M) were more potent inhibitors of the cholinergic phase of the response than was pirenzepine. Dose-dependent increases in base-line short-circuit current were evoked by carbachol and bethanechol; 4-hydroxy-2-butynyl trimethylammonium chloride (McN A343) produced a much smaller effect. Tetrodotoxin abolished the effects of McN A343 but did not alter the responsesmore » of carbachol and bethanechol. McN A343 significantly reduced the cholinergic phase of the neurally evoked response and caused a rightward shift of the carbachol dose-response curve. All muscarinic compounds inhibited (/sup 3/H)quinuclidinyl benzilate binding to membranes from muscosal scrapings, with a rank order of potency of 4-DAMP > pirenzepine > McN A343 > carbachol > bethanechol. These results suggest that acetylcholine released from submucosal neurons mediates chloride secretion by interacting with muscarinic cholinergic receptors that display a high binding affinity for 4-DAMP. Activation of neural muscarinic receptors makes a relatively small contribution to the overall secretory response.« less

Central endogenous histamine modulates sympathetic outflow through H3 receptors in the conscious rabbit

PubMed Central

Charles, Julian; Angus, James A; Wright, Christine E

2003-01-01

This study examined the role of histamine H3 receptors in vagal and sympathetic autonomic reflexes in the conscious rabbit, and in rabbit and guinea-pig isolated right atria. The baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch-like and nasopharyngeal reflexes were assessed after these treatments (i.v.; with H1 and H2 receptor block): (i) vehicle (saline; n=11); (ii) H3 receptor agonist, (R)-α-methylhistamine (R-α-MH) 100 μg kg−1+100 μg kg−1 h−1 (n=9); (iii) H3 receptor antagonist, thioperamide 1 mg kg−1+1 mg kg−1 h−1 (n=11); (iv) R-α-MH and thioperamide (n=6); and (v) H2 and H3 antagonist, burimamide 6.3 mg kg−1+6.3 mg kg−1 h−1 (n=4). R-α-MH caused a thioperamide-sensitive fall in mean arterial pressure (MAP) of 8±1 mmHg and tachycardia of 18±2 bpm (P<0.0005). Burimamide was without effect, however thioperamide elicited an increase in MAP of 4±1 mmHg (P<0.01), but no change in heart rate (HR). R-α-MH caused a 44% decrease in the average gain of the baroreflex (P=0.0001); this effect was antagonised by thioperamide. Thioperamide caused a parallel rightward shift in the barocurve with an increase in MAP of 5 mmHg (P<0.05). Burimamide had no effect on the baroreflex. The vagally mediated bradycardia elicited by the Bezold-Jarisch and nasopharyngeal reflexes was unaffected by H3 receptor ligand administration. R-α-MH (⩽10 μM) caused a thioperamide-sensitive depression of both sympathetic and vagal responses in guinea-pig atria, but had no effect in rabbit atria. As H3 receptor activation caused a significant decrease in baroreflex gain without affecting HR range, the former is unlikely to be simply due to peripheral sympatholysis (supported by the lack of effect in isolated atria). Central H3 receptors may have a tonic role in the baroreflex as thioperamide caused a rightward resetting of the barocurve. In contrast, the peripherally acting H3 antagonist burimamide was without effect. These findings suggest a role for central histamine H3 receptors in cardiovascular homeostasis in the rabbit. PMID:12839877

GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist

PubMed Central

Wilson, Richard J; Giblin, Gerard M P; Roomans, Susan; Rhodes, Sharron A; Cartwright, Kerri-Ann; Shield, Vanessa J; Brown, Jason; Wise, Alan; Chowdhury, Jannatara; Pritchard, Sara; Coote, Jim; Noel, Lloyd S; Kenakin, Terry; Burns-Kurtis, Cynthia L; Morrison, Valerie; Gray, David W; Giles, Heather

2006-01-01

N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl}benzene sulphonamide (GW627368X) is a novel, potent and selective competitive antagonist of prostanoid EP4 receptors with additional human TP receptor affinity. At recombinant human prostanoid EP4 receptors expressed in HEK293 cells, GW627368X produced parallel rightward shifts of PGE2 concentration–effect (E/[A]) curves resulting in an affinity (pKb) estimate of 7.9±0.4 and a Schild slpoe not significantly different from unity. The affinity was independent of the agonist used. In rings of phenylephrine precontracted piglet saphenous vein, GW627368X (30–300 nM) produced parallel rightward displacement of PGE2 E/[A] curves (pKb=9.2±0.2; slope=1). GW627368X appears to bind to human prostanoid TP receptors but not the TP receptors of other species. In human washed platelets, GW627368X (10 μM) produced 100% inhibition of U-46619 (EC100)-induced aggregation (approximate pA2 ∼7.0). However, in rings of rabbit and piglet saphenous vein and of guinea-pig aorta GW627368X (10 μM) did not displace U-46619 E/[A] curves indicating an affinity of <5.0 for rabbit and guinea-pig prostanoid TP receptors. In functional assays GW627368X is devoid of both agonism and antagonist affinity for prostanoid CRTH2, EP2, EP3, IP and FP receptors. At prostanoid EP1 receptors, GW627368X was an antagonist with a pA2 of 6.0, and at prostanoid IP receptors the compound increased the maximum effect of iloprost by 55%. At rabbit prostanoid EP2 receptors the pA2 of GW627368X was <5.0. In competition radioligand bioassays, GW627368X had affinity for human prostanoid EP4 and TP receptors (pKi=7.0±0.2 (n=10) and 6.8 (n=2), respectively). Affinity for all other human prostanoid receptors was <5.3. GW627368X will be a valuable tool to explore the role of the prostanoid EP4 receptor in many physiological and pathological settings. PMID:16604093

Stream Width Dynamics in a Small Headwater Catchment

NASA Astrophysics Data System (ADS)

Barefoot, E. A.; Pavelsky, T.; Allen, G. H.; Zimmer, M. A.; McGlynn, B. L.

2016-12-01

Changing streamflow conditions cause small, ephemeral and intermittent stream networks to expand and contract, while simultaneously driving widening and narrowing of streams. The resulting dynamic surface area of ephemeral streams impacts critical hydrological and biogeochemical processes, including air-water gas exchange, solute transport, and sediment transport. Despite the importance of these dynamics, to our knowledge there exists no complete study of how stream widths vary throughout an entire catchment in response to changing streamflow conditions. Here we present the first characterization of how variable hydrologic conditions impact the distribution of stream widths in a 48 ha headwater catchment in the Stony Creek Research Watershed, NC, USA. We surveyed stream widths longitudinally every 5 m on 12 occasions over a range of stream discharge from 7 L/s to 128 L/s at the catchment outlet. We hypothesize that the shape and location of the stream width distribution are driven by the action of two interrelated mechanisms, network extension and at-a-station widening, both of which increase with discharge. We observe that during very low flow conditions, network extension more significantly influences distribution location, and during high flow conditions stream widening is the dominant driver. During moderate flows, we observe an approximately 1 cm rightward shift in the distribution peak with every additional 10 L/s of increased discharge, which we attribute to a greater impact of at-a-station widening on distribution location. Aside from this small shift, the qualitative location and shape of the stream width distribution are largely invariant with changing streamflow. We suggest that the basic characteristics of stream width distributions constitute an equilibrium between the two described mechanisms across variable hydrologic conditions.

The quetiapine active metabolite N-desalkylquetiapine and the neurotensin NTS₁ receptor agonist PD149163 exhibit antidepressant-like effects on operant responding in male rats.

PubMed

Hillhouse, Todd M; Shankland, Zachary; Matazel, Katelin S; Keiser, Ashley A; Prus, Adam J

2014-12-01

Major depressive disorder is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that is apparent after 1 week of treatment, and it is possible that the active metabolite N-desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS1 receptor agonist PD149163 suggest antidepressant efficacy, but the effects of a NTS₁ receptor agonist in an antidepressant animal model have yet to be reported. The present study examined the antidepressant-like effects of N-desalkylquetiapine, PD14916, quetiapine, the tricyclic antidepressant drug imipramine, the atypical antipsychotic drug risperidone, and the typical antipsychotic drug raclopride on responding in male Sprague-Dawley rats trained on a differential-reinforcement-of-low-rate 72-s operant schedule, a procedure used for screening antidepressant drugs. Quetiapine, PD149163, risperidone, and imipramine exhibited antidepressant-like effects by increasing the number of reinforcers earned, decreasing the number of responses emitted, and shifting the interresponse time (IRT) distributions to the right. N-Desalkylquetiapine produced a partial antidepressant-like effect by decreasing the number of responses emitted and producing a rightward shift in the IRT distributions, but it did not significantly alter the number of reinforcers earned. Raclopride decreased reinforcers and responses. These data suggest that N-desalkylquetiapine likely contributes to quetiapine's antidepressant efficacy and identify NTS₁ receptor activation as a potential novel pharmacologic strategy for antidepressant drugs. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Postimplant left ventricular assist device fit analysis using three-dimensional reconstruction.

PubMed

Truong, Thang V; Stanfield, J Ryan; Chaffin, John S; Elkins, C Craig; Kanaly, Paul J; Horstmanshof, Douglas A; Long, James W; Snyder, Trevor A

2013-01-01

Left ventricular assist devices (LVADs) are blood pumps that augment the function of the failing heart to improve perfusion, resulting in improved survival. For LVADs to effectively unload the left ventricle, the inflow cannula (IC) should be unobstructed and ideally aligned with the heart's mitral valve (MV). We examined IC orientation deviation from a hypothesized conventional angle (45° right-posterior) and the approximate angle for direct IC-MV alignment in many patients. Three-dimensional anatomic models were created from computed tomography scans for 24 LVAD-implanted patients, and angles were measured between the IC and the apical z-axis in both the coronal and the sagittal planes. Common surgical IC angulation was found to be 22 ± 15° rightward and 21 ± 12° posterior from the apical z-axis; 38% (n = 9) of patients fell in this range. Direct IC-MV angulation was found to be 34 ± 8° rightward and 15 ± 7° posterior; only 8% (n = 2) of patients fell in this range. Rightward deviation toward ventricular septal wall and anterior deviation toward LV anterior freewall are associated with mortalities more so than leftward and posterior deviation. In conclusion, anatomic reconstruction may be a useful preoperative tool to obtain general population and patient-specific alignment for optimal LVAD implantation.

Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation.

PubMed

Mekkaoui, Choukri; Huang, Shuning; Chen, Howard H; Dai, Guangping; Reese, Timothy G; Kostis, William J; Thiagalingam, Aravinda; Maurovich-Horvat, Pal; Ruskin, Jeremy N; Hoffmann, Udo; Jackowski, Marcel P; Sosnovik, David E

2012-10-12

The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p < 0.05). This was confirmed histologically by the reduction of HA in the subepicardium from -52.03° ± 2.94° in normal hearts to -37.48° ± 4.05° in the remote zone of the remodeled hearts (p < 0.05). A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids.

PubMed

Cunningham, Colin S; McMahon, Lance R

2013-07-01

Receptor mechanisms underlying the behavioral effects of clinically used nicotinic acetylcholine receptor agonists have not been fully established. Drug discrimination was used to compare receptor mechanisms underlying the effects of smoking cessation aids. Separate groups of male C57BL/6J mice discriminated 0.56, 1, or 1.78 mg/kg of nicotine base. Nicotine, varenicline, and cytisine were administered alone, in combination with each other, and in combination with mecamylamine and dihydro-β-erythroidine (DHβE). Midazolam and morphine were tested to examine sensitivity to non-nicotinics. The ED50 value of nicotine to produce discriminative stimulus effects systematically increased as training dose increased. Varenicline and cytisine did not fully substitute for nicotine and, as compared with nicotine, their ED50 values varied less systematically as a function of nicotine training dose. Morphine did not substitute for nicotine, whereas midazolam substituted for the low and not the higher training doses of nicotine. As training dose increased, the dose of mecamylamine needed to produce a significant rightward shift in the nicotine dose-effect function also increased. DHβE antagonized nicotine in animals discriminating the smallest dose of nicotine. Varenicline did not antagonize the effects of nicotine, whereas cytisine produced a modest though significant antagonism of nicotine. These results suggest that differences in pharmacologic mechanism between nicotine, varenicline, and cytisine include not only differences in efficacy at a common subtype of nicotinic acetylcholine receptor, but also differential affinity and/or efficacy at multiple receptor subtypes.

When advertising turns "cheeky"!

PubMed

Burkitt, Jennifer A; Saucier, Deborah M; Thomas, Nicole A; Ehresman, Crystal

2006-05-01

Portraits typically exhibit leftward posing biases, with people showing more of their left cheek than their right. The current study investigated posing biases in print advertising to determine whether the product advertised affects the posing bias. As the posing bias may be decreasing over time, we also investigated changes in posing biases over a span of more than 100 years. The current investigation coded 2664 advertisements from two time periods; advertisements were coded for target group of advertisement (men, women, both) and posing bias (rightward, leftward, or central). Unlike other studies that typically observe a leftward posing bias, print advertisements exhibit a rightward posing bias, regardless of time-frame. Thus, print advertisements differ greatly from portraits, which may relate to the purpose of advertisements and the role of attractiveness in advertising.

Spatial Dynamics of Multilayer Cellular Neural Networks

NASA Astrophysics Data System (ADS)

Wu, Shi-Liang; Hsu, Cheng-Hsiung

2018-02-01

The purpose of this work is to study the spatial dynamics of one-dimensional multilayer cellular neural networks. We first establish the existence of rightward and leftward spreading speeds of the model. Then we show that the spreading speeds coincide with the minimum wave speeds of the traveling wave fronts in the right and left directions. Moreover, we obtain the asymptotic behavior of the traveling wave fronts when the wave speeds are positive and greater than the spreading speeds. According to the asymptotic behavior and using various kinds of comparison theorems, some front-like entire solutions are constructed by combining the rightward and leftward traveling wave fronts with different speeds and a spatially homogeneous solution of the model. Finally, various qualitative features of such entire solutions are investigated.

Influence of gravity on cardiac performance.

PubMed

Pantalos, G M; Sharp, M K; Woodruff, S J; O'Leary, D S; Lorange, R; Everett, S D; Bennett, T E; Shurfranz, T

1998-01-01

Results obtained by the investigators in ground-based experiments and in two parabolic flight series of tests aboard the NASA KC-135 aircraft with a hydraulic simulator of the human systemic circulation have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume of 20%-50%. A corresponding drop in stroke volume (SV) and cardiac output (CO) was observed over a range of atrial pressures (AP), representing a rightward shift of the classic CO versus AP cardiac function curve. These results are in agreement with echocardiographic experiments performed on space shuttle flights, where an average decrease in SV of 15% was measured following a three-day period of adaptation to weightlessness. The similarity of behavior of the hydraulic model to the human system suggests that the simple physical effects of the lack of hydrostatic pressure may be an important mechanism for the observed changes in cardiac performance in astronauts during the weightlessness of space flight.

Kinetic Behavior and Microstructure of Pearlite Isothermal Transformation Under High Undercooling

NASA Astrophysics Data System (ADS)

Liang, Yu; Xu, Pingwei; Xiang, Song; Liang, Yilong; Xiong, Hu; Li, Jing

2018-06-01

The kinetic behavior of highly undercooled austenite and its effects on the microstructural evolution and mechanical properties of high-carbon steel are studied. The undercooling degree is increased through a temporary undercooling treatment at the bainite transformation temperature of 380 °C to 450 °C before the pearlite isothermal transformation at 500 °C to 620 °C. The transformation kinetics reveals an increased nose temperature and a rightward shift of the transformation curve under high undercooling conditions. In addition, the undercooling treatment leads to an increased driving force during pearlite transformation, which is responsible for the refined hierarchical structures of pearlite. As a result, a 20 to 40 pct size reduction is achieved for pearlite colonies and lamellae. Such refinement is in turn attributed to an 26 pct increase in reduction in area. This work provides both a new understanding of high-performance fully pearlitic steels for practical applications and new perspectives for potential technological applications in drawing processes for hypoeutectoid steels.

Behavioural laterality as a predictor of health in captive Caribbean flamingos (Phoenicopterus ruber): an exploratory analysis.

PubMed

Anderson, Matthew J; Ialeggio, Donna M

2014-01-01

The present study sought to explore the possibility that lateral behaviour in captive Caribbean flamingos (Phoenicopterus ruber) housed at the Philadelphia Zoo (Philadelphia, PA) could be used to predict a variety of physiological measures of health obtained via complete blood counts (CBC) and plasma biochemistry analyses that were performed as part of the flock's annual physical examination. Consistent with previous research, evidence of rightward lateral neck-resting preferences were obtained, no evidence was found for the existence of leg stance preferences, and neck-resting and leg stance preferences were shown to be unrelated. Both lateral neck-resting preferences and lateral support leg preference were shown to be related to a variety of measures from the CBC and plasma biochemistry analyses. While several general trends emerged in regards to the CBC variables, the relationships between the lateral behaviours and those variables generated via plasma biochemistry analyses proved to be fewer and somewhat less consistent. Birds with rightward neck-resting preferences and birds with leftward support leg preferences generally appeared to be healthier and less stressed according to the CBC measures; however, the validity of lateral leg stance preference as a predictor of health and wellbeing is questionable given the lack of statistically significant leg stance preferences.

Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

PubMed

Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

2017-10-01

Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

Competitive antagonists discriminate between NK2 tachykinin receptor subtypes.

PubMed Central

Maggi, C. A.; Patacchini, R.; Giuliani, S.; Rovero, P.; Dion, S.; Regoli, D.; Giachetti, A.; Meli, A.

1990-01-01

1. We have compared the ability of various tachykinins and selective tachykinin receptor agonists to induce contraction of the endothelium-denuded rabbit pulmonary artery (RPA) and hamster trachea (HT) and have estimated the affinity of some newly developed NK2 selective antagonists in the same tissues. 2. In confirmation of previous findings, experiments with the agonists indicated that NK2 receptors are the main if not the sole mediators of the response to tachykinins in both RPA and HT. No evidence for significant degradation of neurokinin A (NKA) was found in either tissue when experiments were repeated in the presence of a mixture of peptidase inhibitors (thiorphan, captopril and bestatin, 1 microM each). 3. The peptide antagonists tested were: Peptide I = [Tyr5, D-Trp6,8,9, Arg10]-NKA(4-10); Peptide II = [Tyr5, D-Trp6,8,9, Arg10]-NKA(3-10); Peptide III = Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2. The three peptides produced a concentration-dependent rightward shift of the concentration-response curve to NKA in both RPA and HT with no significant depression of the maximal response attainable. The slopes of the Schild plots were not significantly different from unity, indicating a competitive antagonism. Peptides I and II were about 100 times more potent in the RPA than in the HT, while Peptide III was about 100 times more potent in the HT than RPA. 4. The pA2 values obtained in these two tissues with the three antagonists were not significantly different when tested in the absence or presence of peptidase inhibitors, or when a selective NK2 receptor agonist, [beta Ala8]-NKA(4-10) was used instead of NKA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2167737

Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay

PubMed Central

Lai, Meng‐Chuan; Auer, Tibor; Lombardo, Michael V.; Ecker, Christine; Chakrabarti, Bhismadev; Wheelwright, Sally J.; Bullmore, Edward T.; Murphy, Declan G.M.; Baron‐Cohen, Simon; Suckling, John

2015-01-01

Abstract In humans, both language and fine motor skills are associated with left‐hemisphere specialization, whereas visuospatial skills are associated with right‐hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right‐handed adults with ASC and 69 age‐ and IQ‐matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel‐based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC. Hum Brain Mapp 37:230–253, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26493275

Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function

PubMed Central

Fomovsky, Gregory M.; Clark, Samantha A.; Parker, Katherine M.; Ailawadi, Gorav; Holmes, Jeffrey W.

2012-01-01

Background We hypothesize that a therapy that improves LV pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of left ventricular (LV) function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, while isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. Methods and Results We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at Baseline, 45 minutes after coronary ligation (Ischemia), and 30 minutes later, following surgical reinforcement in the longitudinal direction (Anisotropic). Ischemia shifted the end-systolic pressure-volume relationship (ESPVR) and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure (EDP) by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. Conclusions We conclude that anisotropic reinforcement is a promising new approach to improving LV function following a large myocardial infarction. PMID:22665716

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia.

PubMed

Kingma, J G; Linderoth, B; Ardell, J L; Armour, J A; DeJongste, M J; Foreman, R D

2001-08-13

Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator.

PubMed

Orito, K; Kishi, M; Imaizumi, T; Nakazawa, T; Hashimoto, A; Mori, T; Kambe, T

2001-10-01

1. Antagonistic properties of OPC-28326 ([4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl)] piperidine hydrochloride monohydrate), a selective peripheral vasodilator, were investigated by analysing the data from functional studies in various tissues from the rat and binding studies of the drug to alpha(2)-adrenoceptor subtypes. 2. Using a human recombinant receptor and rat kidney cortex, we found that OPC-28326 displays affinities to alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors with K(i) values of 2040, 285, and 55 nM, respectively. The K(i) values of yohimbine for alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenoceptors were 3.0, 2.0 and 11.0 nM, respectively. 3. B-HT 920, an alpha(2)-adrenoceptor agonist, produced a pressor response via peripheral postsynaptic alpha(2)-adrenoceptor stimulation (thought to be an alpha(2B)-subtype) in a reserpine-pretreated pithed rat preparation. OPC-28326 (3 - 30 mg kg(-1), i.v.) and yohimbine (0.3 - 3 mg kg(-1), i.v.) caused dose-dependent rightward shift in the pressor dose-response curve induced by B-HT 920. The apparent pA(2) values were 1.55 (0.87 - 2.75, 95% confidence interval) and 0.11 (0.06 - 0.21) mg kg(-1), respectively. The potency of OPC-28326 was about 14 times less than that of yohimbine. 4. Clonidine inhibited the tension developed by electrical stimulation, of the rat vas deferens, by its peripheral presynaptic alpha(2A/D)-adrenoceptor action. OPC-28326 (1 - 100 microM) and yohimbine (10 - 1000 nM) caused a rightward shift in the concentration-response curve of clonidine. The pA(2) values were 5.73 (5.54 - 5.91) and 7.92 (7.84 - 8.01), respectively, providing evidence for a potency of OPC-28326 of about 155 times less than that of yohimbine. 5. Mydriasis was induced by brimonidine via stimulation of central alpha(2A/D)-adrenoceptors in anaesthetized rats. Intravenous OPC-28326 had no effect on this action, even at a very high dose of 10 mg kg(-1) i.v., while yohimbine (0.1 - 0.3 mg kg(-1) i.v.) inhibited mydriasis in a dose-dependent manner, indicating that OPC-28326 was at least 100 times less potent than yohimbine in regard to the anti-mydriatic effect. 6. These data suggest that OPC-28326 preferentially exerts peripheral and postsynaptic antagonistic actions on the alpha(2B)- and alpha(2C)-adrenoceptor subtypes.

Prism adaptation in Parkinson disease: comparing reaching to walking and freezers to non-freezers.

PubMed

Nemanich, Samuel T; Earhart, Gammon M

2015-08-01

Visuomotor adaptation to gaze-shifting prism glasses requires recalibration of the relationship between sensory input and motor output. Healthy individuals flexibly adapt movement patterns to many external perturbations; however, individuals with cerebellar damage do not adapt movements to the same extent. People with Parkinson disease (PD) adapt normally, but exhibit reduced after-effects, which are negative movement errors following the removal of the prism glasses and are indicative of true spatial realignment. Walking is particularly affected in PD, and many individuals experience freezing of gait (FOG), an episodic interruption in walking, that is thought to have a distinct pathophysiology. Here, we examined how individuals with PD with (PD + FOG) and without (PD - FOG) FOG, along with healthy older adults, adapted both reaching and walking patterns to prism glasses. Participants completed a visually guided reaching and walking task with and without rightward-shifting prism glasses. All groups adapted at similar rates during reaching and during walking. However, overall walking adaptation rates were slower compared to reaching rates. The PD - FOG group showed smaller after-effects, particularly during walking, compared to PD + FOG, independent of adaptation magnitude. While FOG did not appear to affect characteristics of prism adaptation, these results support the idea that the distinct neural processes governing visuomotor adaptation and storage are differentially affected by basal ganglia dysfunction in PD.

Endomorphin-2 analogs with C-terminal esterification produce potent systemic antinociception with reduced tolerance and gastrointestinal side effects.

PubMed

Wang, Chang-Lin; Qiu, Ting-Ting; Yang, Dai-Jun; Yuan, Bi-Yu; Han, Feng-Tong; Li, Li; Gu, Ning

2017-04-01

C-terminal esterification of opioid peptides may change their opioid activities due to the modified physicochemical properties. In the present study, the pharmacological activities of C-terminal esterified endomorphin-2 (EM-2) analogs 1-3 were characterized by in vitro metabolic stability and octanol/buffer distribution assays. Also, the antinociceptive profiles in the radiant heat paw withdrawal test and related side effects of these analogs were determined. Our results showed that all three analogs significantly increased the metabolic stability and lipophilicity. Moreover, analogs 1-3 displayed potent antinociceptive activities after intracerebroventricular (i.c.v.) administration. Analogs 1 and 3 exhibited about 2-fold higher antinociception than EM-2, and differential opioid mechanisms were involved. In addition, EM-2 at 50 μmol/kg failed to produce any significant antinociceptive activity after subcutaneous (s.c.) administration, whereas equimolar dose of analogs 1-3 produced significant analgesic effects. Analog 3 showed the highest antinociceptive activity after systemic administration, which was consistent with its in vitro stability and lipophilicity. We further evaluated the antinociceptive tolerance of analogs 1-3. In acute tolerance test, analogs 1-3 shifted the dose-response curves rightward by only 1.4-3.2 fold as determined by tolerance ratio, whereas EM-2 by 5.6-fold, demonstrating reduced antinociceptive tolerance. Also, analogs 1 and 2 decreased chronic antinociceptive tolerance by central and peripheral administration of drugs. In particular, analogs 3 displayed insignificant chronic antinociceptive tolerance. Furthermore, analogs 1-3 were less prone to induce gastrointestinal side effects at analgesic doses. The present investigation gave the evidence that C-terminal esterified modifications of EM-2 will facilitate the development of novel opioid analgesics with reduced side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vitro contractile effects of neurokinin receptor blockade in the human ureter.

PubMed

Nakada, S Y; Jerde, T J; Bjorling, D E; Saban, R

2001-10-01

We identified the predominance of neurokinin-2 receptors and evaluated the inhibition of spontaneous contraction via the blockade of neurokinin-2 receptors in human ureteral segments. Excess ureteral segments from human subjects undergoing donor nephrectomy or reconstructive procedures were suspended in tissue baths containing Krebs buffer. After spontaneous contractions were recorded, tissues were incubated with 1 microM. solutions of phosphoramidon and captopril (to inhibit peptide degradation) and either the neurokinin-1 receptor antagonist CP 99,994, the neurokinin-2 receptor antagonist SR 48,968, the neurokinin-3 receptor antagonist SR 142,801 or dimethyl sulfoxide (control) for 1 hour. Contraction magnitude and frequency were again recorded and compared with spontaneous levels. Concentration-response curves to the tachykinins substance P, and neurokinins A and B were determined in the presence and absence of antagonists. Neurokinin A increased contractility at lower concentrations than substance P or neurokinin B (p <0.013). Neurokinin-2 receptor blockade produced a 100-fold rightward shift of the concentration-response curves (p <0.013), while neurokinins 1 and 3 receptor blockade had no effect. SR 48,968 significantly reduced contractility during the 1-hour incubation period, causing a 97% reduction in spontaneous rates compared with a 29% reduction in control tissues. CP 99,994 and SR 142,801 had no significant effect. Neurokinin-2 is the predominant receptor subtype responsible for tachykinin induced contraction of human ureteral smooth muscle. In vitro treatment with the neurokinin-2 antagonist SR 48,968 reduces the spontaneous contraction rate by 97% in vitro. Neurokinin-2 receptor antagonists may have clinical applications for ureteral disease.

Mechanical origins of rightward torsion in early chick brain development

NASA Astrophysics Data System (ADS)

Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

2015-03-01

During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

Translation and articulation in biological motion perception.

PubMed

Masselink, Jana; Lappe, Markus

2015-08-01

Recent models of biological motion processing focus on the articulational aspect of human walking investigated by point-light figures walking in place. However, in real human walking, the change in the position of the limbs relative to each other (referred to as articulation) results in a change of body location in space over time (referred to as translation). In order to examine the role of this translational component on the perception of biological motion we designed three psychophysical experiments of facing (leftward/rightward) and articulation discrimination (forward/backward and leftward/rightward) of a point-light walker viewed from the side, varying translation direction (relative to articulation direction), the amount of local image motion, and trial duration. In a further set of a forward/backward and a leftward/rightward articulation task, we additionally tested the influence of translational speed, including catch trials without articulation. We found a perceptual bias in translation direction in all three discrimination tasks. In the case of facing discrimination the bias was limited to short stimulus presentation. Our results suggest an interaction of articulation analysis with the processing of translational motion leading to best articulation discrimination when translational direction and speed match articulation. Moreover, we conclude that the global motion of the center-of-mass of the dot pattern is more relevant to processing of translation than the local motion of the dots. Our findings highlight that translation is a relevant cue that should be integrated in models of human motion detection.

Intrinsic domain wall flexing from current-induced spin torque

NASA Astrophysics Data System (ADS)

Golovatski, Elizabeth; Flatté, Michael

2012-02-01

Spin torque generated by coherent carrier transport in domain walls [1] is a major component in the development of spintronic devices [2]. We model spin torque in N'eel walls [3] using a piecewise linear transfer-matrix method [4] to calculate spin torque on interior wall segments. For a π wall with a total positive torque (current left-to-right), we find the largest positive and negative spin torques left of the central region, 4-5 orders of magnitude larger than the center. The wall's rightward push comes from the back of the wall; all other significant regions pull to the left. Adding a second wall (both walls with positive total torque) changes the first wall little, but produces spin torques in the second wall with large canceling torques on the left, and the push rightward from a smaller torque on the right. The gradient of torque across the wall generates an intrinsic domain wall flexing (distinct from extrinsic wall flexing from pinning centers [5]). Work supported by an ARO MURI.[4pt] [1] M. Yamanouchi et al., Nature 428, 539 (2004).[0pt] [2] S. Parkin et al., Science 320, 190 (2008)[0pt] [3] G. Vignale and M. Flatt'e, Phys. Rev. Lett. 89, 098302 (2002)[0pt] [4] E. Golovatski and M. Flatt'e, Phys. Rev. B, 84, 115210 (2011)[0pt] [5] A. Balk et al., Phys. Rev. Lett. 107, 077205 (2011).

Developmental Changes in Topological Asymmetry Between Hemispheric Brain White Matter Networks from Adolescence to Young Adulthood.

PubMed

Zhong, Suyu; He, Yong; Shu, Hua; Gong, Gaolang

2017-04-01

Human brain asymmetries have been well described. Intriguingly, a number of asymmetries in brain phenotypes have been shown to change throughout the lifespan. Recent studies have revealed topological asymmetries between hemispheric white matter networks in the human brain. However, it remains unknown whether and how these topological asymmetries evolve from adolescence to young adulthood, a critical period that constitutes the second peak of human brain and cognitive development. To address this question, the present study included a large cohort of healthy adolescents and young adults. Diffusion and structural magnetic resonance imaging were acquired to construct hemispheric white matter networks, and graph-theory was applied to quantify topological parameters of the hemispheric networks. In both adolescents and young adults, rightward asymmetry in both global and local network efficiencies was consistently observed between the 2 hemispheres, but the degree of the asymmetry was significantly decreased in young adults. At the nodal level, the young adults exhibited less rightward asymmetry of nodal efficiency mainly around the parasylvian area, posterior tempo-parietal cortex, and fusiform gyrus. These developmental patterns of network asymmetry provide novel insight into the human brain structural development from adolescence to young adulthood and also likely relate to the maturation of language and social cognition that takes place during this period. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Exploring the Relationship Between Cerebellar Asymmetry and Handedness in Chimpanzees (Pan troglodytes) and Capuchins (Cebus apella)

PubMed Central

Phillips, Kimberley A.; Hopkins, William D.

2007-01-01

A comparative study of chimpanzee (Pan troglodytes) and capuchin monkey (Cebus apella) cerebellar asymmetry and its relationship to handedness was conducted. Magnetic resonance images of the brain and behavioral data on a coordinated bimanual task were obtained from 16 chimpanzees and 11 capuchins. Chimpanzees displayed a greater rightward bias of the posterior cerebellum and capuchins displayed a greater leftward bias of the anterior cerebellum. Cerebellar asymmetries were significantly associated with handedness in capuchins but not chimpanzees, and this effect was most pronounced in right-handed capuchins. PMID:17382360

[Colorectal cancer the importance of primary tumor location].

PubMed

Ryska, M; Bauer, J

2017-01-01

Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.

The role of the right superior temporal gyrus in stimulus-centered spatial processing.

PubMed

Shah-Basak, Priyanka P; Chen, Peii; Caulfield, Kevin; Medina, Jared; Hamilton, Roy H

2018-05-01

Although emerging neuropsychological evidence supports the involvement of temporal areas, and in particular the right superior temporal gyrus (STG), in allocentric neglect deficits, the role of STG in healthy spatial processing remains elusive. While several functional brain imaging studies have demonstrated involvement of the STG in tasks involving explicit stimulus-centered judgments, prior rTMS studies targeting the right STG did not find the expected neglect-like rightward bias in size judgments using the conventional landmark task. The objective of the current study was to investigate whether disruption of the right STG using inhibitory repetitive transcranial magnetic stimulation (rTMS) could impact stimulus-centered, allocentric spatial processing in healthy individuals. A lateralized version of the landmark task was developed to accentuate the dissociation between viewer-centered and stimulus-centered reference frames. We predicted that inhibiting activity in the right STG would decrease accuracy because of induced rightward bias centered on the line stimulus irrespective of its viewer-centered or egocentric locations. Eleven healthy, right-handed adults underwent the lateralized landmark task. After viewing each stimulus, participants had to judge whether the line was bisected, or whether the left (left-long trials) or the right segment (right-long trials) of the line was longer. Participants repeated the task before (pre-rTMS) and after (post-rTMS) receiving 20 min of 1 Hz rTMS over the right STG, the right supramarginal gyrus (SMG), and the vertex (a control site) during three separate visits. Linear mixed models for binomial data were generated with either accuracy or judgment errors as dependent variables, to compare 1) performance across trial types (bisection, non-bisection), and 2) pre- vs. post-rTMS performance between the vertex and the STG and the vertex and the SMG. Line eccentricity (z = 4.31, p < 0.0001) and line bisection (z = 5.49, p < 0.0001) were significant predictors of accuracy. In the models comparing the effects of rTMS, a significant two-way interaction with STG (z = -3.09, p = 0.002) revealed a decrease in accuracy of 9.5% and an increase in errors of the right-long type by 10.7% on bisection trials, in both left and right viewer-centered locations. No significant changes in leftward errors were found. These findings suggested an induced stimulus-centered rightward bias in our participants after STG stimulation. Notably, accuracy or errors were not influenced by SMG stimulation compared to vertex. In line with our predictions, the findings provide compelling evidence for right STG's involvement in healthy stimulus-centered spatial processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Control over Conflict during Movement Preparation: Role of Posterior Parietal Cortex

PubMed Central

Coulthard, Elizabeth J.; Nachev, Parashkev; Husain, Masud

2008-01-01

Summary Flexible behavior in humans often requires that rapid choices be made between conflicting action plans. Although much attention has focused on prefrontal regions, little is understood about the contribution of parietal cortex under situations of response conflict. Here we show that right parietal damage associated with spatial neglect leads to paradoxical facilitation (speeding) of rightward movements in the presence of conflicting leftward response plans. These findings indicate a critical role for parietal regions in action planning when there is response competition. In contrast, patients with prefrontal damage have an augmented cost of conflict for both leftward and rightward movements. The results suggest involvement of two independent systems in situations of response conflict, with right parietal cortex being a crucial site for automatic activation of competing motor plans and prefrontal regions acting independently to inhibit action plans irrelevant to current task goals. PMID:18400170

Effect of the dB-c-AMP and forskolin on /sup 45/Ca influx, net Ca uptake and tension on rabbit aortic smooth muscle

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

Not Available

1986-03-01

The effect of dibutiryl-adenosine-3',5'-cyclic-monophosphate (dB-c-AMP) and forskolin on aortic tension and /sup 45/Ca influx were measured. dB-c-AMP reduced both the rate of force development and the maximal tension achieved in solutions containing various K/sup +/ concentrations. Stimulated /sup 45/Ca influx was also reduced however to a lesser extent than was the tension. Forskolin showed more marked effects of a similar nature. Thus, both these agents which increase intracellular c-AMP caused a rightward shift in the curve expressing force(ordinate) as a function of Ca influx (abscissa). Consequently, they found that dB-c-AMP stimulated more net Ca to be taken up by themore » sarcoplasmic reticulum(SR) at the same influx rate. The conclusion that c-AMP produced these effects by stimulating Ca uptake into the superficial SR was supported by the finding that dB-c-AMP increased the amount of Ca taken up into a caffeine releasable fraction.« less

Adaptation of Timing Behavior to a Regular Change in Criterion

PubMed Central

Sanabria, Federico; Oldenburg, Liliana

2013-01-01

This study examined how operant behavior adapted to an abrupt but regular change in the timing of reinforcement. Pigeons were trained on a fixed interval (FI) 15-s schedule of reinforcement during half of each experimental session, and on an FI 45-s (Experiment 1), FI 60-s (Experiment 2), or extinction schedule (Experiment 3) during the other half. FI performance was well characterized by a mixture of two gamma-shaped distributions of responses. When a longer FI schedule was in effect in the first half of the session (Experiment 1), a constant interference by the shorter FI was observed. When a shorter FI schedule was in effect in the first half of the session (Experiments 1, 2, and 3), the transition between schedules involved a decline in responding and a progressive rightward shift in the mode of the response distribution initially centered around the short FI. These findings are discussed in terms of the constraints they impose to quantitative models of timing, and in relation to the implications for information-based models of associative learning. PMID:23962672

Mechanisms mediating substance P-induced contraction in the rat iris in vitro.

PubMed

Grumann-Júnior, A; Dias, M A; Alves, R V; Boteon, J E; Calixto, J B

2000-06-01

To determine some of the mechanisms by which substance P (SP) induces contraction in the isolated rat iris. Rings of rat iris were mounted in a 5-ml organ chamber containing Krebs solution at 37 degrees C under basal tension of 75 mg, and isometric tension was recorded. Substance P produced graded contraction in the rat iris, being approximately 40-fold more potent than carbachol. Peptidase inhibitors (captopril, phosphoramidon, thiorphan) did not affect the SP response. The SP contraction was dependent on external Ca2+ by a mechanism resistant to both nifedipine and omega-conotoxin GVIA. Atropine and tetrodotoxin significantly shifted the SP response to the right (three- and fivefold, respectively). Neither phorbol nor genistein altered the SP-induced contraction, whereas staurosporine caused a weak inhibition. Indomethacin, pyrilamine, guanethidine, 8-37 calcitonin gene-related peptide (CGRP) fragment, and NG-nitro-L-arginine methyl ester had no effect on SP response. All the natural tachykinin agonists caused concentration-dependent contraction in rat iris with similar maximal responses. The NK3 selective agonist senktide caused graded contraction, being approximately 150-fold more active than the NK2 selective agonist [beta-ala] NKA. The NK1 selective agonist SP methyl ester induced a small contraction. The NK3 and NK2 antagonists SR 142801 and SR 48968 shifted the SP response to the right. Schilds plots gave pA2 (negative logarithm of the molar concentration of antagonist causing a twofold rightward displacement of the concentration response curves) values of 9.37 and 7.97 and slopes of 0.70 and 1.02, respectively. Substance P produces a potent contraction in the isolated rat iris that seems to depend on the neural release of acetylcholine by tetrodotoxin-sensitive mechanisms. Its response relies largely on external Ca2+, through mechanisms independent of activation of L- or N-type Ca2+ channels, and is probably mediated via activation of NK3 and NK2 receptors.

6-[N,S-dimethyl-N'-cyanothioureidomethyl]-6,11-dihydro-5H- dibenz[b,e]azepine hydrochloride (Fran 12): a histamine and 5-hydroxytryptamine antagonist with pressor properties.

PubMed

Law, S C; Guyett, F J; King, R G; Boura, A L; Jackson, W R; Hodgson, W C

1992-01-01

We have synthesized and examined some of the pharmacological properties of 6-[N,S-dimethyl-N'-cyanoisothioureidomethyl]-6,11-dihydro-5H- dibenz(b,e)azepine hydrochloride (Fran 12), a derivative of 6-methylaminomethyl-6,11-dihydro-5H- dibenz[b,e,]azepine. In the guinea-pig isolated ileum, Fran 12 (10(-7)-10(-5) M) caused parallel rightward shifts of the concentration-response curves to histamine. A Schild plot gave a pA2 of 7.48, with a slope not significantly different from -1.0. In the rat stomach fundus strip and in endothelium-denuded aortic rings, Fran 12 inhibited contractile responses to 5-hydroxytryptamine in a non-competitive manner. In both chloralose-anaesthetized and pithed rats, it inhibited pressor responses to 5-hydroxytryptamine. It had no effect on depressor responses to 5-hydroxytryptamine in anaesthetized rats. In pithed rats, Fran 12 (0.25-2 mg/kg, i.v.) produced dose-dependent increases in blood pressure. These were not inhibited by i.v. phentolamine, prazosin, yohimbine, propranolol, methysergide, pentolinium or atropine but were inhibited by verapamil. These results indicate that Fran 12 is a histamine and 5-hydroxytryptamine antagonist which also exerts pressor effects via a peripheral action. The pressor action does not appear to be mediated via effects on alpha 1- or alpha 2-adrenoceptors, muscarinic or nicotinic cholinoceptors or 5-hydroxytryptamine receptors, although calcium channel activation may play a role.

Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

PubMed

Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

2014-01-01

Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

Exercise attenuates the anti-lipolytic effect of adenosine in adipocytes isolated from miniature swine.

PubMed

Carey, G B; Sidmore, K A

1994-03-01

Four pairs of female and six pairs of male litter-mate Yucatan miniature swine (Sus scrofa) were used in this study which examined the possibility that endurance exercise training reduces the sensitivity of adipocytes to the anti-lipolytic effects of adenosine. One member of each pair was exercise-trained on a treadmill for three months while its litter-mate remained sedentary, after which time over-the-shoulder fat and left brachialis muscle were biopsied. Despite a predominance of type IIB fibres, biopsied muscle of exercised swine had 38% more citrate synthase activity than controls (P < 0.05). The average cell diameters of adipocytes isolated from exercisers were 14% smaller (P < 0.05) than those from controls. Rates of adrenaline-stimulated lipolysis expressed as nmol glycerol released/90 min incubation period per 10,000 cells failed to differ between the two groups; however, when expressed per cm2 surface area, a significant 37% increase was observed. Incubation with 1 microM adrenaline and increasing doses of phenylisopropyladenosine (PIA) caused a rightward shift in the dose-response curve of adipocytes in five of the ten exercisers compared to litter-mate controls. The concentration of PIA causing one-half inhibition of lipolysis was 64% greater in adipocytes from exercisers than controls (4.03 nM vs. 2.49 nM, n = 10, P < 0.05). These data support the hypothesis that endurance exercise-training induces a reduction in adipocyte sensitivity to adenosine, thereby facilitating fatty acid mobilization.

Prenatal choline supplementation increases sensitivity to contextual processing of temporal information

PubMed Central

Buhusi, Catalin V.; Lamoureux, Jeffrey A.; Meck, Warren H.

2008-01-01

The effects of prenatal choline availability on contextual processing in a 30-s peak-interval (PI) procedure with gaps (1, 5, 10, and 15 s) were assessed in adult male rats. Neither supplementation nor deprivation of prenatal choline affected baseline timing performance in the PI procedure. However, prenatal choline availability significantly altered the contextual processing of gaps inserted into the to-be-timed signal (light on). Choline-supplemented rats displayed a high degree of context sensitivity as indicated by clock resetting when presented with a gap in the signal (light off). In contrast, choline-deficient rats showed no such effect and stopped their clocks during the gap. Control rats exhibited an intermediate level of contextual processing in between stop and full reset. When switched to a reversed gap condition in which rats timed the absence of the light and the presence of the light served as a gap, all groups reset their clocks following a gap. Furthermore, when filling the intertrial interval (ITI) with a distinctive stimulus (e.g., sound), both choline-supplemented and control rats rightward shifted their PI functions less on trials with gaps than choline-deficient rats, indicating greater contextual sensitivity and reduced clock resetting under these conditions. Overall, these data support the view that prenatal choline availability affects the sensitivity to the context in which gaps are inserted in the to-be-timed signal, thereby influencing whether rats run, stop, or reset their clocks. PMID:18778696

Impacts of typhoon megi (2010) on the South China Sea

NASA Astrophysics Data System (ADS)

Ko, Dong Shan; Chao, Shenn-Yu; Wu, Chun-Chieh; Lin, I.-I.

2014-07-01

In October 2010, typhoon Megi induced a profound cold wake of size 800 km by 500 km with sea surface temperature cooling of 8°C in the South China Sea (SCS). More interestingly, the cold wake shifted from the often rightward bias to both sides of the typhoon track and moved to left in a few days. Using satellite data, in situ measurements and numerical modeling based on the East Asian Seas Nowcast/Forecast System (EASNFS), we performed detailed investigations. To obtain realistic typhoon-strength atmospheric forcing, the EASNFS applied typhoon-resolving Weather Research and Forecasting (WRF) model wind field blended with global weather forecast winds from the U.S. Navy Operational Global Atmospheric Prediction System (NOGAPS). In addition to the already known impacts from the slow typhoon translation speed and shallow pre-exiting ocean thermocline, we found the importance of the unique geographical setting of the SCS and the NE monsoon. As the event happened in late October, NE monsoon already started and contributed to the southwestward ambient surface current. Together with the topographicβ effect, the cold wake shifted westward to the left of Megi's track. It was also found that Megi expelled waters away from the SCS and manifested as a gush of internal Kelvin wave exporting waters through the Luzon Strait. The consequential sea level depression lasted and presented a favorable condition for cold dome development. Fission of the north-south elongated cold dome resulted afterward and produced two cold eddies that dissipated slowly thereafter.

Interaction between behavioral and pharmacological treatment strategies to decrease cocaine choice in rhesus monkeys.

PubMed

Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

2013-02-01

Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently, the FR response requirement for cocaine or food was varied (food, FR 100; cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine on cocaine vs food choice were redetermined. Decreases in the cocaine FR or increases in the food FR resulted in leftward shifts in the cocaine choice dose-effect curve, whereas increases in the cocaine FR or decreases in the food FR resulted in rightward shifts in the cocaine choice dose-effect curve. The efficacy of phenmetrazine to decrease cocaine choice varied systematically as a function of the prevailing response requirements, such that phenmetrazine efficacy was greatest when cocaine choice was maintained by relatively low unit cocaine doses. These results suggest that efficacy of pharmacotherapies to modulate cocaine use can be influenced by behavioral contingencies of cocaine availability. Agonist medications may be most effective under contingencies that engender choice of relatively low cocaine doses.

Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance.

PubMed

Fairbanks, C A; Wilcox, G L

1997-09-01

The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 degrees C) tail flick test in mice. Intrathecal pretreatment with morphine (40 nmol) produced a 9.6-fold rightward shift in the morphine dose-response curve. This shift confirmed the induction of acute spinal morphine tolerance. Intrathecal copretreatment with the receptor antagonists (competitive and noncompetitive, respectively) dizolcipine (MK801, 3 nmol) or LY235959 (4 pmol) and morphine [40 nmol, intrathecally (i.t.)] attenuated acute tolerance to morphine measured 8 hr later. A 60-min pretreatment of 7-nitroindazole (6 nmol, i.t.), a selective neuronal NOS inhibitor, followed by administration of morphine (40 nmol, i.t.) blocked the induction of morphine tolerance. Intrathecal copretreatment with morphine (40 nmol, i.t.) and agmatine (4 nmol, i.t.), an imidazoline, receptor agonist and putative nitric oxide synthase inhibitor, almost completely abolished acute spinal morphine tolerance. The results of these experiments agree with previous reports using models of chronically induced morphine tolerance. This evidence supports the proposal that the mechanisms responsible for acute morphine tolerance parallel those underlying chronic morphine tolerance. This study attests to the powerful predictive value of acute induction as a model for morphine tolerance.

Hypotensive effect of Gentiana floribunda is mediated through Ca++ antagonism pathway

PubMed Central

2012-01-01

Background Gentiana floribunda was investigated for the possible hypotensive and vasodilator activities in an attempt to rationalize its traditional use in hypertension. Methods The crude extract of Gentiana floribunda (Gf.Cr) was studied in anaesthetized rats and isolated thoracic aorta tissues. Results Gf.Cr which tested positive for presence of flavonoids, saponins, sterols, tannins and terpenes caused dose-dependent (3.0-100 mg/kg) fall in arterial blood pressure (BP) of rats under anaesthesia. In rat aortic ring preparations denuded of endothelium, Gf.Cr at concentration range of 1.0-10 mg/mL relaxed high K+ (80 mM) and phenylephrine (PE, 1 μM)-induced contractions and shifted Ca++ dose–response curves to right, similar to that caused by verapamil. It also suppressed PE (1 μM) control peak responses at 0.3-1.0 mg/mL, obtained in Ca++-free medium, as exhibited by verapamil. Pre-treatment of tissues with Gf.Cr produced rightward non-parallel shift of PE-curves with decline of maximum contractile response. The vasodilator effect of Gf.Cr was endothelial-independent, as it was not blocked by Nω-nitro-L-arginine methyl ester hydrochloride, atropine and indomethacin in endothelium-intact aortic tissues. Conclusions These data indicate that BP-lowering action of Gentiana floribunda occurred via Ca++ antagonism (inhibition of Ca++ ingress and release from intracellular stores), which provides pharmacological basis to justify its effectiveness in hypertension. PMID:22883710

New rules for visual selection: Isolating procedural attention.

PubMed

Ramamurthy, Mahalakshmi; Blaser, Erik

2017-02-01

High performance in well-practiced, everyday tasks-driving, sports, gaming-suggests a kind of procedural attention that can allocate processing resources to behaviorally relevant information in an unsupervised manner. Here we show that training can lead to a new, automatic attentional selection rule that operates in the absence of bottom-up, salience-driven triggers and willful top-down selection. Taking advantage of the fact that attention modulates motion aftereffects, observers were presented with a bivectorial display with overlapping, iso-salient red and green dot fields moving to the right and left, respectively, while distracted by a demanding auditory two-back memory task. Before training, since the motion vectors canceled each other out, no net motion aftereffect (MAE) was found. However, after 3 days (0.5 hr/day) of training, during which observers practiced selectively attending to the red, rightward field, a significant net MAE was observed-even when top-down selection was again distracted. Further experiments showed that these results were not due to perceptual learning, and that the new rule targeted the motion, and not the color of the target dot field, and global, not local, motion signals; thus, the new rule was: "select the rightward field." This study builds on recent work on selection history-driven and reward-driven biases, but uses a novel paradigm where the allocation of visual processing resources are measured passively, offline, and when the observer's ability to execute top-down selection is defeated.

NK-2 is the predominant tachykinin receptor subtype in the swine ureter.

PubMed

Jerde, T J; Saban, R; Bjorling, D E; Nakada, S Y

1999-02-01

To determine which of the known tachykinin receptor subtypes is predominant in the swine ureter. Ureters from adult pigs were harvested, cut into longitudinal strips and placed in 10 mL tissue baths containing Krebs buffer, under 4 g of initial tension. The magnitude and frequency of contractions were recorded. Tissues were incubated with 1 micromol/L solutions of peptidase inhibitors (phosphoramidon and captopril) for 1 h to inhibit degradation of peptides and treated with either CP 96,345 (NK-1 receptor antagonist), SR 48,968 (NK-2 receptor antagonist) or saline (control). Concentration-response curves to the tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were determined. Ureteric segments showed a concentration-dependent response to all tachykinins; NKA stimulated increased contractions at a lower concentration than either SP or NKB (P<0.05). This was reflected by the difference in the effective concentration required to obtain half the maximal response (EC50 ) for each of the peptides. The mean (sd) EC50 values were (micromol/L): NKA, 0.2 (0.02); SP, 3.5 (0.7); and NKB, 4.5 (1.7). In addition, the selective NK-2 antagonist (SR 48,968) significantly reduced contractile responses to all peptides, as indicated by a 10-fold rightward shift of the concentration-response curves (P<0. 05), whereas the NK-1 antagonist (CP 96,345) had no significant effect. These results indicate that NK-2 is the predominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical applications for the treatment of ureteric disease.

Perceptual asymmetries in greyscales: object-based versus space-based influences.

PubMed

Thomas, Nicole A; Elias, Lorin J

2012-05-01

Neurologically normal individuals exhibit leftward spatial biases, resulting from object- and space-based biases; however their relative contributions to the overall bias remain unknown. Relative position within the display has not often been considered, with similar spatial conditions being collapsed across. Study 1 used the greyscales task to investigate the influence of relative position and object- and space-based contributions. One image in each greyscale pair was shifted towards the left or the right. A leftward object-based bias moderated by a bias to the centre was expected. Results confirmed this as a left object-based bias occurred in the right visual field, where the left side of the greyscale pairs was located in the centre visual field. Further, only lower visual field images exhibited a significant left bias in the left visual field. The left bias was also stronger when images were partially overlapping in the right visual field, demonstrating the importance of examining proximity. The second study examined whether object-based biases were stronger when actual objects, with directional lighting biases, were used. Direction of luminosity was congruent or incongruent with spatial location. A stronger object-based bias emerged overall; however a leftward bias was seen in congruent conditions and a rightward bias was seen in incongruent conditions. In conditions with significant biases, the lower visual field image was chosen most often. Results show that object- and space-based biases both contribute; however stimulus type allows either space- or object-based biases to be stronger. A lower visual field bias also interacts with these biases, leading the left bias to be eliminated under certain conditions. The complex interaction occurring between frame of reference and visual field makes spatial location extremely important in determining the strength of the leftward bias. Copyright © 2010 Elsevier Srl. All rights reserved.

Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat.

PubMed

Alwasel, Saleh H; Ashton, Nick

2012-02-01

Hypertension and renal dysfunction can be programmed in the rat by prenatal exposure to a low-protein (LP) diet. Expression of the renal thick ascending limb (TAL) sodium transporter NKCC2 is up-regulated, which has been predicted to result in greater sodium reabsorption. However, we have shown that LP rats excrete more not less sodium. The aim of this study was to determine whether the increased abundance of sodium:potassium:chloride (Na(+):K(+):2Cl(-)) co-transporter (NKCC2) leads to enhanced sodium uptake by the TAL. Pregnant Wistar rats were fed a control (18%) or LP (9%) diet. Amiloride (AM), bendroflumethiazide (BF), and furosemide (FUR) were administered acutely to male offspring at 4 weeks of age. Fractional excretion of sodium (FE(Na)) was significantly greater in vehicle-infused LP rats (3.0 ± 0.3%) compared with controls (1.7 ± 0.5, P < 0.01). FE(Na) by the LP proximal tubule did not differ from controls, whereas FE(Na) by the distal tubule was significantly greater (P < 0.01). These differences were abolished by the administration of AM + BF (equivalent to the outflow from the TAL) and AM + BF + FUR (equivalent to the outflow from the proximal tubule), suggesting that the increase in NKCC2 expression was not functional. However, during acute salt loading, the LP rat pressure natriuresis curve was shifted rightward, implying that raised systemic blood pressure is required to match urinary sodium excretion with dietary intake. These data suggest that renal sodium handling is impaired in the LP rat but that this is not due to increased NKCC2 expression.

Prism Adaptation Alters Electrophysiological Markers of Attentional Processes in the Healthy Brain.

PubMed

Martín-Arévalo, Elisa; Laube, Inga; Koun, Eric; Farnè, Alessandro; Reilly, Karen T; Pisella, Laure

2016-01-20

Neglect patients typically show a rightward attentional orienting bias and a strong disengagement deficit, such that they are especially slow in responding to left-sided targets after right-sided cues (Posner et al., 1984). Prism adaptation (PA) can reduce diverse debilitating neglect symptoms and it has been hypothesized that PA's effects are so generalized that they might be mediated by attentional mechanisms (Pisella et al., 2006; Redding and Wallace, 2006). In neglect patients, performance on spatial attention tasks improves after rightward-deviating PA (Jacquin-Courtois et al., 2013). In contrast, in healthy subjects, although there is evidence that leftward-deviating PA induces neglect-like performance on some visuospatial tasks, behavioral studies of spatial attention tasks have mostly yielded negative results (Morris et al., 2004; Bultitude et al., 2013). We hypothesized that these negative behavioral findings might reflect the limitations of behavioral measures in healthy subjects. Here we exploited the sensitivity of event-related potentials to test the hypothesis that electrophysiological markers of attentional processes in the healthy human brain are affected by PA. Leftward-deviating PA generated asymmetries in attentional orienting (reflected in the cue-locked N1) and in attentional disengagement for invalidly cued left targets (reflected in the target-locked P1). This is the first electrophysiological demonstration that leftward-deviating PA in healthy subjects mimics attentional patterns typically seen in neglect patients. Significance statement: Prism adaptation (PA) is a promising tool for ameliorating many deficits in neglect patients and inducing neglect-like behavior in healthy subjects. The mechanisms underlying PA's effects are poorly understood but one hypothesis suggests that it acts by modulating attention. To date, however, there has been no successful demonstration of attentional modulation in healthy subjects. We provide the first electrophysiological evidence that PA acts on attention in healthy subjects by mimicking the attentional pattern typically reported in neglect patients: both a rightward attentional orienting bias (reflected in the cue-locked N1) and a deficit in attentional disengagement from the right hemispace (reflected in the target-locked P1). This study makes an important contribution to refining current models of the mechanisms underlying PA's cognitive effects. Copyright © 2016 the authors 0270-6474/16/361019-12$15.00/0.

Sustained Attention Training Reduces Spatial Bias in Parkinson's Disease: A Pilot Case Series

PubMed Central

DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas; Esterman, Michael; Pistorino, Laura; Cronin-Golomb, Alice

2016-01-01

Individuals with Parkinson’s disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD/2 RPD) performed a visual search task before and after one month of computer training. Before training, all participants showed a significant spatial bias and after training, all participants’ spatial bias was eliminated. PMID:26360648

Sustained attention training reduces spatial bias in Parkinson's disease: a pilot case series.

PubMed

DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas; Esterman, Michael; Pistorino, Laura; Cronin-Golomb, Alice

2016-01-01

Individuals with Parkinson's disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention, whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD, 2 RPD) performed a visual search task before and after 1 month of computer training. Before training, all participants showed a significant spatial bias and after training, all participants' spatial bias was eliminated.

Visual Network Asymmetry and Default Mode Network Function in ADHD: An fMRI Study

PubMed Central

Hale, T. Sigi; Kane, Andrea M.; Kaminsky, Olivia; Tung, Kelly L.; Wiley, Joshua F.; McGough, James J.; Loo, Sandra K.; Kaplan, Jonas T.

2014-01-01

Background: A growing body of research has identified abnormal visual information processing in attention-deficit hyperactivity disorder (ADHD). In particular, slow processing speed and increased reliance on visuo-perceptual strategies have become evident. Objective: The current study used recently developed fMRI methods to replicate and further examine abnormal rightward biased visual information processing in ADHD and to further characterize the nature of this effect; we tested its association with several large-scale distributed network systems. Method: We examined fMRI BOLD response during letter and location judgment tasks, and directly assessed visual network asymmetry and its association with large-scale networks using both a voxelwise and an averaged signal approach. Results: Initial within-group analyses revealed a pattern of left-lateralized visual cortical activity in controls but right-lateralized visual cortical activity in ADHD children. Direct analyses of visual network asymmetry confirmed atypical rightward bias in ADHD children compared to controls. This ADHD characteristic was atypically associated with reduced activation across several extra-visual networks, including the default mode network (DMN). We also found atypical associations between DMN activation and ADHD subjects’ inattentive symptoms and task performance. Conclusion: The current study demonstrated rightward VNA in ADHD during a simple letter discrimination task. This result adds an important novel consideration to the growing literature identifying abnormal visual processing in ADHD. We postulate that this characteristic reflects greater perceptual engagement of task-extraneous content, and that it may be a basic feature of less efficient top-down task-directed control over visual processing. We additionally argue that abnormal DMN function may contribute to this characteristic. PMID:25076915

Cortical preparatory activity: representation of movement or first cog in a dynamical machine?

PubMed Central

Churchland, MM; Cunningham, JP; Kaufman, MT; Ryu, SI; Shenoy, KV

2010-01-01

Summary The motor cortices are active during both movement and movement preparation. A common assumption is that preparatory activity constitutes a sub-threshold form of movement activity: a neuron active during rightwards movements becomes modestly active during preparation of a rightwards movement. We asked whether this pattern of activity is in fact observed. We found that it was not: at the level of a single neuron, preparatory tuning was weakly correlated with movement-period tuning. Yet somewhat paradoxically, preparatory tuning could be captured by a preferred direction in an abstract ‘space’ that described the population-level pattern of movement activity. In fact, this relationship accounted for preparatory responses better than did traditional tuning models. These results are expected if preparatory activity provides the initial state of a dynamical system whose evolution produces movement activity. Our results thus suggest that preparatory activity may not represent specific factors, and may instead play a more mechanistic role. PMID:21040842

Left neglect dyslexia and the effect of stimulus duration.

PubMed

Arduino, Lisa S; Vallar, Giuseppe; Burani, Cristina

2006-01-01

The present study investigated the effects of the duration of the stimulus on the reading performance of right-brain-damaged patients with left neglect dyslexia. Three Italian patients read aloud words and nonwords, under conditions of unlimited time of stimulus exposure and of timed presentation. In the untimed condition, the majority of the patients' errors involved the left side of the letter string (i.e., neglect dyslexia errors). Conversely, in the timed condition, although the overall level of performance decreased, errors were more evenly distributed across the whole letter string (i.e., visual - nonlateralized - errors). This reduction of neglect errors with a reduced time of presentation of the stimulus may reflect the read out of elements of the letter string from a preserved visual storage component, such as iconic memory. Conversely, a time-unlimited presentation of the stimulus may bring about the rightward bias that characterizes the performance of neglect patients, possibly by a capture of the patients' attention by the final (rightward) letters of the string.

Direction detection thresholds of passive self-motion in artistic gymnasts.

PubMed

Hartmann, Matthias; Haller, Katia; Moser, Ivan; Hossner, Ernst-Joachim; Mast, Fred W

2014-04-01

In this study, we compared direction detection thresholds of passive self-motion in the dark between artistic gymnasts and controls. Twenty-four professional female artistic gymnasts (ranging from 7 to 20 years) and age-matched controls were seated on a motion platform and asked to discriminate the direction of angular (yaw, pitch, roll) and linear (leftward-rightward) motion. Gymnasts showed lower thresholds for the linear leftward-rightward motion. Interestingly, there was no difference for the angular motions. These results show that the outstanding self-motion abilities in artistic gymnasts are not related to an overall higher sensitivity in self-motion perception. With respect to vestibular processing, our results suggest that gymnastic expertise is exclusively linked to superior interpretation of otolith signals when no change in canal signals is present. In addition, thresholds were overall lower for the older (14-20 years) than for the younger (7-13 years) participants, indicating the maturation of vestibular sensitivity from childhood to adolescence.

Observed ocean waves by tropical cyclones

NASA Astrophysics Data System (ADS)

Zhang, Lin; Oey, Leo

2017-04-01

Ocean waves produced by tropical cyclones (TC) modify air-sea fluxes which in turn are crucial to the storms' intensity and development, yet they are poorly understood. Here we use 24 years (1992-2015) of observed waves, winds and TC-track information to stratify storm-centered composite maps of waves and winds according to TC intensities and translation speeds (Uh). While the wind field is rightward-asymmetric independent of Uh, the wave field is rightward-symmetric in concert with the wind for slow-translating TCs (Uh ≤ 3 m s-1), but right-rear asymmetric with strongest waves in the 4th quadrant for medium to fast-translating TCs (3 < Uh ≤ 7 m s-1), especially for the very fast storms (Uh > 7 m s-1), all independent of TC-intensity. The dominance of the right-rear asymmetry for fast-translating TCs appears to be related to the development of cross swells as the storms move faster, but further research using models are needed to understand the physical mechanisms.

A matter of hand: Causal links between hand dominance, structural organization of fronto-parietal attention networks, and variability in behavioural responses to transcranial magnetic stimulation.

PubMed

Cazzoli, Dario; Chechlacz, Magdalena

2017-01-01

Considerable evidence suggests that, on a group level, human visuospatial attention is asymmetrically organized, with a right-hemispheric dominance. The asymmetrical organization of the superior longitudinal fasciculus (SLF) has been shown to account for the right-hemispheric dominance in visual attention. However, such account is by no means universal, and large individual differences in asymmetrical performance on visuospatial tasks have been reported. Furthermore, the variability in the SLF lateralization has been shown to correlate with behavioural asymmetries. Continuous theta burst stimulation (cTBS) enables to temporarily interfere with cortical activity. cTBS applied over the posterior parietal cortex (PPC) has been previously used to systematically study attentional asymmetries. Interestingly, large individual differences in the effectiveness of stimulation have been reported. In accordance with earlier both animal and human studies, one possible cause underlying these striking individual differences might lie in the structural organization of frontoparietal pathways subserving visuospatial attention. Thus, the current study employed diffusion tractography to examine the relationship between the variability in the structural organization of the SLF and the individual differences in attentional shifts induced by a modified cTBS (cTBS mod ; triplets of pulses at 30 Hz, repeated at 6 Hz) applied over the IPS, as measured by a line bisection task. Consistent with previous studies, on a group level, cTBS mod applied over the right intraparietal sulcus (IPS) triggered a rightward bisection bias shift, and there were no significant effects of cTBS mod applied over the left IPS. However, further analyses demonstrated that both handedness and structural variability (as assessed based on hindrance modulated orientational anisotropy) within the middle and the ventral branches of the SLF predicted individual differences in the cTBS mod -induced attentional shifts. Our study thus suggests that the effects of cTBS mod over the IPS may depend on intra-hemispheric interactions between cortical loci controlling visual attention. To conclude, our findings provide converging evidence for the notion put forward previously that inter-individual variability in the structural organization of intra-hemispheric frontoparietal connections has important implications for the functional models of human visual attention. Moreover, we hypothesize that this may also be relevant for the understanding of attentional disorders and their rehabilitation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Body-Specific Representations of Spatial Location

ERIC Educational Resources Information Center

Brunye, Tad T.; Gardony, Aaron; Mahoney, Caroline R.; Taylor, Holly A.

2012-01-01

The body specificity hypothesis (Casasanto, 2009) posits that the way in which people interact with the world affects their mental representation of information. For instance, right- versus left-handedness affects the mental representation of affective valence, with right-handers categorically associating good with rightward areas and bad with…

Effect of aging and direction of impulse in video head impulse test.

PubMed

Kim, Tae Hwan; Kim, Min-Beom

2017-09-12

The aim of this study was to identify the difference of gain value in the video head impulse test (vHIT) according to the age of the patient and the direction of the impulse. All participants were subjected to vHIT with horizontal semicircular canal (HSCC). vHIT with vertical canal (posterior and anterior semicircular canal [PSCC and ASCC]) additionally was performed in 434 participants. The mean vestibulo-ocular reflex (VOR) gain was maintained in patients in the HSCC at below 70 years (1.025 ± 0.08) and in the vertical canal at below 80 years (PSCC: 0.965 ± 0.12, ASCC: 0.975 ± 0.14). However, the decrease of VOR gain was significant in patients over 70 years in the HSCC (0.978 ± 0.35, P < .001) and in patients over 80 years in the vertical canal (PSCC: 0.828 ± 0.16, ASCC: 0.851 ± 0.13, P < .001). In addition, a VOR gain of rightward impulse was higher than the leftward impulse, but there was no difference based on the direction of impulse in the vertical impulse test. VOR gain declines with increasing age, over 70 years on the horizontal canal, and over 80 years on the vertical canal. Additionally, horizontal VOR gain of rightward impulse was higher than the leftward impulse in right-eye recordings only, but the vertical canal showed no difference of gain according to the direction of impulse. 2b. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Cloning, functional expression, and characterization of a PKA-activated gastric Cl- channel.

PubMed

Malinowska, D H; Kupert, E Y; Bahinski, A; Sherry, A M; Cuppoletti, J

1995-01-01

cDNA encoding a Cl- channel was isolated from a rabbit gastric library, sequenced, and expressed in Xenopus oocytes. The predicted protein (898 amino acids, relative molecular mass 98,433 Da) was overall 93% similar to the rat brain ClC-2 Cl- channel. However, a 151-amino acid stretch toward the COOH-terminus was 74% similar to ClC-2 with six amino acids deleted. Two new potential protein kinase A (PKA) phosphorylation sites (also protein kinase C phosphorylation sites) were introduced. cRNA-injected Xenopus oocytes expressed a Cl- channel that was active at pHtrans 3 and had a linear current-voltage (I-V) curve and a slope conductance of 29 +/- 1 pS at 800 mM CsCl. A fivefold Cl- gradient caused a rightward shift in the I-V curve with a reversal potential of +30 +/- 3 mV, indicating anion selectivity. The selectivity was I- > Cl- > NO3-. The native and recombinant Cl- channel were both activated in vitro by PKA catalytic subunit and ATP. The electrophysiological and regulatory properties of the cloned and the native channel were similar. The cloned protein may be the Cl- channel involved in gastric HCl secretion.

Ocean response to typhoons in the western North Pacific: Composite results from Argo data

NASA Astrophysics Data System (ADS)

Lin, Sheng; Zhang, Wen-Zhou; Shang, Shao-Ping; Hong, Hua-Sheng

2017-05-01

Composite structures of ocean temperature and salinity anomalies caused by tropical cyclones (TCs) or typhoons in the western North Pacific Ocean were obtained from Argo data. These structures were used to analyze ocean responses to typhoons and the dynamic mechanisms inherent in those responses with a particular focus on upwelling. TC-induced cooling is often strongly rightward-biased in the surface layer, and shifts toward the typhoon track at depths exceeding roughly 100 m. In the central water column within approximately 75 km of the typhoon track, subsurface warming predicted by vertical mixing is restrained and replaced by cooling due to upwelling. Upwelling contributes 15% on average to temperature cooling in the near surface layer (10-30 m), 84% in the subsurface layer (30-250 m) and 94% in the deep layer (250-600 m) during the period of 0.5-2.5 days after the typhoon's passage. It is suggested that the sea surface cooling effect of vertical mixing can be enhanced by the upwelling. The effect of upwelling is also prominent in the salinity response to typhoons. The composite results from the Argo data clearly reveal basic ocean responses to typhoons and indicate the important role of upwelling therein.

Modeling systolic pressure variation due to positive pressure ventilation.

PubMed

Messerges, Joanne

2006-01-01

Although many clinical techniques have been proposed to assess blood volume none have been established as an undisputed standard practice, Volume studies suggest systolic pressure variation (SPV) as a promising volume indicator but underlying influences on SPV are not well understood. Successful modeling of SPV will reveal the major SPV influencers, guide algorithm development to accommodate these influencers, and potentially lead to a more clinically relevant interpretation of SPV values, thus improving upon current clinical methods for assessing blood volume. This study takes a first step towards identifying SPV influencers by investigating three variations of an existing pressure-flow cardiovascular model. Each successive version introduces an additional modification in attempt to model SPV under normovolemic and hypovolemic conditions, where the last model accounts for positive pressure ventilation, venous compression, and a rightward septum shift. Under normovolemic conditions, each model yields SPV values of 5.8, 6.4, and 6.7 mmHg, respectively. Under hypovolemic conditions the results do not agree with clinical findings, suggesting these three mechanisms alone do not dictate the clinical SPV response to a decrease in volume. Model results are used to suggest improvements for future work.

Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine.

PubMed

Zhang, Fan; Cheng, Yanxin; Li, Hong; Jia, Qingzhong; Zhang, Hailin; Zhao, Senming

2015-01-01

Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures. A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons. Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential. Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents. © 2015 S. Karger AG, Basel.

External Barium Affects the Gating of KCNQ1 Potassium Channels and Produces a Pore Block via Two Discrete Sites

PubMed Central

Gibor, Gilad; Yakubovich, Daniel; Peretz, Asher; Attali, Bernard

2004-01-01

The pore properties and the reciprocal interactions between permeant ions and the gating of KCNQ channels are poorly understood. Here we used external barium to investigate the permeation characteristics of homomeric KCNQ1 channels. We assessed the Ba2+ binding kinetics and the concentration and voltage dependence of Ba2+ steady-state block. Our results indicate that extracellular Ba2+ exerts a series of complex effects, including a voltage-dependent pore blockade as well as unique gating alterations. External barium interacts with the permeation pathway of KCNQ1 at two discrete and nonsequential sites. (a) A slow deep Ba2+ site that occludes the channel pore and could be simulated by a model of voltage-dependent block. (b) A fast superficial Ba2+ site that barely contributes to channel block and mostly affects channel gating by shifting rightward the voltage dependence of activation, slowing activation, speeding up deactivation kinetics, and inhibiting channel inactivation. A model of voltage-dependent block cannot predict the complex impact of Ba2+ on channel gating in low external K+ solutions. Ba2+ binding to this superficial site likely modifies the gating transitions states of KCNQ1. Both sites appear to reside in the permeation pathway as high external K+ attenuates Ba2+ inhibition of channel conductance and abolishes its impact on channel gating. Our data suggest that despite the high degree of homology of the pore region among the various K+ channels, KCNQ1 channels display significant structural and functional uniqueness. PMID:15226366

Handedness Shapes Children's Abstract Concepts

ERIC Educational Resources Information Center

Casasanto, Daniel; Henetz, Tania

2012-01-01

Can children's handedness influence how they represent abstract concepts like "kindness" and "intelligence"? Here we show that from an early age, right-handers associate rightward space more strongly with positive ideas and leftward space with negative ideas, but the opposite is true for left-handers. In one experiment, children indicated where on…

Effect of Auditory Motion Velocity on Reaction Time and Cortical Processes

ERIC Educational Resources Information Center

Getzmann, Stephan

2009-01-01

The study investigated the processing of sound motion, employing a psychophysical motion discrimination task in combination with electroencephalography. Following stationary auditory stimulation from a central space position, the onset of left- and rightward motion elicited a specific cortical response that was lateralized to the hemisphere…

Atypical Alpha Asymmetry in Adults with ADHD

ERIC Educational Resources Information Center

Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

2009-01-01

Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

Scene Configuration and Object Reliability Affect the Use of Allocentric Information for Memory-Guided Reaching

PubMed Central

Klinghammer, Mathias; Blohm, Gunnar; Fiehler, Katja

2017-01-01

Previous research has shown that egocentric and allocentric information is used for coding target locations for memory-guided reaching movements. Especially, task-relevance determines the use of objects as allocentric cues. Here, we investigated the influence of scene configuration and object reliability as a function of task-relevance on allocentric coding for memory-guided reaching. For that purpose, we presented participants images of a naturalistic breakfast scene with five objects on a table and six objects in the background. Six of these objects served as potential reach-targets (= task-relevant objects). Participants explored the scene and after a short delay, a test scene appeared with one of the task-relevant objects missing, indicating the location of the reach target. After the test scene vanished, participants performed a memory-guided reaching movement toward the target location. Besides removing one object from the test scene, we also shifted the remaining task-relevant and/or task-irrelevant objects left- or rightwards either coherently in the same direction or incoherently in opposite directions. By varying object coherence, we manipulated the reliability of task-relevant and task-irrelevant objects in the scene. In order to examine the influence of scene configuration (distributed vs. grouped arrangement of task-relevant objects) on allocentric coding, we compared the present data with our previously published data set (Klinghammer et al., 2015). We found that reaching errors systematically deviated in the direction of object shifts, but only when the objects were task-relevant and their reliability was high. However, this effect was substantially reduced when task-relevant objects were distributed across the scene leading to a larger target-cue distance compared to a grouped configuration. No deviations of reach endpoints were observed in conditions with shifts of only task-irrelevant objects or with low object reliability irrespective of task-relevancy. Moreover, when solely task-relevant objects were shifted incoherently, the variability of reaching endpoints increased compared to coherent shifts of task-relevant objects. Our results suggest that the use of allocentric information for coding targets for memory-guided reaching depends on the scene configuration, in particular the average distance of the reach target to task-relevant objects, and the reliability of task-relevant allocentric information. PMID:28450826

Scene Configuration and Object Reliability Affect the Use of Allocentric Information for Memory-Guided Reaching.

PubMed

Klinghammer, Mathias; Blohm, Gunnar; Fiehler, Katja

2017-01-01

Previous research has shown that egocentric and allocentric information is used for coding target locations for memory-guided reaching movements. Especially, task-relevance determines the use of objects as allocentric cues. Here, we investigated the influence of scene configuration and object reliability as a function of task-relevance on allocentric coding for memory-guided reaching. For that purpose, we presented participants images of a naturalistic breakfast scene with five objects on a table and six objects in the background. Six of these objects served as potential reach-targets (= task-relevant objects). Participants explored the scene and after a short delay, a test scene appeared with one of the task-relevant objects missing, indicating the location of the reach target. After the test scene vanished, participants performed a memory-guided reaching movement toward the target location. Besides removing one object from the test scene, we also shifted the remaining task-relevant and/or task-irrelevant objects left- or rightwards either coherently in the same direction or incoherently in opposite directions. By varying object coherence, we manipulated the reliability of task-relevant and task-irrelevant objects in the scene. In order to examine the influence of scene configuration (distributed vs. grouped arrangement of task-relevant objects) on allocentric coding, we compared the present data with our previously published data set (Klinghammer et al., 2015). We found that reaching errors systematically deviated in the direction of object shifts, but only when the objects were task-relevant and their reliability was high. However, this effect was substantially reduced when task-relevant objects were distributed across the scene leading to a larger target-cue distance compared to a grouped configuration. No deviations of reach endpoints were observed in conditions with shifts of only task-irrelevant objects or with low object reliability irrespective of task-relevancy. Moreover, when solely task-relevant objects were shifted incoherently, the variability of reaching endpoints increased compared to coherent shifts of task-relevant objects. Our results suggest that the use of allocentric information for coding targets for memory-guided reaching depends on the scene configuration, in particular the average distance of the reach target to task-relevant objects, and the reliability of task-relevant allocentric information.

Task activation and functional connectivity show concordant memory laterality in temporal lobe epilepsy.

PubMed

Sideman, Noah; Chaitanya, Ganne; He, Xiaosong; Doucet, Gaelle; Kim, Na Young; Sperling, Michael R; Sharan, Ashwini D; Tracy, Joseph I

2018-04-01

In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures. A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures. Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres. Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several different phenotypes, varying according to side of seizure onset and the specific mesial structures involved. There is good correspondence between task LI activation and FC patterns in the setting of LTLE, suggesting that reliable visual episodic memory reorganization may require both a shift in nodal activation and a change in nodal connectivity with mesial temporal structures involved in memory. Copyright © 2018. Published by Elsevier Inc.

Rightward Collisions and Their Association with Pseudoneglect

ERIC Educational Resources Information Center

Nicholls, Michael E. R.; Loftus, Andrea M.; Orr, Catherine A.; Barre, Natalie

2008-01-01

Whereas right parietal damage can result in left hemineglect, the general population shows a subtle neglect of the right hemispace--known as pseudoneglect. A recent study has demonstrated that people collide to the right more often and attributed this bias to pseudoneglect. [Nicholls, M. E. R., Loftus, A., Meyer, K., & Mattingley, J.B. (2007).…

Decreased Leftward ‘Aiming’ Motor-Intentional Spatial Cuing in Traumatic Brain Injury

PubMed Central

Wagner, Daymond; Eslinger, Paul J.; Barrett, A. M.

2016-01-01

Objective To characterize the mediation of attention and action in space following traumatic brain injury (TBI). Method Two exploratory analyses were performed to determine the influence of spatial ‘Aiming’ motor versus spatial ‘Where’ bias on line bisection in TBI participants. The first experiment compared performance according to severity and location of injury in TBI. The second experiment examined bisection performance in a larger TBI sample against a matched control group. In both experiments, participants bisected lines in near and far space using an apparatus that allowed for the fractionation of spatial Aiming versus Where error components. Results In the first experiment, participants with severe injuries tended to incur rightward error when starting from the right in far space, compared with participants with mild injuries. In the second experiment, when performance was examined at the individual level, more participants with TBI tended to incur rightward motor error compared to controls. Conclusions TBI may cause frontal-subcortical cognitive dysfunction and asymmetric motor perseveration, affecting spatial Aiming bias on line bisection. Potential effects on real-world function need further investigation. PMID:27571220

Right-hemispheric dominance for visual remapping in humans.

PubMed

Pisella, L; Alahyane, N; Blangero, A; Thery, F; Blanc, S; Pelisson, D

2011-02-27

We review evidence showing a right-hemispheric dominance for visuo-spatial processing and representation in humans. Accordingly, visual disorganization symptoms (intuitively related to remapping impairments) are observed in both neglect and constructional apraxia. More specifically, we review findings from the intervening saccade paradigm in humans--and present additional original data--which suggest a specific role of the asymmetrical network at the temporo-parietal junction (TPJ) in the right hemisphere in visual remapping: following damage to the right dorsal posterior parietal cortex (PPC) as well as part of the corpus callosum connecting the PPC to the frontal lobes, patient OK in a double-step saccadic task exhibited an impairment when the second saccade had to be directed rightward. This singular and lateralized deficit cannot result solely from the patient's cortical lesion and, therefore, we propose that it is due to his callosal lesion that may specifically interrupt the interhemispheric transfer of information necessary to execute accurate rightward saccades towards a remapped target location. This suggests a specialized right-hemispheric network for visuo-spatial remapping that subsequently transfers target location information to downstream planning regions, which are symmetrically organized.

Bidirectional semantic associations between social power and weight.

PubMed

He, Xiaoling; Chen, Jun; Li, Jianan

2018-02-01

Two experiments were conducted to examine bidirectional semantic associations between power and weight using a priming paradigm. Bidirectionality in the relationship between power and weight was demonstrated, utilising tasks that were identical except that the orders in which the stimuli were presented were reversed. In Experiment 1, an empty scale leaning either leftward or rightward was used as a priming stimulus, and a scale that appeared in equilibrium with a pair of power words was used as a target stimulus. In Experiment 2, a scale with a pair of words that appeared in equilibrium was used as a priming stimulus, and an empty scale leaning either leftward or rightward was used as a target stimulus. We identified interaction effects between power and weight in both experiments. Associations between power and weight provide evidence for both conceptual metaphor views and evolutionary theory. The bidirectionality of metaphorical effects is in line with the strong version of metaphoric structuring. Both language and experiential correlations play important roles in the development of the mapping between power and weight. © 2016 International Union of Psychological Science.

Embodiment of abstract concepts: good and bad in right- and left-handers.

PubMed

Casasanto, Daniel

2009-08-01

Do people with different kinds of bodies think differently? According to the body-specificity hypothesis, people who interact with their physical environments in systematically different ways should form correspondingly different mental representations. In a test of this hypothesis, 5 experiments investigated links between handedness and the mental representation of abstract concepts with positive or negative valence (e.g., honesty, sadness, intelligence). Mappings from spatial location to emotional valence differed between right- and left-handed participants. Right-handers tended to associate rightward space with positive ideas and leftward space with negative ideas, but left-handers showed the opposite pattern, associating rightward space with negative ideas and leftward with positive ideas. These contrasting mental metaphors for valence cannot be attributed to linguistic experience, because idioms in English associate good with right but not with left. Rather, right- and left-handers implicitly associated positive valence more strongly with the side of space on which they could act more fluently with their dominant hands. These results support the body-specificity hypothesis and provide evidence for the perceptuomotor basis of even the most abstract ideas.

Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas

PubMed Central

Navari, Mohsen; Etebari, Maryam; Ibrahimi, Mostafa; Leoncini, Lorenzo

2018-01-01

Epstein–Barr virus (EBV) is a human γ-herpesvirus implicated in several human malignancies, including a wide range of lymphomas. Several molecules encoded by EBV in its latent state are believed to be related to EBV-induced lymphomagenesis, among which microRNAs—small RNAs with a posttranscriptional regulating role—are of great importance. The genome of EBV encodes 44 mature microRNAs belonging to two different classes, including BamHI-A rightward transcript (BART) and Bam HI fragment H rightward open reading frame 1 (BHRF1), with different expression levels in different EBV latency types. These microRNAs might contribute to the pathogenetic effects exerted by EBV through targeting self mRNAs and host mRNAs and interfering with several important cellular mechanisms such as immunosurveillance, cell proliferation, and apoptosis. In addition, EBV microRNAs can regulate the surrounding microenvironment of the infected cells through exosomal transportation. Moreover, these small molecules could be potentially used as molecular markers. In this review, we try to present an updated and extensive view of the role of EBV-encoded miRNAs in human lymphomas. PMID:29649101

Right-hemispheric dominance for visual remapping in humans

PubMed Central

Pisella, L.; Alahyane, N.; Blangero, A.; Thery, F.; Blanc, S.; Pelisson, D.

2011-01-01

We review evidence showing a right-hemispheric dominance for visuo-spatial processing and representation in humans. Accordingly, visual disorganization symptoms (intuitively related to remapping impairments) are observed in both neglect and constructional apraxia. More specifically, we review findings from the intervening saccade paradigm in humans—and present additional original data—which suggest a specific role of the asymmetrical network at the temporo-parietal junction (TPJ) in the right hemisphere in visual remapping: following damage to the right dorsal posterior parietal cortex (PPC) as well as part of the corpus callosum connecting the PPC to the frontal lobes, patient OK in a double-step saccadic task exhibited an impairment when the second saccade had to be directed rightward. This singular and lateralized deficit cannot result solely from the patient's cortical lesion and, therefore, we propose that it is due to his callosal lesion that may specifically interrupt the interhemispheric transfer of information necessary to execute accurate rightward saccades towards a remapped target location. This suggests a specialized right-hemispheric network for visuo-spatial remapping that subsequently transfers target location information to downstream planning regions, which are symmetrically organized. PMID:21242144

Neural correlates of visuospatial bias in patients with left hemisphere stroke: a causal functional contribution analysis based on game theory.

PubMed

Malherbe, C; Umarova, R M; Zavaglia, M; Kaller, C P; Beume, L; Thomalla, G; Weiller, C; Hilgetag, C C

2017-10-12

Stroke patients frequently display spatial neglect, an inability to report, or respond to, relevant stimuli in the contralesional space. Although this syndrome is widely considered to result from the dysfunction of a large-scale attention network, the individual contributions of damaged grey and white matter regions to neglect are still being disputed. Moreover, while the neuroanatomy of neglect in right hemispheric lesions is well studied, the contributions of left hemispheric brain regions to visuospatial processing are less well understood. To address this question, 128 left hemisphere acute stroke patients were investigated with respect to left- and rightward spatial biases measured as severity of deviation in the line bisection test and as Center of Cancellation (CoC) in the Bells Test. Causal functional contributions and interactions of nine predefined grey and white matter regions of interest in visuospatial processing were assessed using Multi-perturbation Shapley value Analysis (MSA). MSA, an inference approach based on game theory, constitutes a robust and exact multivariate mathematical method for inferring functional contributions from multi-lesion patterns. According to the analysis of performance in the Bells test, leftward attentional bias (contralesional deficit) was associated with contributions of the left superior temporal gyrus and rightward attentional bias with contributions of the left inferior parietal lobe, whereas the arcuate fascicle was contributed to both contra- and ipsilesional bias. Leftward and rightward deviations in the line bisection test were related to contributions of the superior longitudinal fascicle and the inferior parietal lobe, correspondingly. Thus, Bells test and line bisection tests, as well as ipsi- and contralesional attentional biases in these tests, have distinct neural correlates. Our findings demonstrate the contribution of different grey and white matter structures to contra- and ipsilesional spatial biases as revealed by left hemisphere stroke. The results provide new insights into the role of the left hemisphere in visuospatial processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Visual and tactile length matching in spatial neglect.

PubMed

Bisiach, Edoardo; McIntosh, Robert D; Dijkerman, H Chris; McClements, Kevin I; Colombo, Mariarosa; Milner, A David

2004-01-01

Previous studies have shown that many patients with spatial neglect underestimate the horizontal extent of leftwardly located shapes (presented on screen or on paper) relative to rightwardly located shapes. This has been used to help explain their leftward biases in line bisection. In the present study we have tested patients with right hemisphere damage, either with or without neglect, on a comparable length matching task, but using 3-dimensional objects. The task was executed first visually without tactile contact, and second through touch without vision. In both sense modalities, we found that patients with neglect, but not those without, tended to underestimate leftward located objects relative to rightward located objects, differing significantly in this regard from healthy subjects. However these lateral biases were not as frequent or as pronounced as in previous studies using 2-D visual shapes. Despite the similar asymmetries in the two sense modalities, we found only a small correlation between them, and clear double dissociations were observed among our patients. We conclude that leftward length underestimation cannot be attributed to any one single cause. First it cannot be entirely due to impairments in the visual pathways, such as hemianopia and/or processing biases, since the disorder is also seen in the tactile modality. At the same time, however, length underestimation phenomena cannot be fully explained as a disruption of a supramodal central size processor, since they can occur in either vision or touch alone. Our data would fit best with a multiple-factor model in which some patients show leftward length underestimation for modality-specific reasons, while others do so due to a more high-level disruption of size judgements.

Right Visual Field Advantage for Perceived Contrast: Correlation with an Auditory Bias and Handedness

ERIC Educational Resources Information Center

Railo, H.; Tallus, J.; Hamalainen, H.

2011-01-01

Studies have suggested that supramodal attentional resources are biased rightward due to asymmetric spatial fields of the two hemispheres. This bias has been observed especially in right-handed subjects. We presented left and right-handed subjects with brief uniform grey visual stimuli in either the left or right visual hemifield. Consistent with…

Young Infants Detect the Direction of Biological Motion in Point-Light Displays

ERIC Educational Resources Information Center

Kuhlmeier, Valerie A.; Troje, Nikolaus F.; Lee, Vivian

2010-01-01

In the present study, we examined if young infants can extract information regarding the directionality of biological motion. We report that 6-month-old infants can differentiate leftward and rightward motions from a movie depicting the sagittal view of an upright human point-light walker, walking as if on a treadmill. Inversion of the stimuli…

Rightward Biases in Free-Viewing Visual Bisection Tasks: Implications for Leftward Responses Biases on Similar Tasks

ERIC Educational Resources Information Center

Elias, Lorin J.; Robinson, Brent; Saucier, Deborah M.

2005-01-01

Neurologically normal individuals exhibit strong leftward response biases during free-viewing perceptual judgments of brightness, quantity, and size. When participants view two mirror-reversed objects and they are forced to choose which object appears darker, more numerous, or larger, the stimulus with the relevant feature on the left side is…

Interlateral Asymmetry in the Time Course of the Effect of a Peripheral Prime Stimulus

ERIC Educational Resources Information Center

Castro-Barros, B. A.; Righi, L. L.; Grechi, G.; Ribeiro-do-Valle, L. E.

2008-01-01

Evidence exists that both right and left hemisphere attentional mechanisms are mobilized when attention is directed to the right visual hemifield and only right hemisphere attentional mechanisms are mobilized when attention is directed to the left visual hemifield. This arrangement might lead to a rightward bias of automatic attention. The…

Look over There! Unilateral Gaze Increases Geographical Memory of the 50 United States

ERIC Educational Resources Information Center

Propper, Ruth E.; Brunye, Tad T.; Christman, Stephen D.; Januszewskia, Ashley

2012-01-01

Based on their specialized processing abilities, the left and right hemispheres of the brain may not contribute equally to recall of general world knowledge. US college students recalled the verbal names and spatial locations of the 50 US states while sustaining leftward or rightward unilateral gaze, a procedure that selectively activates the…

Gravitoinertial force magnitude and direction influence head-centric auditory localization

NASA Technical Reports Server (NTRS)

DiZio, P.; Held, R.; Lackner, J. R.; Shinn-Cunningham, B.; Durlach, N.

2001-01-01

We measured the influence of gravitoinertial force (GIF) magnitude and direction on head-centric auditory localization to determine whether a true audiogravic illusion exists. In experiment 1, supine subjects adjusted computer-generated dichotic stimuli until they heard a fused sound straight ahead in the midsagittal plane of the head under a variety of GIF conditions generated in a slow-rotation room. The dichotic stimuli were constructed by convolving broadband noise with head-related transfer function pairs that model the acoustic filtering at the listener's ears. These stimuli give rise to the perception of externally localized sounds. When the GIF was increased from 1 to 2 g and rotated 60 degrees rightward relative to the head and body, subjects on average set an acoustic stimulus 7.3 degrees right of their head's median plane to hear it as straight ahead. When the GIF was doubled and rotated 60 degrees leftward, subjects set the sound 6.8 degrees leftward of baseline values to hear it as centered. In experiment 2, increasing the GIF in the median plane of the supine body to 2 g did not influence auditory localization. In experiment 3, tilts up to 75 degrees of the supine body relative to the normal 1 g GIF led to small shifts, 1--2 degrees, of auditory setting toward the up ear to maintain a head-centered sound localization. These results show that head-centric auditory localization is affected by azimuthal rotation and increase in magnitude of the GIF and demonstrate that an audiogravic illusion exists. Sound localization is shifted in the direction opposite GIF rotation by an amount related to the magnitude of the GIF and its angular deviation relative to the median plane.

The statistical mechanics of human weight change

PubMed Central

2017-01-01

Over the past 35 years there has been a near doubling in the worldwide prevalence of obesity. Body Mass Index (BMI) distributions in high-income societies have increasingly shifted rightwards, corresponding to increases in average BMI that are due to well-studied changes in the socioeconomic environment. However, in addition to this shift, BMI distributions have also shown marked changes in their particular shape over time, exhibiting an ongoing right-skewed broadening that is not well understood. Here, we compile and analyze the largest data set so far of year-over-year BMI changes. The data confirm that, on average, heavy individuals become lighter while light individuals become heavier year-over-year, and also show that year-over-year BMI evolution is characterized by fluctuations with a magnitude that is linearly proportional to BMI. We find that the distribution of human BMIs is intrinsically dynamic—due to the short-term variability of human weight—and its shape is determined by a balance between deterministic drift towards a natural set point and diffusion resulting from random fluctuations in, e.g., diet and physical activity. We formulate a stochastic mathematical model for BMI dynamics, deriving a theoretical shape for the BMI distribution and offering a mechanism that may explain the right-skewed broadening of BMI distributions over time. An extension of the base model investigates the hypothesis that peer-to-peer social influence plays a role in BMI dynamics. While including this effect improves the fit with the data, indicating that correlations in the behavior of individuals with similar BMI may be important for BMI dynamics, testing social transmission against other plausible unmodeled effects and interpretations remains the subject of future work. Implications of our findings on the dynamics of BMI distributions for public health interventions are discussed. PMID:29253025

Cerebellar cathodal tDCS interferes with recalibration and spatial realignment during prism adaptation procedure in healthy subjects.

PubMed

Panico, Francesco; Sagliano, Laura; Grossi, Dario; Trojano, Luigi

2016-06-01

The aim of this study is to clarify the specific role of the cerebellum during prism adaptation procedure (PAP), considering its involvement in early prism exposure (i.e., in the recalibration process) and in post-exposure phase (i.e., in the after-effect, related to spatial realignment). For this purpose we interfered with cerebellar activity by means of cathodal transcranial direct current stimulation (tDCS), while young healthy individuals were asked to perform a pointing task on a touch screen before, during and after wearing base-left prism glasses. The distance from the target dot in each trial (in terms of pixels) on horizontal and vertical axes was recorded and served as an index of accuracy. Results on horizontal axis, that was shifted by prism glasses, revealed that participants who received cathodal stimulation showed increased rightward deviation from the actual position of the target while wearing prisms and a larger leftward deviation from the target after prisms removal. Results on vertical axis, in which no shift was induced, revealed a general trend in the two groups to improve accuracy through the different phases of the task, and a trend, more visible in cathodal stimulated participants, to worsen accuracy from the first to the last movements in each phase. Data on horizontal axis allow to confirm that the cerebellum is involved in all stages of PAP, contributing to early strategic recalibration process, as well as to spatial realignment. On vertical axis, the improving performance across the different stages of the task and the worsening accuracy within each task phase can be ascribed, respectively, to a learning process and to the task-related fatigue. Copyright © 2016 Elsevier Inc. All rights reserved.

Simultaneous cerebrovascular and cardiovascular responses during presyncope

NASA Technical Reports Server (NTRS)

Bondar, R. L.; Kassam, M. S.; Stein, F.; Dunphy, P. T.; Fortney, S.; Riedesel, M. L.

1995-01-01

BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve. METHODS: Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14% of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation mechanism.

Distinct Contributions of Dopamine in the Dorsolateral Striatum and Nucleus Accumbens Shell to the Reinforcing Properties of Cocaine

PubMed Central

Veeneman, Maartje M J; Broekhoven, Mark H; Damsteegt, Ruth; Vanderschuren, Louk J M J

2012-01-01

Dopaminergic neurotransmission in the dorsal and ventral striatum is thought to be involved in distinct aspects of cocaine addiction. Ventral striatal dopamine mediates the acute reinforcing properties of cocaine, whereas dopamine in the dorsolateral striatum (DLS) is thought to become involved in later stages of the addiction process to mediate well-established cue-controlled drug seeking. However, it is unclear whether the DLS also has a role in the reinforcing properties of cocaine itself. Therefore, we systematically investigated the involvement of dopamine in dorsal and ventral striatal regions in cocaine self-administration, using various schedules of reinforcement in animals with limited drug taking experience. Intra-DLS infusion of the dopamine receptor antagonist α-flupenthixol did not affect the acquisition of cocaine self-administration, increased cocaine self-administration under a fixed ratio-1 (FR-1) schedule of reinforcement, caused a rightward and downward shift of the dose–response curve of cocaine under an FR-1 schedule of reinforcement and decreased responding for cocaine under a progressive ratio (PR) schedule of reinforcement. Infusion of α-flupenthixol into the ventral nucleus accumbens (NAcc) shell inhibited the acquisition of cocaine self-administration, reduced responding for the drug under FR-1 and PR schedules of reinforcement, and caused a downward shift of the dose–response curve of cocaine self-administration under an FR-1 schedule of reinforcement. These data show that dopamine in both the DLS and NAcc shell is involved in cocaine reinforcement. We suggest that the DLS and the NAcc shell mediate somewhat distinct facets of the reinforcing properties of cocaine, related to its rewarding and motivational aspects, respectively. PMID:21918505

Growth and psychomotor development of patients with Duchenne muscular dystrophy.

PubMed

Sarrazin, Elisabeth; von der Hagen, Maja; Schara, Ulrike; von Au, Katja; Kaindl, Angela M

2014-01-01

Duchenne muscular dystrophy (DMD) is one of the most common hereditary degenerative neuromuscular diseases and caused by mutations in the dystrophin gene. The objective of the retrospective study was to describe growth and psychomotor development of patients with DMD and to detect a possible genotype-phenotype correlation. Data from 263 patients with DMD (mean age 7.1 years) treated at the Departments of Pediatric Neurology in three German University Hospitals was assessed with respect to body measurements (length, weight, body mass index BMI, head circumference OFC), motor and cognitive development as well as genotype (site of mutation). Anthropometric measures and developmental data were compared to those of a reference population and deviations were analyzed for their frequency in the cohort as well as in relation to the genotypes. Corticosteroid therapy was implemented in 29 from 263 patients. Overall 30% of the patients exhibit a short statue (length < 3rd centile) with onset early in development at 2-5 years of age, and this is even more prevalent when steroid therapy is applied (45% of patients with steroid therapy). The BMI shows a rightwards shift (68% > 50th centile) and the OFC a leftwards shift (65% < 50th centile, 5% microcephaly). Gross motor development is delayed in a third of the patients (mean age at walking 18.3 months, 30% > 18 months, 8% > 24 months). Almost half of the patients show cognitive impairment (26% learning disability, 17% intellectual disability). Although there is no strict genotype-phenotype correlation, particularly mutations in the distal part of the dystrophin gene are frequently associated with short stature and a high rate of microcephaly as well as cognitive impairment. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Perceived state of self during motion can differentially modulate numerical magnitude allocation.

PubMed

Arshad, Q; Nigmatullina, Y; Roberts, R E; Goga, U; Pikovsky, M; Khan, S; Lobo, R; Flury, A-S; Pettorossi, V E; Cohen-Kadosh, R; Malhotra, P A; Bronstein, A M

2016-09-01

Although a direct relationship between numerical allocation and spatial attention has been proposed, recent research suggests that these processes are not directly coupled. In keeping with this, spatial attention shifts induced either via visual or vestibular motion can modulate numerical allocation in some circumstances but not in others. In addition to shifting spatial attention, visual or vestibular motion paradigms also (i) elicit compensatory eye movements which themselves can influence numerical processing and (ii) alter the perceptual state of 'self', inducing changes in bodily self-consciousness impacting upon cognitive mechanisms. Thus, the precise mechanism by which motion modulates numerical allocation remains unknown. We sought to investigate the influence that different perceptual experiences of motion have upon numerical magnitude allocation while controlling for both eye movements and task-related effects. We first used optokinetic visual motion stimulation (OKS) to elicit the perceptual experience of either 'visual world' or 'self'-motion during which eye movements were identical. In a second experiment, we used a vestibular protocol examining the effects of perceived and subliminal angular rotations in darkness, which also provoked identical eye movements. We observed that during the perceptual experience of 'visual world' motion, rightward OKS-biased judgments towards smaller numbers, whereas leftward OKS-biased judgments towards larger numbers. During the perceptual experience of 'self-motion', judgments were biased towards larger numbers irrespective of the OKS direction. Contrastingly, vestibular motion perception was found not to modulate numerical magnitude allocation, nor was there any differential modulation when comparing 'perceived' vs. 'subliminal' rotations. We provide a novel demonstration that numerical magnitude allocation can be differentially modulated by the perceptual state of self during visual but not vestibular mediated motion. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

A rat model of unilateral hindpaw burn injury: slowly developing rightwards shift of the morphine dose-response curve.

PubMed

Wang, Shuxing; Lim, Grewo; Yang, Liling; Zeng, Qing; Sung, Backil; Jeevendra Martyn, J A; Mao, Jianren

2005-07-01

Management of pain after burn injury is an unresolved clinical issue. In a rat model of hindpaw burn injury, we examined the effects of systemic morphine on nociceptive behaviors following injury. Injury was induced by immersing the dorsal part of one hindpaw into a hot water bath (85 degrees C) for 4, 7, or 12 s under pentobarbital anesthesia. Mechanical allodynia to von Frey filament stimulation and thermal hyperalgesia to radiant heat were assessed. Burn injury induced by the 12-s (but not 4-, or 7-s) hot water immersion resulted in reliable and lasting mechanical allodynia and thermal hyperalgesia evident by day 1. In addition, there was an upregulation of protein kinase Cgamma and a progressive downregulation of mu-opioid receptors within the spinal cord dorsal horn ipsilateral to injury as revealed by immunohistochemistry and Western blot. In both injured and sham rats, the anti-nociceptive effects of subcutaneous morphine were examined on post-injury days 7 and 14. While the morphine AD50 dose was comparable on day 7 between burn (1.61 mg/kg) and control (1.7 mg/kg) rats, the morphine dose-response curve was shifted to the right in burn-injured rats (4.6 mg/kg) on post-injury day 14 as compared with both the injured rats on post-injury day 7 and sham rats on day 14 (1.72 mg/kg). These data indicate that hindpaw burn injury reliably produces persistent mechanical allodynia and thermal hyperalgesia and that the reduced efficacy of morphine anti-nociception in chronic burn injury may be in part due to a downregulation of spinal mu-opioid receptors.

Hemoglobin P(50) during a simulated ascent of Mt. Everest, Operation Everest II.

PubMed

Wagner, Peter D; Wagner, Harrieth E; Groves, Bertron M; Cymerman, Allen; Houston, Charles S

2007-01-01

The amount of O(2) available to tissues is essentially the product of cardiac output, [Hb], and O(2) saturation. Saturation depends on P(O2) and the O(2)Hb dissociation curve. With altitude, increased [2,3-DPG] shifts the dissociation curve rightward, but hypocapnia and alkalosis move it leftward. We determined both standard and in vivo P(50) in 5 fit subjects decompressed over 42 days in an altitude chamber to the equivalent of the Mt. Everest summit (Operation Everest II). Arterial and venous blood was sampled at five "altitudes " (P(B) = 760, 429, 347, 282, 253 mmHg), and P(O2), P(CO2), pH, O(2) saturation, [Hb] and [2,3-DPG] were measured. As reported previously, 2,3-DPG levels increased from 1.7 (P(B) = 760) to 3.8 mmol/L (P(B) = 282). Standard P(50) also increased (from 28.2 mmHg at sea level to 33.1 on the summit, p<0.001). Alone, this would have lowered saturation by 12 percentage points at a summit arterial P(O2) of approximately 30 mmHg. However, in vivo P(50) remained between 26 and 27 mmHg throughout due to progressive hypocapnia and alkalosis. Calculations suggest that the increase in standard P(50) did not affect summit V(O2 MAX)), alveolar, arterial and venous P(O2)'s, but reduced arterial and venous O(2) saturations by 8.4 and 17.4 points, respectively, and increased O(2) extraction by 7.9 percentage points. Reduced saturation was balanced by increased extraction, resulting in no significant overall O(2) transport benefit, thus leaving unanswered the question of the purpose of increased [2,3-DPG] concentrations at altitude.

Three-dimensional changes in left and right ventricular geometry in chronic mitral regurgitation.

PubMed

Young, A A; Orr, R; Smaill, B H; Dell'Italia, L J

1996-12-01

Regional three-dimensional (3-D) right (RV) and left ventricular (LV) geometry was studied in eight dogs before and 5-6 mo after induction of mitral regurgitation (MR). Ventricular shape changes were quantified with a 3-D finite-element model fitted to chamber contours traced on cardiac magnetic resonance images. MR increased LV end-diastolic volume (LVEDV; 99 vs. 57 ml; P < 0.001) and LV stroke volume (LVSV; 55 vs. 26 ml; P < 0.001). In contrast, RVEDV decreased (45 vs. 55 ml; P < 0.01), whereas SV was maintained. LV mass (free wall plus septum) increased (115 vs. 94 g; P < 0.05), whereas RV free-wall mass was relatively unchanged. Shape changes due to MR were characterized by a marked (7.4-mm) rightward shift of the septum relative to the lateral LV free wall at end diastole. In contrast, the distance from the RV free wall to the lateral LV free wall was relatively unchanged (2.7 mm). The distance between the LV lateral free wall and septum increased more than the distance between the anterior and posterior LV walls (22 vs. 15%; P = 0.04). During systole, the displacement of the septum into the LV increased significantly (7.3 vs. 2.9 mm; P < 0.01). Consistent with the end-diastolic dimension changes, LV endocardial circumferential curvature was decreased at end diastole to a greater extent in the anterior and posterior walls than in the septal and lateral walls (P < 0.01). Thus chronic MR produced an asymmetric LV dilatation with regional variation in geometry. The septum increased its contribution to the LVSV at the expense of RVEDV. RVSV was maintained, possibly by ventricular interaction.

Impaired Communication Between the Motor and Somatosensory Homunculus Is Associated With Poor Manual Dexterity in Autism Spectrum Disorder.

PubMed

Thompson, Abigail; Murphy, Declan; Dell'Acqua, Flavio; Ecker, Christine; McAlonan, Grainne; Howells, Henrietta; Baron-Cohen, Simon; Lai, Meng-Chuan; Lombardo, Michael V

2017-02-01

Fine motor skill impairments are common in autism spectrum disorder (ASD), significantly affecting quality of life. Sensory inputs reaching the primary motor cortex (M1) from the somatosensory cortex (S1) are likely involved in fine motor skill and specifically motor learning. However, the role of these connections has not been directly investigated in humans. This study aimed to investigate, for the first time, the role of the S1-M1 connections in healthy subjects in vivo and whether microstructural alterations are associated with motor impairment in ASD. Sixty right-handed neurotypical adult men aged 18 to 45 years, and 60 right-handed age- and sex-matched subjects diagnosed with ASD underwent fine motor skill assessment and scanning with diffusion tensor imaging (DTI). The streamlines of the hand region connecting S1-M1 of the motor-sensory homunculus were virtually dissected using TrackVis, and diffusion properties were extracted. The face/tongue region connections were used as control tracts. The ASD group displayed lower motor performances and altered DTI measurements of the hand-region connection. Behavioral performance correlated with hand-region DTI measures in both groups, but not with the face/tongue connections, indicating anatomical specificity. There was a left-hemisphere association of motor ability in the control group and an atypical rightward shift in the ASD group. These findings suggest that direct interaction between S1 and M1 may contribute to the human ability to precisely interact with and manipulate the environment. Because electrophysiological evidence indicates that these connections may underpin long-term potentiation in M1, our findings may lead to novel therapeutic treatments for motor skill disorders. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The leveling-off of oxygen uptake is related to blood lactate accumulation. Retrospective study of 94 elite rowers.

PubMed

Lacour, Jean-René; Messonnier, Laurent; Bourdin, Muriel

2007-09-01

To assess whether the ability to demonstrate a plateau in oxygen consumption VO2 could be related to adaptation to exercise, the data obtained over a period of 10 years on 94 elite oarsmen who had participated in annual testing were re-evaluated. The test consisted in an incremental step protocol until volitional exhaustion. VO2, heart rate (HR), blood lactate ([La]b) and respiratory exchange ratio (RER) were measured at each step. The maximal oxygen consumption (VO2max), the power corresponding to VO2maxPamax and the maximal power achieved (Ppeak) were recorded. Thirty-eight oarsmen achieved a VO2 plateau and were designated as Pla; 56 did not and were designed as N-Pla. The Pla and N-Pla VO2max, Pamax and maximal HR values were similar. In comparison with N-Pla, the Pla group displayed a rightward shift of the [La]b versus power curve, accounted for by both the increased percentage of VO2max corresponding to 4 mmol l(-1) and the decreased value of [La]b corresponding to Pamax (P<0.05). Pla oarsmen attained a higher Ppeak expressed as % of Pamax (P<0.05) and also showed better ergometer performance (P<0.05). In a sub-group of 53 oarsmen constituted on the basis of Pamax values close to 400 W, for a given power output, the Pla subjects had significantly lower HR, RER, and [La]b values at each sub-maximal stage of the test. These results suggest that achieving a [Formula: see text] plateau during completion of an incremental step protocol accounts for greater muscle ability to maintain homeostasis during exercise. These differences give the oarsmen an advantage in rowing competitions.

Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction

PubMed Central

Raasch, Walter; Schäfer, Ulrich; Qadri, Fatimunnisa; Dominiak, Peter

2002-01-01

Since agmatine has been identified as a clonidine displacing substance (CDS), the aim of this study was to investigate whether agmatine can mimic CDS-induced cardiovascular reactions in organ bath experiments, pithed spontaneously hypertensive rats (SHR) and anaesthetized SHR.Intravenously-administered agmatine significantly reduced the blood pressure and heart rate of anaesthetized SHR at doses higher than 1 and 3 mg kg−1, respectively. These effects are probably mediated via central mechanisms, since there was an approximate 8 fold rightward shift of the dose-response curve in the pithed SHR (indicating a weakened cardiovascular effect). Moreover, in organ bath experiments, agmatine failed to alter the contractility of intact or endothelium-denuded aortal rings. When agmatine was administered i.c.v. to anaesthetized SHR, blood pressure was increased without any alteration of heart rate, whereas blood pressure was unchanged and heart rate was increased after injection into the 4th brain ventricle. This suggests that haemodynamic reaction patterns after central application are related to distinct influences on central cardiovascular mechanisms.Agmatine reduces noradrenaline release in pithed SHR while α2-adrenoceptors are irreversibly blocked with phenoxybenzamine, but not while I1-binding sites are selectively blocked with AGN192403. This suggests that agmatine may modulate noradrenaline release in the same way that clonidine does, i.e. via imidazoline binding sites; this involves a reduction in sympathetic tone which in turn reduces blood pressure and heart rate.Finally, CDS-like cardiovascular activity appears not to be due to agmatine, since (i) blood pressure in anaesthetized SHR is decreased by agmatine and clonidine, and (ii) agmatine did not antagonize the blood pressure reaction to clonidine in pithed or anaesthetized SHR. PMID:11834614

Tachykinin-induced contraction of the guinea-pig isolated oesophageal mucosa is mediated by NK2 receptors

PubMed Central

Kerr, Karen P; Thai, Binh; Coupar, Ian M

2000-01-01

The tachykinin receptor present in the guinea-pig oesophageal mucosa that mediates contractile responses of the muscularis mucosae has been characterized, using functional in vitro experiments. The NK1 receptor-selective agonist, [Sar9(O2)Met11]SP and the NK3 receptor-selective agonists, [MePhe7]-NKB and senktide, produced no response at submicromolar concentrations. The NK2 receptor-selective agonists, [Nle10]-NKA(4–10), and GR 64,349 produced concentration-dependent contractile effects with pD2 values of 8.20±0.16 and 8.30±0.15, respectively. The concentration-response curve to the non-selective agonist, NKA (pD2=8.13±0.04) was shifted significantly rightwards only by the NK2 receptor-selective antagonist, GR 159,897 and was unaffected by the NK1 receptor-selective antagonist, SR 140,333 and the NK3 receptor-selective antagonist, SB 222,200. The NK2 receptor-selective antagonist, GR 159,897, exhibited an apparent competitive antagonism against the NK2 receptor-selective agonist, GR 64,349 (apparent pKB value=9.29±0.16) and against the non-selective agonist, NKA (apparent pKB value=8.71±0.19). The NK2 receptor-selective antagonist, SR 48,968 exhibited a non-competitive antagonism against the NK2 receptor-selective agonist, [Nle10]-NKA(4–10). The pKB value was 10.84±0.19. It is concluded that the guinea-pig isolated oesophageal mucosa is a useful preparation for studying the effects of NK2 receptor-selective agonists and antagonists as the contractile responses to various tachykinins are mediated solely by NK2 receptors. PMID:11090121

Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

PubMed

Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

2018-06-01

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

PubMed

Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

Further investigation into the signal transduction mechanism of the 5-HT4-like receptor in the circular smooth muscle of human colon.

PubMed Central

McLean, P. G.; Coupar, I. M.

1996-01-01

1. The nature of the receptor coupling mechanism of the 5-hydroxytryptamine4 (5-HT4) receptor in the circular smooth muscle of the human colon has been further investigated. 2. 5-HT stimulated cyclic AMP generation and caused a relaxation in a concentration-dependent fashion, with EC50 values of 175.5 and 274.9 nM respectively. DAU 6236 increased cyclic AMP formation and caused a relaxant effect but was a partial agonist relative to 5-HT. 3. The 5-HT4 receptor antagonist, GR 113808, inhibited cyclic AMP formation and relaxation induced by 5-HT with -log Ki values of 9.1 (cyclic AMP) and 8.9 (relaxation) and apparent pA2 values of 9.2 (cyclic AMP) and 9.5 (relaxation). 4. Ondansetron and methysergide failed to inhibit cyclic AMP formation or the relaxation induced by 5-HT. 5. The phosphodiesterase inhibitor, IBMX, produced a concentration-dependent relaxation (EC50 = 30 microM) and at 1 microM it enhanced the 5-HT-induced relaxation producing a leftward shift of the 5-HT concentration-effect curve with a concentration-ratio of 4.1. Rolipram caused a concentration-dependent relaxation (EC50 = 564.8 nM) and at 200 nm caused a leftward shift of the concentration-effect curve to 5-HT with a concentration-ratio of 5.5. 6. Application of the adenylyl cyclase inhibitor, SQ 22536 (0.1 mM), and the protein kinase inhibitors, H7 (100 nM) and H89 (200 nM), inhibited the relaxant effect of 5-HT inducing a rightward shift of the concentration-effect curve with concentration-ratios of 10.1, 2.7 and 4.2 respectively. 7. Forskolin stimulated cyclic AMP production and caused a relaxation. The maximum relaxant effect of forskolin (6 microM, 13.8 +/- 1.9 cm.s) was not significantly different from the maximum relaxant effect of 5-HT (10 microM, 12.7 +/- 4.9 cm.s). However, the cyclic AMP levels stimulated by forskolin (6 microM, 49.3 +/- 6.6 pmol mg-1) were markedly greater than those stimulated by 5-HT (10 microM, 7.6 +/- 2.0 pmol mg-1). 8. In conclusion, these results indicate that the 5-HT4 receptors of the circular smooth muscle of human colon mediate relaxation and inhibition of spontaneous contractions via activation of adenylyl cyclase, formation of cyclic AMP and activation of protein kinase A. PMID:8799582

Further investigation into the signal transduction mechanism of the 5-HT4-like receptor in the circular smooth muscle of human colon.

PubMed

McLean, P G; Coupar, I M

1996-06-01

1. The nature of the receptor coupling mechanism of the 5-hydroxytryptamine4 (5-HT4) receptor in the circular smooth muscle of the human colon has been further investigated. 2. 5-HT stimulated cyclic AMP generation and caused a relaxation in a concentration-dependent fashion, with EC50 values of 175.5 and 274.9 nM respectively. DAU 6236 increased cyclic AMP formation and caused a relaxant effect but was a partial agonist relative to 5-HT. 3. The 5-HT4 receptor antagonist, GR 113808, inhibited cyclic AMP formation and relaxation induced by 5-HT with -log Ki values of 9.1 (cyclic AMP) and 8.9 (relaxation) and apparent pA2 values of 9.2 (cyclic AMP) and 9.5 (relaxation). 4. Ondansetron and methysergide failed to inhibit cyclic AMP formation or the relaxation induced by 5-HT. 5. The phosphodiesterase inhibitor, IBMX, produced a concentration-dependent relaxation (EC50 = 30 microM) and at 1 microM it enhanced the 5-HT-induced relaxation producing a leftward shift of the 5-HT concentration-effect curve with a concentration-ratio of 4.1. Rolipram caused a concentration-dependent relaxation (EC50 = 564.8 nM) and at 200 nm caused a leftward shift of the concentration-effect curve to 5-HT with a concentration-ratio of 5.5. 6. Application of the adenylyl cyclase inhibitor, SQ 22536 (0.1 mM), and the protein kinase inhibitors, H7 (100 nM) and H89 (200 nM), inhibited the relaxant effect of 5-HT inducing a rightward shift of the concentration-effect curve with concentration-ratios of 10.1, 2.7 and 4.2 respectively. 7. Forskolin stimulated cyclic AMP production and caused a relaxation. The maximum relaxant effect of forskolin (6 microM, 13.8 +/- 1.9 cm.s) was not significantly different from the maximum relaxant effect of 5-HT (10 microM, 12.7 +/- 4.9 cm.s). However, the cyclic AMP levels stimulated by forskolin (6 microM, 49.3 +/- 6.6 pmol mg-1) were markedly greater than those stimulated by 5-HT (10 microM, 7.6 +/- 2.0 pmol mg-1). 8. In conclusion, these results indicate that the 5-HT4 receptors of the circular smooth muscle of human colon mediate relaxation and inhibition of spontaneous contractions via activation of adenylyl cyclase, formation of cyclic AMP and activation of protein kinase A.

Hypotensive effect of aqueous extract of Averrhoa carambola L. (Oxalidaceae) in rats: an in vivo and in vitro approach.

PubMed

Soncini, Roseli; Santiago, Michael B; Orlandi, Lidiane; Moraes, Gabriel O I; Peloso, André Luiz M; dos Santos, Marcelo H; Alves-da-Silva, Geraldo; Paffaro, Valdemar A; Bento, Antonio C; Giusti-Paiva, Alexandre

2011-01-27

Averrhoa carambola L. (Oxalidaceae) leaves are used in Brazilian traditional medicine to treat hypertension. This study was conducted to evaluate the hypotensive effect of the aqueous extract of Averrhoa carambola (AEAc) and its underlying mechanisms in the isolated rat aorta. The effect of AEAc on the mean arterial pressure (MAP) was determined in vivo in anesthetized rats. In vitro, thoracic aortic rings were isolated and suspended in organ baths, and the effects of AEAc were studied by means of isometric tension recording experiments. In HPLC analysis, the fingerprint chromatogram of AEAc was established. In normotensive rats, AEAc (12.5-50.0 mg/kg, i.v.) induced dose-dependent hypotension. In vitro, AEAc caused a depression in the E(max) response to phenylephrine without a change in sensibility. Also, in a depolarized Ca(2+)-free medium, AEAc inhibited CaCl(2)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that AEAc inhibited the contractile mechanisms involving extracellular Ca(2+) influx. These results demonstrate the hypotensive effects of AEAc, and these effects may, in part, be due to the inhibition of Ca(2+), which supports previous claims of its traditional use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of Acute and Chronic Flunitrazepam on Delay Discounting in Pigeons

PubMed Central

Eppolito, Amy K; France, Charles P; Gerak, Lisa R

2011-01-01

Delay to delivery of a reinforcer can decrease responding for that reinforcer and increase responding for smaller reinforcers that are available concurrently and delivered without delay; acute administration of drugs can alter responding for large, delayed reinforcers, although the impact of chronic treatment on delay discounting is not well understood. In this experiment, the effects of repeated administration of the benzodiazepine flunitrazepam were studied in 6 pigeons responding on one key to receive food that was delivered immediately and on a second key to receive a larger amount of food that was delivered following delays which increased across a single session. Pigeons responded predominantly for the large reinforcer when there were no delays and when delays were short; however, as delays increased, responding for the large reinforcer decreased. Acutely, flunitrazepam (0.32, 1.0 and 3.2 mg/kg) dose-dependently increased responding for the large reinforcer, shifting the discounting curve rightward and upward. Repeated administration of flunitrazepam (0.32, 1.0 and 3.2 mg/kg, each for six sessions, separated by one session during which vehicle was administered) did not markedly alter its effects on responding for the large reinforcer, indicating that the development of tolerance to this effect of flunitrazepam is modest under these conditions. PMID:21541119

The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study

PubMed Central

Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D.

2011-01-01

In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured by anatomical magnetic resonance imaging. The relationships of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages four to seventeen). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volumes of right thalami are significantly larger than that of left in both genders with greater rightward asymmetry and greater thalamus/grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volumes. Larger thalami were associated with higher verbal IQ. This normative pediatric data is of value to researchers who study these regions in neurodevelopmental disorders. PMID:21954432

The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study.

PubMed

Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D

2012-03-01

In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured anatomically magnetic resonance imaging. The relations of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages 4 to 17). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volume of the right thalamus is significantly larger than that of the left in both genders, with greater rightward asymmetry and greater thalamus to grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volume. Larger thalami were associated with higher Verbal IQ. These normative pediatric data are of value to researchers who study these regions in neurodevelopmental disorders.

Perceptual Span Depends on Font Size during the Reading of Chinese Sentences

ERIC Educational Resources Information Center

Yan, Ming; Zhou, Wei; Shu, Hua; Kliegl, Reinhold

2015-01-01

The present study explored the perceptual span (i.e., the physical extent of an area from which useful visual information is extracted during a single fixation) during the reading of Chinese sentences in 2 experiments. In Experiment 1, we tested whether the rightward span can go beyond 3 characters when visually similar masks were used. Results…

BamHI-A rightward frame 1, an Epstein–Barr virus-encoded oncogene and immune modulator

PubMed Central

Hoebe, Eveline K; Le Large, Tessa Y S; Greijer, Astrid E; Middeldorp, Jaap M

2013-01-01

Epstein–Barr virus (EBV) causes several benign and malignant disorders of lymphoid and epithelial origin. EBV-related tumors display distinct patterns of viral latent gene expression, of which the BamHI-A rightward frame 1 (BARF1) is selectively expressed in carcinomas, regulated by cellular differentiation factors including ΔNp63α. BARF1 functions as a viral oncogene, immortalizing and transforming epithelial cells of different origin by acting as a mitogenic growth factor, inducing cyclin-D expression, and up-regulating antiapoptotic Bcl-2, stimulating host cell growth and survival. In addition, secreted hexameric BARF1 has immune evasive properties, functionally corrupting macrophage colony stimulating factor, as supported by recent functional and structural data. Therefore, BARF1, an intracellular and secreted protein, not only has multiple pathogenic functions but also can function as a target for immune responses. Deciphering the role of BARF1 in EBV biology will contribute to novel diagnostic and treatment options for EBV-driven carcinomas. Herein, we discuss recent insights on the regulation of BARF1 expression and aspects of structure-function relating to its oncogenic and immune suppressive properties. © 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd. PMID:23996634

Vestibular stimulation, spatial hemineglect and dysphasia, selective effects.

PubMed

Vallar, G; Papagno, C; Rusconi, M L; Bisiach, E

1995-09-01

The selectivity of the effects of vestibular stimulation was investigated in a left brain-damaged patient suffering from right visuo-spatial hemineglect and severe dysplasia. Vestibular stimulation temporarily improved the former but not the latter disorder. These results support the view that this treatment improves hemineglect by a specific effect, running counter the rightward distortion of egocentric co-ordinates, rather than by a general hemispheric activation.

Stimulant Treatment Reduces Lapses in Attention among Children with ADHD: The Effects of Methylphenidate on Intra-Individual Response Time Distributions

ERIC Educational Resources Information Center

Spencer, Sarah V.; Hawk, Larry W., Jr.; Richards, Jerry B.; Shiels, Keri; Pelham, William E., Jr.; Waxmonsky, James G.

2009-01-01

Recent research has suggested that intra-individual variability in reaction time (RT) distributions of children with ADHD is characterized by a particularly large rightward skew that may reflect lapses in attention. The purpose of the study was to provide the first randomized, placebo-controlled test of the effects of the stimulant methylphenidate…

Image of a line is not shrunk but neglected. Absence of crossover in unilateral spatial neglect.

PubMed

Ishiai, Sumio; Koyama, Yasumasa; Nakano, Naomi; Seki, Keiko; Nishida, Yoichiro; Hayashi, Kazuko

2004-01-01

Patients with left unilateral spatial neglect following right hemisphere lesions usually err rightward when bisecting a horizontal line. For very short lines (e.g. 25 mm), however, leftward errors or seemingly 'right' neglect is often observed. To explain this paradox of crossover in the direction of errors, rather complicated models have been introduced as to the distribution of attention. Neglect may be hypothesized to occur in representational process of a line or estimation of the midpoint on the formed image, or both. We devised a line image task using a computer display with a touch panel and approached the representational image of a line to be bisected. Three patients with typical left neglect were presented with a line and forced to see its whole extent with cueing to the left endpoint. After disappearance of the line, they pointed to the right endpoint, the left endpoint, or the subjective midpoint according to their representational image. The line image between the reproduced right and left endpoints was appropriately formed for the 200 mm lines. However, the images for the shorter 25 and 100 mm lines were longer than the physical lengths with overextension to the left side. These results proved the context effect that short lines may be perceived longer when they are presented in combination with longer lines. One of our patients had an extensive lesion that involved the frontal, temporal, and parietal lobes, and the other two had a lesion restricted to the posterior right hemisphere. The image for a fully perceived line may be represented far enough into left space even when left neglect occurs after a lesion that involves the right parietal lobe. The patients with neglect placed the subjective midpoint rightward from the centre of the stimulus line for the 100 and 200 mm lines and leftward for the 25 mm lines. This crossover of bisection errors disappeared when the displacement of the subjective midpoint was measured from the centre of the representational line image. Left neglect may occur consistently in estimation of the subjective midpoint on the representational image, which may be explained by a simple rightward bias of attentional distribution.

Pharmacological characterization of the 5-HT receptor-mediated contraction in the mouse isolated ileum

PubMed Central

Tuladhar, B R; Womack, M D; Naylor, R J

2000-01-01

The pharmacological characterization of a 5-HT receptor-mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 μM), 5-hydroxytryptamine (5-HT, 0.3–100 μM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC50 value of 5.47±0.09. The 5-HT3 receptor selective agonists m-chlorophenylbiguanide (0.3–100 μM, pEC50 5.81±0.04), 1-phenylbiguanide (3–100 μM, pEC50 5.05±0.06) and 2-methyl-5-HT (3–100 μM, pEC50 5.00±0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1–100 μM), RS 67506 (0.1–100 μM) and α-methyl-5-HT (0.1–100 μM) failed to mimic the 5-HT responses. The contractile response to 5-HT was not antagonized by either 5-HT2 receptor antagonists ritanserin (0.1 μM) or ketanserin (1 μM) nor the 5-HT4 receptor antagonist SB 204070 (0.1 μM). The 5-HT3 receptor selective antagonists granisetron (0.3–1 nM), tropisetron (1–10 nM), ondansetron (10 nM–1 μM) and MDL 72222 (10 nM–1 μM) caused rightward displacement of the concentration-response curves to 5-HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration-response curves to 5-HT with apparent pKB values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5-HT was abolished by tetrodotoxin (0.3 μM); atropine (0.1 and 1 μM) decreased the maximum response of the 5-HT concentration-response curve by approximately 65%. It is concluded that a neuronally located 5-HT3 receptor mediates a contractile response to 5-HT in the mouse ileum. The 5-HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea-pig ileum. PMID:11139451

Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.

PubMed

Hillman, Kristin L; Doze, Van A; Porter, James E

2005-08-01

Recent studies have demonstrated that activation of the beta-adrenergic receptor (AR) using the selective beta-AR agonist isoproterenol (ISO) facilitates pyramidal cell long-term potentiation in the cornu ammonis 1 (CA1) region of the rat hippocampus. We have previously analyzed beta-AR genomic expression patterns of 17 CA1 pyramidal cells using single cell reverse transcription-polymerase chain reaction, demonstrating that all samples expressed the beta2-AR transcript, with four of the 17 cells additionally expressing mRNA for the beta1-AR subtype. However, it has not been determined which beta-AR subtypes are functionally expressed in CA1 for these same pyramidal neurons. Using cell-attached recordings, we tested the ability of ISO to increase pyramidal cell action potential (AP) frequency in the presence of subtype-selective beta-AR antagonists. ICI-118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] and butoxamine [alpha-[1-(t-butylamino)ethyl]-2,5-dimethoxybenzyl alcohol) hydrochloride], agents that selectively block the beta2-AR, produced significant parallel rightward shifts in the concentration-response curves for ISO. From these curves, apparent equilibrium dissociation constant (K(b)) values of 0.3 nM for ICI-118,551 and 355 nM for butoxamine were calculated using Schild regression analysis. Conversely, effective concentrations of the selective beta1-AR antagonists CGP 20712A [(+/-)-2-hydroxy-5-[2-([2-hydroxy-3-(4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy)propyl]amino)ethoxy]-benzamide methanesulfonate] and atenolol [4-[2'-hydroxy-3'-(isopropyl-amino)propoxy]phenylacetamide] did not significantly affect the pyramidal cell response to ISO. However, at higher concentrations, atenolol significantly decreased the potency for ISO-mediated AP frequencies. From these curves, an apparent atenolol K(b) value of 3162 nM was calculated. This pharmacological profile for subtype-selective beta-AR antagonists indicates that beta2-AR activation is mediating the increased AP frequency. Knowledge of functional AR expression in CA1 pyramidal neurons will aid future long-term potentiation studies by allowing selective manipulation of specific beta-AR subtypes.

Mechanism-based model for tumor drug resistance.

PubMed

Kuczek, T; Chan, T C

1992-01-01

The development of tumor resistance to cytotoxic agents has important implications in the treatment of cancer. If supported by experimental data, mathematical models of resistance can provide useful information on the underlying mechanisms and aid in the design of therapeutic regimens. We report on the development of a model of tumor-growth kinetics based on the assumption that the rates of cell growth in a tumor are normally distributed. We further assumed that the growth rate of each cell is proportional to its rate of total pyrimidine synthesis (de novo plus salvage). Using an ovarian carcinoma cell line (2008) and resistant variants selected for chronic exposure to a pyrimidine antimetabolite, N-phosphonacetyl-L-aspartate (PALA), we derived a simple and specific analytical form describing the growth curves generated in 72 h growth assays. The model assumes that the rate of de novo pyrimidine synthesis, denoted alpha, is shifted down by an amount proportional to the log10 PALA concentration and that cells whose rate of pyrimidine synthesis falls below a critical level, denoted alpha 0, can no longer grow. This is described by the equation: Probability (growth) = probability (alpha 0 less than alpha-constant x log10 [PALA]). This model predicts that when growth curves are plotted on probit paper, they will produce straight lines. This prediction is in agreement with the data we obtained for the 2008 cells. Another prediction of this model is that the same probit plots for the resistant variants should shift to the right in a parallel fashion. Probit plots of the dose-response data obtained for each resistant 2008 line following chronic exposure to PALA again confirmed this prediction. Correlation of the rightward shift of dose responses to uridine transport (r = 0.99) also suggests that salvage metabolism plays a key role in tumor-cell resistance to PALA. Furthermore, the slope of the regression lines enables the detection of synergy such as that observed between dipyridamole and PALA. Although the rate-normal model was used to study the rate of salvage metabolism in PALA resistance in the present study, it may be widely applicable to modeling of other resistance mechanisms such as gene amplification of target enzymes.

Intra-hemispheric intrinsic connectivity asymmetry and its relationships with handedness and language Lateralization.

PubMed

Joliot, M; Tzourio-Mazoyer, N; Mazoyer, B

2016-12-01

Asymmetry in intra-hemispheric intrinsic connectivity, and its association with handedness and hemispheric dominance for language, were investigated in a sample of 290 healthy volunteers enriched in left-handers (52.7%). From the resting-state FMRI data of each participant, we derived an intra-hemispheric intrinsic connectivity asymmetry (HICA) matrix as the difference between the left and right intra-hemispheric matrices of intrinsic correlation computed for each pair of the AICHA atlas ROIs. We defined a similarity measure between the HICA matrices of two individuals as the correlation coefficient of their corresponding elements, and computed for each individual an index of intra-hemispheric intrinsic connectivity asymmetry as the average similarity measure of his HICA matrix to those of the other subjects of the sample (HICAs). Gaussian-mixture modeling of the age-corrected HICAs sample distribution revealed that two types of HICA patterns were present, one (Typical_HICA) including 92.4% of the participants while the other (Atypical_HICA) included only 7.6% of them, mostly left-handers. In addition, we investigated the relationship between asymmetry in intra-hemispheric intrinsic connectivity and language hemispheric dominance, including a potential effect of handedness on this relationship, thanks to an FMRI acquisition during language production from which an hemispheric functional lateralization index for language (HFLI) and a type of hemispheric dominance for language, namely leftward, ambilateral, or rightward, were derived for each individual. There was a significant association between the types of language hemispheric dominance and of intra-hemispheric intrinsic connectivity asymmetry, occurrence of Atypical_HICAs individuals being very high in the group of individuals rightward-lateralized for language (80%), reduced in the ambilateral group (19%) and rare in individuals leftward-lateralized for language (less than 3%). Quantitatively, we found a significant positive linear relationship between the HICAs and HFLI indices, with an effect of handedness on the intercept but not on the slope of this relationship. These findings demonstrate that handedness and hemispheric dominance for language are significantly but independently associated with the asymmetry of intra-hemispheric intrinsic connectivity. These findings suggest that asymmetry in intra-hemispheric connectivity is a variable phenotype shaped in part by hemispheric lateralization for language, but possibly also depending on other lateralized functions. Copyright © 2016 Elsevier Ltd. All rights reserved.

How the embryonic chick brain twists.

PubMed

Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A

2016-11-01

During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain. © 2016 The Author(s).

Stimulus-response incompatibility activates cortex proximate to three eye fields

NASA Technical Reports Server (NTRS)

Merriam, E. P.; Colby, C. L.; Thulborn, K. R.; Luna, B.; Olson, C. R.; Sweeney, J. A.

2001-01-01

We used functional magnetic resonance imaging (fMRI) to investigate cortical activation during the performance of three oculomotor tasks that impose increasing levels of cognitive demand. (1) In a visually guided saccade (VGS) task, subjects made saccades to flashed targets. (2) In a compatible task, subjects made leftward and rightward saccades in response to foveal presentation of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made rightward saccades in response to the lowercase word "left" and leftward saccades in response to the lowercase word "right" on incompatible trials (60%). The remaining 40% of trials required compatible responses to uppercase words. The VGS and compatible tasks, when compared to fixation, activated the three cortical eye fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the parietal eye field (PEF). The mixed task, when compared to the compatible task, activated three additional cortical regions proximate to the three eye fields: (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in posterior parietal cortex. These areas may contribute to the suppression of prepotent responses and in holding novel visuomotor associations in working memory. Copyright 2001 Academic Press.

Alterations of grey matter asymmetries in adolescents with prelingual deafness: a combined VBM and cortical thickness analysis.

PubMed

Li, Wenjing; Li, Jianhong; Xian, Junfang; Lv, Bin; Li, Meng; Wang, Chunheng; Li, Yong; Liu, Zhaohui; Liu, Sha; Wang, Zhenchang; He, Huiguang; Sabel, Bernhard A

2013-01-01

Prelingual deafness has been shown to lead to brain reorganization as demonstrated by functional parameters, but anatomical evidences still remain controversial. The present study investigated hemispheric asymmetry changes in deaf subjects using MRI, hypothesizing auditory-, language- or visual-related regions after early deafness. Prelingually deaf adolescents (n = 16) and age- and gender-matched normal controls (n = 16) were recruited and hemispheric asymmetry was evaluated with voxel-based morphometry (VBM) from MRI combined with analysis of cortical thickness (CTh). Deaf adolescents showed more rightward asymmetries (L < R) of grey matter volume (GMV) in the cerebellum and more leftward CTh asymmetries (L > R) in the posterior cingulate gyrus and gyrus rectus. More rightward CTh asymmetries were observed in the precuneus, middle and superior frontal gyri, and middle occipital gyrus. The duration of hearing aid use was correlated with asymmetry of GMV in the cerebellum and CTh in the gyrus rectus. Interestingly, the asymmetry of the auditory cortex was preserved in deaf subjects. When the brain is deprived of auditory input early in life there are signs of both irreversible morphological asymmetry changes in different brain regions but also signs of reorganization and plasticity which are dependent on hearing aid use, i.e. use-dependent.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis

PubMed Central

Premkumar, Preethi; Fannon, Dominic; Sapara, Adegboyega; Peters, Emmanuelle R.; Anilkumar, Anantha P.; Simmons, Andrew; Kuipers, Elizabeth; Kumari, Veena

2015-01-01

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6–8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness. PMID:25659473

Seeing Your Error Alters My Pointing: Observing Systematic Pointing Errors Induces Sensori-Motor After-Effects

PubMed Central

Ronchi, Roberta; Revol, Patrice; Katayama, Masahiro; Rossetti, Yves; Farnè, Alessandro

2011-01-01

During the procedure of prism adaptation, subjects execute pointing movements to visual targets under a lateral optical displacement: As consequence of the discrepancy between visual and proprioceptive inputs, their visuo-motor activity is characterized by pointing errors. The perception of such final errors triggers error-correction processes that eventually result into sensori-motor compensation, opposite to the prismatic displacement (i.e., after-effects). Here we tested whether the mere observation of erroneous pointing movements, similar to those executed during prism adaptation, is sufficient to produce adaptation-like after-effects. Neurotypical participants observed, from a first-person perspective, the examiner's arm making incorrect pointing movements that systematically overshot visual targets location to the right, thus simulating a rightward optical deviation. Three classical after-effect measures (proprioceptive, visual and visual-proprioceptive shift) were recorded before and after first-person's perspective observation of pointing errors. Results showed that mere visual exposure to an arm that systematically points on the right-side of a target (i.e., without error correction) produces a leftward after-effect, which mostly affects the observer's proprioceptive estimation of her body midline. In addition, being exposed to such a constant visual error induced in the observer the illusion “to feel” the seen movement. These findings indicate that it is possible to elicit sensori-motor after-effects by mere observation of movement errors. PMID:21731649

Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

NASA Astrophysics Data System (ADS)

Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

2006-03-01

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

Stretch-activated ion channel blockade attenuates adaptations to eccentric exercise.

PubMed

Butterfield, Timothy A; Best, Thomas M

2009-02-01

The purpose of this study was to test the hypothesis that stretch-activated ion channel (SAC) function is essential for the repeated bout effect (RBE) in skeletal muscle. Specifically, we investigated if daily injections of streptomycin (a known SAC blocker) would abrogate the muscle's adaptive resistance to the damaging effects of eccentric exercise over a 4-wk period. Furthermore, we hypothesized that the lack of an RBE would be due to the lack of functional adaptations that typically result from repeated bouts of eccentric exercise, including increased peak isometric torque, muscle hypertrophy, and rightward shift of the torque-angle relationship. Twelve New Zealand white rabbits were each subjected to 12 bouts of eccentric exercise over a 4-wk period while receiving either daily injections of streptomycin or sham injections. Although blocking the SAC function completely eliminated the expected adaptive response in biomechanical parameters during the exercise regimen, there remained evidence of an acquired RBE, albeit with an attenuated response when compared with the muscles with intact SAC function. Blocking sarcolemmal SAC eliminates functional adaptations of muscle after eccentric exercise. In the absence of SAC function, muscles subjected to chronic eccentric exercise still exhibit some degree of the RBE. As such, it appears that the signaling cascade that results in functional, biomechanical adaptations associated with the RBE during eccentric exercise is dependent upon intact SAC function.

The impact of musicianship on the cortical mechanisms related to separating speech from background noise.

PubMed

Zendel, Benjamin Rich; Tremblay, Charles-David; Belleville, Sylvie; Peretz, Isabelle

2015-05-01

Musicians have enhanced auditory processing abilities. In some studies, these abilities are paralleled by an improved understanding of speech in noisy environments, partially due to more robust encoding of speech signals in noise at the level of the brainstem. Little is known about the impact of musicianship on attention-dependent cortical activity related to lexical access during a speech-in-noise task. To address this issue, we presented musicians and nonmusicians with single words mixed with three levels of background noise, across two conditions, while monitoring electrical brain activity. In the active condition, listeners repeated the words aloud, and in the passive condition, they ignored the words and watched a silent film. When background noise was most intense, musicians repeated more words correctly compared with nonmusicians. Auditory evoked responses were attenuated and delayed with the addition of background noise. In musicians, P1 amplitude was marginally enhanced during active listening and was related to task performance in the most difficult listening condition. By comparing ERPs from the active and passive conditions, we isolated an N400 related to lexical access. The amplitude of the N400 was not influenced by the level of background noise in musicians, whereas N400 amplitude increased with the level of background noise in nonmusicians. In nonmusicians, the increase in N400 amplitude was related to a reduction in task performance. In musicians only, there was a rightward shift of the sources contributing to the N400 as the level of background noise increased. This pattern of results supports the hypothesis that encoding of speech in noise is more robust in musicians and suggests that this facilitates lexical access. Moreover, the shift in sources suggests that musicians, to a greater extent than nonmusicians, may increasingly rely on acoustic cues to understand speech in noise.

Contrast of hemispheric lateralization for oro-facial movements between learned attention-getting sounds and species-typical vocalizations in chimpanzees: Extension in a second colony

PubMed Central

Wallez, Catherine; Schaeffer, Jennifer; Meguerditchian, Adrien; Vauclair, Jacques; Schapiro, Steven J.; Hopkins, William D.

2013-01-01

Studies involving oro-facial asymmetries in nonhuman primates have largely demonstrated a right hemispheric dominance for communicative signals and conveyance of emotional information. A recent study on chimpanzee reported the first evidence of significant left-hemispheric dominance when using attention-getting sounds and rightward bias for species-typical vocalizations (Losin, Russell, Freeman, Meguerditchian, Hopkins & Fitch, 2008). The current study sought to extend the findings from Losin et al. (2008) with additional oro-facial assessment in a new colony of chimpanzees. When combining the two populations, the results indicated a consistent leftward bias for attention-getting sounds and a right lateralization for species-typical vocalizations. Collectively, the results suggest that both voluntary- controlled oro-facial and gestural communication might share the same left-hemispheric specialization and might have coevolved into a single integrated system present in a common hominid ancestor. PMID:22867751

Identification of the fatty acid activation site on human ClC-2.

PubMed

Cuppoletti, John; Tewari, Kirti P; Chakrabarti, Jayati; Malinowska, Danuta H

2017-06-01

Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl - channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a four-amino acid PKA activation site, RGET 691 , of hClC-2 was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP concentration ([cAMP] i ), EP 2 , or EP 4 receptor agonist activity. All fatty acids [lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and elaidic acid] caused significant rightward shifts in concentration-dependent Cl - current activation (increasing EC 50 s) with mutant compared with WT hClC-2 channels, without changing time and voltage dependence, current-voltage rectification, or methadone inhibition of the channel. As with lubiprostone, cobiprostone activation of hClC-2 occurred with PKA inhibitor (myristoylated protein kinase inhibitor) present or when using double PKA activation site (RRAA 655 /RGEA 691 ) mutant. Cobiprostone did not activate human CFTR. Fatty acids did not increase [cAMP] i in hClC-2/293EBNA or T84 cells. Using T84 CFTR knockdown cells, cobiprostone increased hClC-2 Cl - currents without increasing [cAMP] i, while PGE 2 and forskolin-IBMX increased both. Fatty acids were not agonists of EP 2 or EP 4 receptors. L-161,982, a supposed EP 4 -selective inhibitor, had no effect on lubiprostone-activated hClC-2 Cl - currents but significantly decreased T84 cell barrier function measured by transepithelial resistance and fluorescent dextran transepithelial movement. The present findings show that RGET 691 of hClC-2 (possible binding site) plays an important functional role in fatty acid activation of hClC-2. PKA, [cAMP] i , and EP 2 or EP 4 receptors are not involved. These studies provide the molecular basis for fatty acid regulation of hClC-2. Copyright © 2017 the American Physiological Society.

Hemispheric asymmetry: Looking for a novel signature of the modulation of spatial attention in multisensory processing.

PubMed

Chen, Yi-Chuan; Spence, Charles

2017-06-01

The extent to which attention modulates multisensory processing in a top-down fashion is still a subject of debate among researchers. Typically, cognitive psychologists interested in this question have manipulated the participants' attention in terms of single/dual tasking or focal/divided attention between sensory modalities. We suggest an alternative approach, one that builds on the extensive older literature highlighting hemispheric asymmetries in the distribution of spatial attention. Specifically, spatial attention in vision, audition, and touch is typically biased preferentially toward the right hemispace, especially under conditions of high perceptual load. We review the evidence demonstrating such an attentional bias toward the right in extinction patients and healthy adults, along with the evidence of such rightward-biased attention in multisensory experimental settings. We then evaluate those studies that have demonstrated either a more pronounced multisensory effect in right than in left hemispace, or else similar effects in the two hemispaces. The results suggest that the influence of rightward-biased attention is more likely to be observed when the crossmodal signals interact at later stages of information processing and under conditions of higher perceptual load-that is, conditions under which attention is perhaps a compulsory enhancer of information processing. We therefore suggest that the spatial asymmetry in attention may provide a useful signature of top-down attentional modulation in multisensory processing.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis.

PubMed

Premkumar, Preethi; Fannon, Dominic; Sapara, Adegboyega; Peters, Emmanuelle R; Anilkumar, Anantha P; Simmons, Andrew; Kuipers, Elizabeth; Kumari, Veena

2015-03-30

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Cerebral volumetric asymmetries in non-human primates: A magnetic resonance imaging study

PubMed Central

Pilcher, Dawn L.; Hammock, Elizabeth A.D.; Hopkins, William D.

2007-01-01

Magnetic resonance images (MRI) were collected in a sample of 23 apes, 14 Old World monkeys, and 8 New World monkeys. The total area or volume of the anterior and posterior cerebral regions of each hemisphere of the brain was measured. The results indicated that a rightward frontal and leftward occipital pattern of asymmetry was present at a population level in the great ape sample. Population-level cerebral asymmetries were not revealed in the sample of New or Old World monkeys. The total area or volume of the planum temporale, which was localised only in the great apes, was also measured in both hemispheres. A leftward planum temporale asymmetry was evident at the population level in the great apes. It was hypothesised that the rightward frontal and leftward occipital asymmetries would correlate with leftward planum temporale asymmetries. This hypothesis was based on the assumption that, similar to development of the human brain, the non-human primate brain ‘‘torques’’ during development due to a growth gradient which progresses anterior to posterior, ventral to dorsal, and right to left. The results of this study confirmed the predicted relationship between cerebral volume and the planum temporale asymmetries. This supports the hypothesis that the great ape brain may develop in a ‘‘torquing’’ manner, producing similar anatomical asymmetries as reported in humans. PMID:15513168

Sylvian Fissure Asymmetries in Nonhuman Primates Revisited: A Comparative MRI Study

PubMed Central

Hopkins, William D.; Pilcher, Dawn L.; MacGregor, Leslie

2007-01-01

Magnetic resonance images (MRI) were collected in a sample of 28 apes, 16 Old World monkeys and 8 New World monkeys. The length of the sylvian fissure (SF) and the superior temporal sulcus (STS) was traced in each hemisphere from three regions of the cerebral cortex. These three regions were labeled according to their position on the sagittal plane as lateral, medial and insular. It was hypothesized that the length and asymmetry of these fissures would be dependent on the region of measurement and that a leftward asymmetry in the SF and STS would be more robust in the great ape sample than for the monkeys. The results indicated within the ape sample a population-level leftward asymmetry in the medial and insular regions of the SF. Within the Old and New World monkey samples, the SF was leftward in the medial region at the population level, but not at the insular region. Additionally, the Old World monkeys exhibited a population-level rightward lateral SF and a rightward lateral STS. No other families exhibited population-level asymmetries in the lateral region of the SF or in any region of the STS. These results are consistent with findings reported in apes and, to a lesser extent, monkeys. MRI has excellent potential for comparing neuroanatomy across taxonomic families that will help future investigations. PMID:11326134

Differential modulation of endothelin ligand-induced contraction in isolated tracheae from endothelin B (ETB) receptor knockout mice

PubMed Central

Hay, Douglas W P; Douglas, Stephen A; Ao, Zhaohui; Moesker, Rodney M; Self, Glenn J; Rigby, Paul J; Luttmann, Mark A; Goldie, Roy G

2001-01-01

The role of endothelin B (ETB) receptors in mediating ET ligand-induced contractions in mouse trachea was examined in ETB receptor knockout animals.Autoradiographic binding studies, using [125I]-ET-1, confirmed the presence of ETA receptors in tracheal and bronchial airway smooth muscle from wild-type (+/+) and homozygous recessive (−/−) ETB receptor knockout mice. In contrast, ETB receptors were not detected in airway tissues from (−/−) mice.In tracheae from (+/+) mice, the rank order of potencies of the ET ligands was sarafotoxin (Stx) S6c>ET-1>ET-3; Stx S6c had a lower efficacy than ET-1 or ET-3. In tissues from (−/−) mice there was no response to Stx S6c (up to 0.1 μM), whereas the maximum responses and potencies of ET-1 and ET-3 were similar to those in (+/+) tracheae. ET-3 concentration-response curve was biphasic in (+/+) tissues (via ETA and ETB receptor activation), and monophasic in (−/−) preparations (via stimulation of only ETA receptors).In (+/+) preparations SB 234551 (1 nM), an ETA receptor-selective antagonist, inhibited the secondary phase, but not the first phase, of the ET-3 concentration-response curve, whereas A192621 (100 nM), an ETB receptor-selective antagonist, had the opposite effect. In (−/−) tissues SB 234551 (1 nM), but not A192621 (100 nM), produced a rightward shift in ET-3 concentration-response curves.The results confirm the significant influence of both ETA and ETB receptors in mediating ET-1-induced contractions in mouse trachea. Furthermore, the data do not support the hypothesis of atypical ETB receptors. In this preparation ET-3 is not an ETB receptor-selective ligand, producing contractions via activation of both ETA and ETB receptors. PMID:11309263

Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but preserved cAMP-dependent up-regulation.

PubMed

Spätjens, Roel L H M G; Bébarová, Markéta; Seyen, Sandrine R M; Lentink, Viola; Jongbloed, Roselie J; Arens, Yvonne H J M; Heijman, Jordi; Volders, Paul G A

2014-10-01

Mutations in KCNQ1, encoding for Kv7.1, the α-subunit of the IKs channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. K557E carriers had moderate QTc prolongation that augmented significantly during exercise. IKs characteristics were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary cells. K557E caused IKs loss of function with slowing of the activation kinetics, acceleration of deactivation kinetics, and a rightward shift of voltage-dependent activation. Together, these contributed to a dominant-negative reduction in IKs density. Confocal microscopy and western blot indicated that trafficking of K557E channels was not impaired. Stimulation of WT IKs by 3'-5'-cyclic adenosine monophosphate (cAMP) generated strong current up-regulation that was preserved for K557E in both hetero- and homozygosis. Accumulation of IKs at fast rates occurred both in WT and in K557E, but was blunted in the latter. In a computational model, K557E showed a loss of action potential shortening during β-adrenergic stimulation, in accordance with the lack of QT shortening during exercise in patients. K557E causes IKs loss of function with reduced fast rate-dependent current accumulation. cAMP-dependent stimulation of mutant IKs is preserved, but incapable of fully compensating for the baseline current reduction, explaining the long QT intervals at baseline and the abnormal QT accommodation during exercise in affected patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Antihypertensive activity of 80% methanol seed extract of Calpurnia aurea (Ait.) Benth. subsp. aurea (Fabaceae) is mediated through calcium antagonism induced vasodilation.

PubMed

Getiye, Yohannes; Tolessa, Tesfaye; Engidawork, Ephrem

2016-08-02

Calpurnia aurea (Ait.) Benth. subsp. aurea (CASA) (Fabaceae) seeds are used to treat hypertension in Ethiopian folklore medicine, particularly by Shinasha, Agew-awi and Amhara people in northwest Ethiopia. However, the claim has so far not been substantiated scientifically. The study was conducted to evaluate the antihypertensive activity of 80% methanol extract of CASA in animal model of hypertension as well as its vasorelaxant effect and possible underlying mechanisms in isolated guinea pig aorta. Hypotensive and antihypertensive effect of CASA extract was determined in vivo through the intravenous (iv) route in normotensive and hypertensive anesthetized rats using 2-kidney-1-clip (2K1C) rat model. Ex vivo, guinea pig thoracic aortic rings were isolated and suspended in organ bath, and the vasodepressor effects as well as the mechanism of action of the extract were studied by means of isometric tension recording experiments. The blood pressure fell dose-dependently and significantly in renal hypertensive and normotensive rats following i.v. administration, suggesting that the hydroalcoholic extract possesses hypotensive and antihypertensive effects. The extract also caused a dose-dependent relaxation of aorta pre-contracted with KCl at a concentration of 5-250mg/L, with a maximum relaxation of 92.1% achieved at 250mg/L. The relaxation mechanism was found to be independent of the muscarinic receptors, histamine receptors, ATP dependent K(+) channels, cyclooxygenase enzymes, cGMP/NO pathway and the endothelium system. The extract caused rightward shift of the Ca(++) dose-response curves, similar to that caused by verapamil, indicating that it produced vasorelaxation by inhibiting extracellular Ca(2+) influx. The findings demonstrate that the plant is endowed with antihypertensive effect, providing evidence for its traditional use. The effect may be, at least in part, due to dilation of blood vessels through blockage of Ca(2+) channels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Patterns of neural activity associated with differential acute locomotor stimulation to cocaine and methamphetamine in adolescent versus adult male C57BL/6J mice

PubMed Central

Zombeck, Jonathan A.; Lewicki, Aaron D.; Patel, Kevin; Gupta, Tripta; Rhodes, Justin S.

2009-01-01

Adolescence is a time period when major changes occur in the brain with long-term consequences for behavior. One ramification is altered responses to drugs of abuse, but the specific brain mechanisms and implications for mental health are poorly understood. Here, we used a mouse model in which adolescents display dramatically reduced sensitivity to the acute locomotor stimulating effects of cocaine and methamphetamine. The goal was to identify key brain regions or circuits involved in the differential behavior. Male adolescent (PN 30–35) and young adult (PN 69–74) C57BL/6J mice were administered an intraperitoneal injection of cocaine (0, 15, 30 mg/kg) or methamphetamine (0, 2, 4 mg/kg) and euthanized 90 minutes later. Locomotor activity was monitored continuously in the home cage by video tracking. Immunohistochemical detection of Fos protein was used to quantify neuronal activation in 16 different brain regions. As expected, adolescents were less sensitive to the locomotor stimulating effects of cocaine and methamphetamine as indicated by a rightward shift in the dose response relationship. After a saline injection, adolescents showed similar levels of Fos as adults in all regions except the dorsal and lateral caudate where levels were lower in adolescents. Cocaine and methamphetamine dose dependently increased Fos in all brain regions sampled in both adolescents and adults, but Fos levels were similar in both age groups for a majority of regions and doses. Locomotor activity was correlated with Fos in several brain areas within adolescent and adult groups, and adolescents had a significantly greater induction of Fos for a given amount of locomotor activity in key brain regions including the caudate where they showed reduced Fos under baseline conditions. Future research will identify the molecular and cellular events that are responsible for the differential psychostimulant-induced patterns of brain activation and behavior observed in adolescent versus adult mice. PMID:19932887

Warm-up Practices in Elite Boxing Athletes: Impact on Power Output.

PubMed

Cunniffe, Brian; Ellison, Mark; Loosemore, Mike; Cardinale, Marco

2017-01-01

Cunniffe, B, Ellison, M, Loosemore, M, and Cardinale, M. Warm-up practices in elite boxing athletes: Iimpact on power output. J Strength Cond Res 31(1): 95-105, 2017-This study evaluated the performance impact of routine warm-up strategies in elite Olympic amateur boxing athletes and physiological implications of the time gap (GAP) between warm-up and boxing activity. Six male boxers were assessed while performing standardized prefight warm-up routines. Core and skin temperature measurements (Tcore and Tskin), heart rate, and upper- and lower-body power output (PO) were assessed before and after warm-up, during a 25-minutes GAP and after 3 × 2 minutes rounds of sparring. Reflected temperature (Tc) was also determined using high-resolution thermal images at fixed time-points to explore avenues for heat loss. Despite individual differences in warm-up duration (range 7.4-18.5 minutes), increases in Tcore and Tskin occurred (p ≤ 0.05). Corresponding increases (4.8%; p ≤ 0.05) in countermovement jump (CMJ) height and upward-rightward shifts in upper-body force-velocity and power-velocity curves were observed. Athletes remained inactive during the 25-minutes GAP with a gradual and significant increase in Tc occurring by the end of GAP suggesting the likelihood of heat loss. Decreases in CMJ height and upper-body PO were observed after 15 minutes and 25 minutes GAP (p ≤ 0.05). By the end of GAP period, all performance variables had returned to pre-warm-up values. Results suggest routine warm-ups undertaken by elite boxers have acute effects on power-generating capacity. Gradual decreases in performance variables are evident with inactivity and seem related to alterations in body temperature. Considering the constraints of major competitions and time spent in air conditioned holding areas before fights, practitioners should be aware of the potential of nullifying the warm-up effects.

The beta-3 adrenoceptor agonist, mirabegron relaxes isolated prostate from human and rabbit: new therapeutic indication?

PubMed

Calmasini, Fabiano B; Candido, Tuany Z; Alexandre, Eduardo C; D'Ancona, Carlos A; Silva, Daniel; de Oliveira, Marco Antonio; De Nucci, Gilberto; Antunes, Edson; Mónica, Fabíola Z

2015-03-01

Alpha1 (α1)-blockers, 5-alpha reductase and phosphodiesterase type-5 inhibitors are pharmacological classes currently available for benign prostatic hyperplasia (BPH) treatment. Mirabegron, a beta-3 adrenoceptor (β3-AR) agonist has been approved for the therapy of overactive bladder and may constitute a new therapeutic option for BPH treatment. This study is aimed to evaluate the in vitro effects of mirabegron in human and rabbit prostatic smooth muscle. In rabbit prostate, electrical field stimulation (EFS)-induced contraction and concentration-response curve (CRC) to mirabegron in phenylephrine pre-contracted tissues were carried out. The potency (pEC50 ) and maximal response (Emax ) values were determined. In human prostate, CRC to phenylephrine was carried out in the absence and presence of mirabegron. Immunohistochemistry analysis for β3-AR was also carried out. In human prostate, immunohistochemistry analysis revealed the presence of β3-AR on the transition zone and mirabegron reduced by 42% the phenylephrine-induced contractions. In rabbit prostate, mirabegron produced concentration-dependent relaxations (pEC50 : 6.01 ± 0.12; Emax : 106 ± 3%), which were fully resistant to the blockade of β1-AR and β2-AR. The β3-AR blocker L748,337 caused a six-fold rightward shift in mirabegron-induced relaxations. Mirabegron (10 μM) reduced by 63% the EFS-induced contractions. Inhibitors of nitric oxide (L-NAME) and of soluble guanylate cyclase (ODQ) along with a cocktail of K+ channel blockers (apamin, charybdotoxin, glibenclamide, tetraethylammonium) all failed to significantly affect the mirabegron-induced rabbit relaxations. Mirabegron relaxes prostatic smooth muscle, providing an experimental support for the clinical investigation of its combination with an α1-blockers or PDE5 inhibitors in the treatment of BPH. Prostate 75:440-447, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Sulcal morphology and volume of Broca's area linked to handedness and sex.

PubMed

Powell, Joanne L; Kemp, Graham J; Roberts, Neil; García-Finaña, Marta

2012-06-01

We investigated the effect of handedness and sex on: (i) sulcal contours defining PO and PTR and (ii) volume estimates of PO and PTR subfields in 40 left- and 42 right-handers. Results show an effect of handedness on discontinuity of the inferior frontal sulcus (IFS: P<0.01). Discontinuity of IFS was observed in: 43% left- and 62% right hemispheres in right-handers and in 65% left- and 48% right-hemispheres in left-handers. PO volume asymmetry was rightward in left-handed males (P=0.007) and females (P=0.02), showed a leftward trend in right-handed males (P=0.06), and was non-asymmetrical in right-handed females (P=0.96, i.e. left- and right-hemisphere PO volumes did not differ significantly). PO volume asymmetry in males differed significantly between handedness groups (P=0.001). Findings indicate a high degree of variability in the sulcal contours of PO and PTR and volume asymmetry of PO: the factors sex and handedness can explain some of this variability. Copyright © 2012 Elsevier Inc. All rights reserved.

Positions of the cytoplasmic end of BK α S0 helix relative to S1–S6 and of β1 TM1 and TM2 relative to S0–S6

PubMed Central

Liu, Guoxia; Zakharov, Sergey I.; Yao, Yongneng

2015-01-01

The large-conductance, voltage- and Ca2+-gated K+ (BK) channel consists of four α subunits, which form a voltage- and Ca2+-gated channel, and up to four modulatory β subunits. The β1 subunit is expressed in smooth muscle, where it slows BK channel kinetics and shifts the conductance–voltage (G-V) curve to the left at [Ca2+] > 2 µM. In addition to the six transmembrane (TM) helices, S1–S6, conserved in all voltage-dependent K+ channels, BK α has a unique seventh TM helix, S0, which may contribute to the unusual rightward shift in the G-V curve of BK α in the absence of β1 and to a leftward shift in its presence. Such a role is supported by the close proximity of S0 to S3 and S4 in the voltage-sensing domain. Furthermore, on the extracellular side of the membrane, one of the two TM helices of β1, TM2, is adjacent to S0. We have now analyzed induced disulfide bond formation between substituted Cys residues on the cytoplasmic side of the membrane. There, in contrast, S0 is closest to the S2–S3 loop, from which position it is displaced on the addition of β1. The cytoplasmic ends of β1 TM1 and TM2 are adjacent and are located between the S2–S3 loop of one α subunit and S1 of a neighboring α subunit and are not adjacent to S0; i.e., S0 and TM2 have different trajectories through the membrane. In the absence of β1, 70% of disulfide bonding of W43C (S0) and L175C (S2–S3) has no effect on V50 for activation, implying that the cytoplasmic end of S0 and the S2–S3 loop move in concert, if at all, during activation. Otherwise, linking them together in one state would obstruct the transition to the other state, which would certainly change V50. PMID:25667410

Pyrethroid resistance alters the blood-feeding behavior in Puerto Rican Aedes aegypti mosquitoes exposed to treated fabric

PubMed Central

Bloomquist, Jeffrey R.; Bernier, Ulrich R.

2017-01-01

Emerging insecticide resistance is a major issue for vector control. It decreases the effectiveness of insecticides, thereby requiring greater quantities for comparable control with a net increase in risk of disease resurgence, product cost, and damage risk to the ecosystem. Pyrethroid resistance has been documented in Puerto Rican populations of Aedes aegypti (L.) mosquitoes. In this study, topical toxicity of five insecticides (permethrin, etofenprox, deltamethrin, DDT, transfluthrin) was determined for susceptible (Orlando—ORL) and resistant (Puerto Rico—PR) strains of Ae. aegypti. Resistance ratios were calculated using LD50 values, and high resistance ratios for permethrin (112) and etofenprox (228) were observed for the Puerto Rico strain. Behavioral differences in blood-feeding activity for pyrethroid-resistant and pyrethroid-susceptible strains of Ae. aegypti when exposed to pyrethroid-treated cloth were also explored. Strains were exposed for 15 min to a range of concentrations of pyrethroid-treated uniform fabric in a cage that contained 60 female Ae. aegypti mosquitoes. Interestingly, the resistance ratios for blood-feeding were similar for permethrin (61) and etofenprox (70), but were lower than their respective resistance ratios for topical toxicity, suggesting that knockdown resistance was the primary mechanism of resistance in the blood feeding assays. Results showed a rightward shift in the dose-response curves for blood-feeding that indicated higher concentrations of pyrethroids were necessary to deter blood-feeding behavior in the pyrethroid-resistant Puerto Rican strain of Ae. aegypti. PMID:28931018

A Simple and Rapid Method for Standard Preparation of Gas Phase Extract of Cigarette Smoke

PubMed Central

Higashi, Tsunehito; Mai, Yosuke; Noya, Yoichi; Horinouchi, Takahiro; Terada, Koji; Hoshi, Akimasa; Nepal, Prabha; Harada, Takuya; Horiguchi, Mika; Hatate, Chizuru; Kuge, Yuji; Miwa, Soichi

2014-01-01

Cigarette smoke consists of tar and gas phase: the latter is toxicologically important because it can pass through lung alveolar epithelium to enter the circulation. Here we attempt to establish a standard method for preparation of gas phase extract of cigarette smoke (CSE). CSE was prepared by continuously sucking cigarette smoke through a Cambridge filter to remove tar, followed by bubbling it into phosphate-buffered saline (PBS). An increase in dry weight of the filter was defined as tar weight. Characteristically, concentrations of CSEs were represented as virtual tar concentrations, assuming that tar on the filter was dissolved in PBS. CSEs prepared from smaller numbers of cigarettes (original tar concentrations ≤15 mg/ml) showed similar concentration-response curves for cytotoxicity versus virtual tar concentrations, but with CSEs from larger numbers (tar ≥20 mg/ml), the curves were shifted rightward. Accordingly, the cytotoxic activity was detected in PBS of the second reservoir downstream of the first one with larger numbers of cigarettes. CSEs prepared from various cigarette brands showed comparable concentration-response curves for cytotoxicity. Two types of CSEs prepared by continuous and puff smoking protocols were similar regarding concentration-response curves for cytotoxicity, pharmacology of their cytotoxicity, and concentrations of cytotoxic compounds. These data show that concentrations of CSEs expressed by virtual tar concentrations can be a reference value to normalize their cytotoxicity, irrespective of numbers of combusted cigarettes, cigarette brands and smoking protocols, if original tar concentrations are ≤15 mg/ml. PMID:25229830

Lateralization of posterior alpha EEG reflects the distribution of spatial attention during saccadic reading.

PubMed

Kornrumpf, Benthe; Dimigen, Olaf; Sommer, Werner

2017-06-01

Visuospatial attention is an important mechanism in reading that governs the uptake of information from foveal and parafoveal regions of the visual field. However, the spatiotemporal dynamics of how attention is allocated during eye fixations are not completely understood. The current study explored the use of EEG alpha-band oscillations to investigate the spatial distribution of attention during reading. We reanalyzed two data sets, focusing on the lateralization of alpha activity at posterior scalp sites. In each experiment, participants read short lists of German nouns in two paradigms: either by freely moving their eyes (saccadic reading) or by fixating the screen center while the text moved passively from right to left at the same average speed (RSVP paradigm). In both paradigms, upcoming words were either visible or masked, and foveal processing load was manipulated by varying the words' lexical frequencies. Posterior alpha lateralization revealed a sustained rightward bias of attention during saccadic reading, but not in the RSVP paradigm. Interestingly, alpha lateralization was not influenced by word frequency (foveal load) or preview during the preceding fixation. Hence, alpha did not reflect transient attention shifts within a given fixation. However, in both experiments, we found that in the saccadic reading condition a stronger alpha lateralization shortly before a saccade predicted shorter fixations on the subsequently fixated word. These results indicate that alpha lateralization can serve as a measure of attention deployment and its link to oculomotor behavior in reading. © 2017 Society for Psychophysiological Research.

Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury

PubMed Central

Duthie, Karolina M; Hadoke, Patrick W F; Kirkby, Nicholas S; Miller, Eileen; Ivy, Jessica R; McShane, John F; Lim, Win Gel; Webb, David J

2015-01-01

Background and Purpose Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA/B receptor antagonism at inhibiting neointimal proliferation in a mouse model of intraluminal injury. Experimental Approach Antagonism of ETA receptors by sitaxentan (1–100 nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15 mg·kg−1·day−1), A192621 (ETB antagonist; 30 mg·kg−1·day−1), the combination of both antagonists or vehicle. Treatment began 1 week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Key Results Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA/B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions. Conclusions and Implications These results suggest that ETA receptor antagonism would be more effective than combined ETA/ETB receptor antagonism at reducing neointimal lesion formation. PMID:25598351

The idea of uniform change: is it time to revisit a central tenet of Rose's "Strategy of Preventive Medicine"?

PubMed

Razak, Fahad; Davey Smith, George; Subramanian, S V

2016-12-01

A mean-centric view of populations, whereby a change in the mean of a health variable at the population level is assumed to result in uniform change across the distribution, is a core component of Geoffrey Rose's concept of the "population strategy" to disease prevention. This idea also has a critical role in Rose's observation that individuals who are considered abnormal or sick (the rightward tail of the distribution) and those who are considered normal (the center) are very closely related, and that true preventive medicine must focus on shifting the normal or average. In this Perspective, we revisit these core tenets of Rose's concept of preventive medicine after providing an overview of the key concepts that he developed. We examine whether these assumptions apply to population changes in body mass index (BMI) and show that there is considerable evidence of a widening of the BMI distribution in populations over time. We argue that, with respect to BMI, the idea of using statistical measures of a population solely on the basis of means and the assumption that populations are coherent entities that change uniformly over time may not fully capture the true nature of changes in the population. These issues have important implications for how we assess and interpret the health of populations over time with implications for the balance between universal and targeted strategies aimed at improving health. © 2016 American Society for Nutrition.

Therapeutic implications of Epstein–Barr virus infection for the treatment of nasopharyngeal carcinoma

PubMed Central

Hutajulu, Susanna Hilda; Kurnianda, Johan; Tan, I Bing; Middeldorp, Jaap M

2014-01-01

Nasopharyngeal carcinoma (NPC) is highly endemic in certain regions including the People’s Republic of China and Southeast Asia. Its etiology is unique and multifactorial, involving genetic background, epigenetic, and environment factors, including Epstein–Barr virus (EBV) infection. The presence of EBV in all tumor cells, aberrant pattern of antibodies against EBV antigens in patient sera, and elevated viral DNA in patient circulation as well as nasopharyngeal site underline the role of EBV during NPC development. In NPC tumors, EBV expresses latency type II, where three EBV-encoded proteins, Epstein–Barr nuclear antigen 1, latent membrane protein 1 and 2 (LMP1, 2), are expressed along with BamH1-A rightward reading frame 1, Epstein–Barr virus-encoded small nuclear RNAs, and BamH1-A rightward transcripts. Among all encoded proteins, LMP1 plays a central role in the propagation of NPC. Standard treatment of NPC consists of radiotherapy with or without chemotherapy for early stage, concurrent chemoradiotherapy in locally advanced tumors, and palliative systemic chemotherapy in metastatic disease. However, this standard care has limitations, allowing recurrences and disease progression in a certain proportion of cases. Although the pathophysiological link and molecular process of EBV-induced oncogenesis are not fully understood, therapeutic approaches targeting the virus may increase the cure rate and add clinical benefit. The promising results of early phase clinical trials on EBV-specific immunotherapy, epigenetic therapy, and treatment with viral lytic induction offer new options for treating NPC. PMID:25228810

Language-dependent changes in pitch-relevant neural activity in the auditory cortex reflect differential weighting of temporal attributes of pitch contours

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Xu, Yi; Suresh, Chandan H.

2016-01-01

There remains a gap in our knowledge base about neural representation of pitch attributes that occur between onset and offset of dynamic, curvilinear pitch contours. The aim is to evaluate how language experience shapes processing of pitch contours as reflected in the amplitude of cortical pitch-specific response components. Responses were elicited from three nonspeech, bidirectional (falling-rising) pitch contours representative of Mandarin Tone 2 varying in location of the turning point with fixed onset and offset. At the frontocentral Fz electrode site, Na–Pb and Pb–Nb amplitude of the Chinese group was larger than the English group for pitch contours exhibiting later location of the turning point relative to the one with the earliest location. Chinese listeners’ amplitude was also greater than that of English in response to those same pitch contours with later turning points. At lateral temporal sites (T7/T8), Na–Pb amplitude was larger in Chinese listeners relative to English over the right temporal site. In addition, Pb–Nb amplitude of the Chinese group showed a rightward asymmetry. The pitch contour with its turning point located about halfway of total duration evoked a rightward asymmetry regardless of group. These findings suggest that neural mechanisms processing pitch in the right auditory cortex reflect experience-dependent modulation of sensitivity to weighted integration of changes in acceleration rates of rising and falling sections and the location of the turning point. PMID:28713201

Non-spatial neglect for the mental number line.

PubMed

van Dijck, Jean-Philippe; Gevers, Wim; Lafosse, Christophe; Doricchi, Fabrizio; Fias, Wim

2011-07-01

Several psychophysical investigations, expanding the classical introspective observations by Galton, have suggested that the mental representation of numbers takes the form of a number line along which magnitude is positioned in ascending order according to reading habits, i.e. from left to right in Western cultures. In keeping with the evidence, pathological rightward deviations in the bisection of number intervals due to right brain damage are generally interpreted as originating from a purely spatial-attentional deficit in the processing of the left side of number intervals. However, consistent double dissociations between defective processing of the left side of physical and mental number space have called into question the universality of this interpretation. Recent evidence suggests a link between rightward deviations in number space and defective memory for both spatial and non-spatial sequences of items. Here we describe the case of a left brain-damaged patient exhibiting right-sided neglect for extrapersonal and representational space, and left-sided neglect on the mental number line. Accurate neuropsychological examination revealed that the apparent left-sided neglect in the bisection of number intervals had a purely non-spatial origin and was based on mnemonic difficulties for the initial items of verbal sequences presented visually at an identical spatial position. These findings show that effective position-based verbal working memory might be crucial for numerical tasks that are usually considered to involve purely spatial representation of numerical magnitudes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study.

PubMed

Vallar, Giuseppe; Bello, Lorenzo; Bricolo, Emanuela; Castellano, Antonella; Casarotti, Alessandra; Falini, Andrea; Riva, Marco; Fava, Enrica; Papagno, Costanza

2014-04-01

To assess the role of the superior longitudinal fascicle, the inferior fronto-occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery. Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection. A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective. The parietofrontal connections of the dorso-lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure. Copyright © 2013 Wiley Periodicals, Inc.

Perceived direction of gravity and the body-axis during static whole body roll-tilt in healthy subjects.

PubMed

Tamura, Atsushi; Wada, Yoshiro; Inui, Takuo; Shiotani, Akihiro

2017-10-01

We used the subjective visual vertical (SVV) and two different subjective visual body axis (SVBA) methods to quantify roll-tilt perception under gravity, and investigated the characteristics of these methods during static roll-tilt. In addition, we independently developed a compact device to facilitate evaluation of SVBA in different gravitational environments. Ten male volunteers participated in this study. We created a roll-tilt environment using a flight simulator in a dark room. The cockpit of the simulator was tilted leftward or rightward (-30°, -20°, -10°, 0°, 10°, 20° and 30°) in each randomly ordered trial. We quantified roll-tilt perception such that the experiment was conducted under 21 different conditions per participant. We found no significant differences among the SVV error and the two types of SVBA error. The SVV and the SVBA methods may be useful for evaluating subjective roll-tilt perception.

Competitive antagonists discriminate between NK2 tachykinin receptor subtypes.

PubMed

Maggi, C A; Patacchini, R; Giuliani, S; Rovero, P; Dion, S; Regoli, D; Giachetti, A; Meli, A

1990-07-01

1. We have compared the ability of various tachykinins and selective tachykinin receptor agonists to induce contraction of the endothelium-denuded rabbit pulmonary artery (RPA) and hamster trachea (HT) and have estimated the affinity of some newly developed NK2 selective antagonists in the same tissues. 2. In confirmation of previous findings, experiments with the agonists indicated that NK2 receptors are the main if not the sole mediators of the response to tachykinins in both RPA and HT. No evidence for significant degradation of neurokinin A (NKA) was found in either tissue when experiments were repeated in the presence of a mixture of peptidase inhibitors (thiorphan, captopril and bestatin, 1 microM each). 3. The peptide antagonists tested were: Peptide I = [Tyr5, D-Trp6,8,9, Arg10]-NKA(4-10); Peptide II = [Tyr5, D-Trp6,8,9, Arg10]-NKA(3-10); Peptide III = Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2. The three peptides produced a concentration-dependent rightward shift of the concentration-response curve to NKA in both RPA and HT with no significant depression of the maximal response attainable. The slopes of the Schild plots were not significantly different from unity, indicating a competitive antagonism. Peptides I and II were about 100 times more potent in the RPA than in the HT, while Peptide III was about 100 times more potent in the HT than RPA. 4. The pA2 values obtained in these two tissues with the three antagonists were not significantly different when tested in the absence or presence of peptidase inhibitors, or when a selective NK2 receptor agonist, [beta Ala8]-NKA(4-10) was used instead of NKA. Similar pA2 values were obtained after 15 or 90min of incubation with the antagonists. Peptides I, II and III had no inhibitory effect on contractions produced by noradrenaline in the RPA or by carbachol in the HT. 5. Peptides I, II and III showed weak or no antagonistic activity toward the vasodilatator effect of substance P in the dog carotid artery (NK, receptor-mediated) or toward the contractile effect of neurokinin B in the rat portal vein (NK3 receptor-mediated). 6. These results provide pharmacological evidence for heterogeneity of NK2 receptors in the RPA and HT. The NK2 receptors present in these tissues are not discriminated by natural tachykinins or selective agonists, but are recognized with very different affinity by NK2 receptor antagonists.

Gravitoinertial force background level affects adaptation to coriolis force perturbations of reaching movements

NASA Technical Reports Server (NTRS)

Lackner, J. R.; Dizio, P.

1998-01-01

We evaluated the combined effects on reaching movements of the transient, movement-dependent Coriolis forces and the static centrifugal forces generated in a rotating environment. Specifically, we assessed the effects of comparable Coriolis force perturbations in different static force backgrounds. Two groups of subjects made reaching movements toward a just-extinguished visual target before rotation began, during 10 rpm counterclockwise rotation, and after rotation ceased. One group was seated on the axis of rotation, the other 2.23 m away. The resultant of gravity and centrifugal force on the hand was 1.0 g for the on-center group during 10 rpm rotation, and 1.031 g for the off-center group because of the 0.25 g centrifugal force present. For both groups, rightward Coriolis forces, approximately 0.2 g peak, were generated during voluntary arm movements. The endpoints and paths of the initial per-rotation movements were deviated rightward for both groups by comparable amounts. Within 10 subsequent reaches, the on-center group regained baseline accuracy and straight-line paths; however, even after 40 movements the off-center group had not resumed baseline endpoint accuracy. Mirror-image aftereffects occurred when rotation stopped. These findings demonstrate that manual control is disrupted by transient Coriolis force perturbations and that adaptation can occur even in the absence of visual feedback. An increase, even a small one, in background force level above normal gravity does not affect the size of the reaching errors induced by Coriolis forces nor does it affect the rate of reacquiring straight reaching paths; however, it does hinder restoration of reaching accuracy.

Video quality assessment based on correlation between spatiotemporal motion energies

NASA Astrophysics Data System (ADS)

Yan, Peng; Mou, Xuanqin

2016-09-01

Video quality assessment (VQA) has been a hot research topic because of rapid increase of huge demand of video communications. From the earliest PSNR metric to advanced models that are perceptual aware, researchers have made great progress in this field by introducing properties of human vision system (HVS) into VQA model design. Among various algorithms that model the property of HVS perceiving motion, the spatiotemporal energy model has been validated to be high consistent with psychophysical experiments. In this paper, we take the spatiotemporal energy model into VQA model design by the following steps. 1) According to the pristine spatiotemporal energy model proposed by Adelson et al, we apply the linear filters, which are oriented in space-time and tuned in spatial frequency, to filter the reference and test videos respectively. The outputs of quadrature pairs of above filters are then squared and summed to give two measures of motion energy, which are named rightward and leftward energy responses, respectively. 2) Based on the pristine model, we calculate summation of the rightward and leftward energy responses as spatiotemporal features to represent perceptual quality information for videos, named total spatiotemporal motion energy maps. 3) The proposed FR-VQA model, named STME, is calculated with statistics based on the pixel-wise correlation between the total spatiotemporal motion energy maps of the reference and distorted videos. The STME model was validated on the LIVE VQA Database by comparing with existing FR-VQA models. Experimental results show that STME performs with excellent prediction accuracy and stays in state-of-the-art VQA models.

Dominant vs. nondominant arm advantage in mentally simulated actions in right handers.

PubMed

Gandrey, Philippe; Paizis, Christos; Karathanasis, Vassilis; Gueugneau, Nicolas; Papaxanthis, Charalambos

2013-12-01

Although plentiful data are available regarding mental states involving the dominant-right arm, the evidence for the nondominant-left arm is sparse. Here, we investigated whether right-handers can generate accurate predictions with either the right or the left arm. Fifteen adults carried out actual and mental arm movements in two directions with varying inertial resistance (inertial anisotropy phenomenon). We recorded actual and mental movement times and used the degree of their similarity as an indicator for the accuracy of motor imagery/prediction process. We found timing correspondences (isochrony) between actual and mental right arm movements in both rightward (low inertia resistance) and leftward (high inertia resistance) directions. Timing similarities between actual and mental left arm movements existed for the leftward direction (low inertia resistance) but not for the rightward direction (high inertia resistance). We found similar results when participants reaching towards the midline of the workspace, a result that excludes a hemispace effect. Electromyographic analysis during mental movements showed that arm muscles remained inactivate, thus eliminating a muscle activation strategy that could explain intermanual differences. Furthermore, motor-evoked potentials enhancement in both right and left biceps brachii during mental actions indicated that subjects were actively engaged in mental movement simulation and that the disadvantage of the left arm cannot be attributed to the nonactivation of the right motor cortex. Our findings suggest that predictive mechanisms are more robust for the right than the left arm in right-handers. We discussed these findings from the perspective of the internal models theory and the dynamic-dominance hypothesis of laterality.

Schedule-induced polydipsia in the spontaneously hypertensive rat and its relation to impulsive behaviour.

PubMed

Ibias, Javier; Pellón, Ricardo

2011-09-30

Eight Spontaneously Hypertensive Rat (SHR), 8 Wistar-Kyoto (WKY) and 8 Wistar rats, all male, maintained at 80-85% of their free-feeding weight by controlled access to food, were exposed to a series of fixed time (FT) schedules whereby food pellets were regularly delivered regardless of the animals' behaviour. The FT values used were 9, 15, 30, 60, 120 and 180 s, with the order of presentation of the schedules among the animals being counterbalanced (except under the FT 120-s and 180-s schedules, which were successively presented as the last two of the series). Due to freely available access to water, the animals developed schedule-induced drinking under all FT schedules, marked by the characteristic bitonic function that relates the number of licks and amount of water drunk to the length of the inter-food interval. Wistar and WKY rats displayed maximum drinking under an FT 15-s schedule, with WKY rats registering lower quantities across all FT values. Among SHR rats, maximum schedule-induced polydipsia was observed under the FT 30-s schedule, with a rightward shift in the bitonic function compared to controls. For long FT values, the temporal distribution of licks within inter-food intervals was shifted slightly towards the right in the SHR rats. In a subsequent study, only the SHR and Wistar rats were used, and the animals were exposed to a delay-discounting procedure. The rats were faced with successive choices, in which they could choose between an immediate reward of one food pellet and another of four food pellets at a delay of 3, 6, 12 or 24s. In the case of the longer delays, SHR rats chose the immediate reward of lower magnitude more often than did their Wistar counterparts, and also committed a greater number of omissions during the forced-choice trials of the procedure. The results indicate that differences in schedule-induced polydipsia are related to indexes of cognitive rather than motor impulsivity, a finding in line with the theoretical idea that adjunctive behaviour is linked to operant reinforcement processes. Copyright © 2011 Elsevier B.V. All rights reserved.

Steady-state [Ca2+]i-force relationship in intact twitching cardiac muscle: direct evidence for modulation by isoproterenol and EMD 53998.

PubMed Central

Dobrunz, L E; Backx, P H; Yue, D T

1995-01-01

We have developed a novel method for measuring steady-state force-[Ca2+]i relations in isolated, membrane-intact rat trabeculae that are microinjected with Fura-2 salt. Twitches are markedly slowed after inhibition of phasic Ca2+ release and uptake from the sarcoplasmic reticulum by addition of cyclopiazonic acid and ryanodine. During relaxation of slowed twitches, force and [Ca2+]i trace a common trajectory in plots of force versus [Ca2+]i, despite very different histories of contraction. The common trajectory thereby provides a high resolution determination of the steady-state relation between force and [Ca2+]i. Using this method, we show that 1 microM isoproterenol, a beta-adrenergic agonist, causes a rightward shift (Hill function K1/2 increased from 0.39 +/- 0.07 microM to 0.82 +/- 0.23 microM, p < 0.02, n = 6) and a decreased slope (nH decreased from 5.4 +/- 1.1 to 4.0 +/- 1.4, p < 0.02) of the steady-state force-[Ca2+]i curve, with no change in maximal force (Fmax = 99.2 +/- 2.2% of control). In contrast, 2 microM EMD 53998, a racemic thiadiazinone derivative, causes a leftward shift (K1/2 decreased from 0.42 +/- 0.02 microM to 0.30 +/- 0.06 microM, p < 0.02, n = 4) with no change in slope of the steady-state force-[Ca2+]i curve, accompanied by a modest increase in maximal force (Fmax = 107.1 +/- 4.6% of control, p < 0.02). To gain mechanistic insight into these modulatory events, we developed a simple model of cooperative thin filament activation that predicts steady-state force-[Ca2+]i relationships. Model analysis suggests that isoproterenol decreases cooperativity arising from nearest-neighbor interactions between regulatory units on the thin filament, without change in the equilibrium constant for Ca2+ binding. In contrast, the effects of EMD 53998 are consistent with an increase in the affinity of strong-binding cross-bridges, without change in either the affinity of troponin C for Ca2+ or cooperative interactions. PMID:7669896

Spasmolytic effect of aqueous extract of Tagetes erecta L. flowers is mediated through calcium channel blockade on the guinea-pig ileum.

PubMed

Ventura-Martínez, Rosa; Ángeles-López, Guadalupe E; Rodríguez, Rodolfo; González-Trujano, Ma Eva; Déciga-Campos, Myrna

2018-07-01

This study provides pharmacological evidence on the spasmolytic activity of Tagetes erecta L. (marigold or cempasúchil) on the guinea-pig ileum and presents data on its mechanism of action. The relaxant effect on KCl contractions was more marked with aqueous (AqEx) than with ethanol extracts (EtEx) of T. erecta flowers (55.6 ± 11.0 vs 21.1 ± 4.4%, respectively). In addition, the aqueous extract antagonized contractions elicited by EFS, but not by acetylcholine (73.5 ± 1.9 vs 14.5 ± 5.3%, respectively). These effects were not diminished by hexamethonium or L-NAME, but this extract caused a rightward shift in the Ca 2+ concentration-response curves like that of verapamil. Quercetin and rutin, two flavonoids present in this plant, also showed spasmolytic effects (95.7 ± 2.8 and 27.9 ± 7.1%, respectively). Interestingly, in tissues without spasmogens, the extract induced contractions superimposed on their spontaneous activity. These results support the traditional use of T. erecta as a spasmolytic in folk medicine and suggest mainly that quercetin could be partly responsible for this effect. The spasmolytic effect appears to involve voltage-gated calcium channels, but not the nitric oxide pathway or the release of neurotransmitters from enteric neurons. Nevertheless, this plant could produce colic or stomachache as adverse effects in clinical situations in which these symptoms are not originally present. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

PubMed Central

Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

An Experimental Itch Model in Monkeys

PubMed Central

Ko, M. C. Holden; Naughton, Norah N.

2007-01-01

Background The most common side effect of spinal opioid administration is pruritus, which has been treated with a variety of agents with variable success. Currently, there are few animal models developed to study this side effect. The aim of this study was to establish a nonhuman primate model to pharmacologically characterize the effects of intrathecal administration of morphine. Methods Eight adult rhesus monkeys were used. Scratching responses were videotaped and counted by observers who were blinded to experimental conditions. Antinociception was measured by a warm-water (50°C) tail-withdrawal assay. The dose-response of intrathecal morphine (1-320 μg) for both scratching and antinociception in all subjects was established. An opioid antagonist, nalmefene, was administered either intravenously or subcutaneously to assess its efficacy against intrathecal morphine. Results Intrathecal morphine (1-32 μg) increased scratching in a dose-dependent manner. Higher doses of intrathecal morphine (10-100 μg) produced thermal antinociception in a dose-dependent manner. On the other hand, nalmefene (10-32 μg/kg intravenously) attenuated maximum scratching responses among subjects. Pretreatment with nalmefene (32μg/kg subcutaneously) produced approximately 10-fold rightward shifts of intrathecal morphine dose-response curves for both behavioral effects. Conclusions These data indicate that intrathecal morphine-induced scratching and antinociception are mediated by opioid receptors. The magnitude of nalmefene antagonism of intrathecal morphine is consistent with μ opioid receptor mediation. This experimental itch model is useful for evaluating different agents that may suppress scratching without interfering with antinociception. It may also facilitate the clarification of mechanisms underlying these phenomena. PMID:10719958

Tachykinin receptors in the guinea-pig isolated bronchi.

PubMed

Maggi, C A; Patacchini, R; Quartara, L; Rovero, P; Santicioli, P

1991-05-17

The aim of the study was to assess which tachykinin receptors mediate the contractile response in the guinea-pig isolated bronchi. Experiments with natural tachykinins and receptor-selective tachykinin agonists were performed in the absence or presence of peptidase inhibitors and in bronchi pretreated with phenoxybenzamine. Both NK-1 (substance P, substance P methylester and septide) and NK-2 (neurokinin A, [beta-Ala8]neurokinin A-(4-10) and MDL 28,564) receptor agonists produced concentration-dependent contraction. NK-3 agonists (senktide and [MePhe7]neurokinin B) were active only at high concentrations. Phenoxybenzamine pretreatment reduced the maximal response to NK-1 agonists and produced a rightward shift of the curve to NK-2 agonists, without depression of the maximum. Five tachykinin antagonists selective for the NK-1 (L 668,169) or the NK-2 (MEN 10,207, MEN 10,376, L 659,877 and R 396) receptor were tested against substance P methylester and [beta-Ala8]neurokinin A-(4-10). The results indicated that these receptor-selective antagonists maintain their characteristic even when tested in a multireceptor assay such as the guinea-pig bronchus. The rank order of potency of NK-2 antagonists against [beta-Ala8]neurokinin A-(4-10) was MEN 10,207 = MEN 10,376 greater than L 659,877 much greater than R 396. This pattern, with the observation of the full agonist activity of MDL 28,564, indicates that in addition to NK-1 receptors, NK-2 receptors also are present in the guinea-pig bronchi and belong to the same subtype (NK-2A) as present in the rabbit pulmonary artery.

The perceptual processing capacity of summary statistics between and within feature dimensions

PubMed Central

Attarha, Mouna; Moore, Cathleen M.

2015-01-01

The simultaneous–sequential method was used to test the processing capacity of statistical summary representations both within and between feature dimensions. Sixteen gratings varied with respect to their size and orientation. In Experiment 1, the gratings were equally divided into four separate smaller sets, one of which with a mean size that was larger or smaller than the other three sets, and one of which with a mean orientation that was tilted more leftward or rightward. The task was to report the mean size and orientation of the oddball sets. This therefore required four summary representations for size and another four for orientation. The sets were presented at the same time in the simultaneous condition or across two temporal frames in the sequential condition. Experiment 1 showed evidence of a sequential advantage, suggesting that the system may be limited with respect to establishing multiple within-feature summaries. Experiment 2 eliminates the possibility that some aspect of the task, other than averaging, was contributing to this observed limitation. In Experiment 3, the same 16 gratings appeared as one large superset, and therefore the task only required one summary representation for size and another one for orientation. Equal simultaneous–sequential performance indicated that between-feature summaries are capacity free. These findings challenge the view that within-feature summaries drive a global sense of visual continuity across areas of the peripheral visual field, and suggest a shift in focus to seeking an understanding of how between-feature summaries in one area of the environment control behavior. PMID:26360153

Torque decrease during submaximal evoked contractions of the quadriceps muscle is linked not only to muscle fatigue.

PubMed

Matkowski, Boris; Lepers, Romuald; Martin, Alain

2015-05-01

The aim of this study was to analyze the neuromuscular mechanisms involved in the torque decrease induced by submaximal electromyostimulation (EMS) of the quadriceps muscle. It was hypothesized that torque decrease after EMS would reflect the fatigability of the activated motor units (MUs), but also a reduction in the number of MUs recruited as a result of changes in axonal excitability threshold. Two experiments were performed on 20 men to analyze 1) the supramaximal twitch superimposed and evoked at rest during EMS (Experiment 1, n = 9) and 2) the twitch response and torque-frequency relation of the MUs activated by EMS (Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that evoked 20% of the maximal voluntary contraction (MVC) torque. The same stimulation intensity delivered over the muscles was used to induce the torque-frequency relation and the single electrical pulse evoked after each EMS contraction (Experiment 2). In Experiment 1, supramaximal twitch was induced by femoral nerve stimulation. Torque decreased by ~60% during EMS-evoked contractions and by only ~18% during MVCs. This was accompanied by a rightward shift of the torque-frequency relation of MUs activated and an increase of the ratio between the superimposed and posttetanic maximal twitch evoked during EMS contraction. These findings suggest that the torque decrease observed during submaximal EMS-evoked contractions involved muscular mechanisms but also a reduction in the number of MUs recruited due to changes in axonal excitability. Copyright © 2015 the American Physiological Society.

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin-ethanolamides) in the feline iris.

PubMed

Woodward, D F; Krauss, A H; Wang, J W; Protzman, C E; Nieves, A L; Liang, Y; Donde, Y; Burk, R M; Landsverk, K; Struble, C

2007-02-01

The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2alpha and the prostamide F2alpha analog bimatoprost but did not block the effects of PGF2alpha and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.

The Prion Protein Modulates A-type K+ Currents Mediated by Kv4.2 Complexes through Dipeptidyl Aminopeptidase-like Protein 6*

PubMed Central

Mercer, Robert C. C.; Ma, Li; Watts, Joel C.; Strome, Robert; Wohlgemuth, Serene; Yang, Jing; Cashman, Neil R.; Coulthart, Michael B.; Schmitt-Ulms, Gerold; Jhamandas, Jack H.; Westaway, David

2013-01-01

Widely expressed in the adult central nervous system, the cellular prion protein (PrPC) is implicated in a variety of processes, including neuronal excitability. Dipeptidyl aminopeptidase-like protein 6 (DPP6) was first identified as a PrPC interactor using in vivo formaldehyde cross-linking of wild type (WT) mouse brain. This finding was confirmed in three cell lines and, because DPP6 directs the functional assembly of K+ channels, we assessed the impact of WT and mutant PrPC upon Kv4.2-based cell surface macromolecular complexes. Whereas a Gerstmann-Sträussler-Scheinker disease version of PrP with eight extra octarepeats was a loss of function both for complex formation and for modulation of Kv4.2 channels, WT PrPC, in a DPP6-dependent manner, modulated Kv4.2 channel properties, causing an increase in peak amplitude, a rightward shift of the voltage-dependent steady-state inactivation curve, a slower inactivation, and a faster recovery from steady-state inactivation. Thus, the net impact of wt PrPC was one of enhancement, which plays a critical role in the down-regulation of neuronal membrane excitability and is associated with a decreased susceptibility to seizures. Insofar as previous work has established a requirement for WT PrPC in the Aβ-dependent modulation of excitability in cholinergic basal forebrain neurons, our findings implicate PrPC regulation of Kv4.2 channels as a mechanism contributing to the effects of oligomeric Aβ upon neuronal excitability and viability. PMID:24225951

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

PubMed Central

Schipke, J. D.; Korbmacher, B.; Dorszewski, A.; Selcan, G.; Sunderdiek, U.; Arnold, G.

1996-01-01

OBJECTIVE--To amplify the description of myocardial stunning. DESIGN--Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS--15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES--Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS--Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS--Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus. Images PMID:8624873

The analgesic, anti-inflammatory and calcium antagonist potential of Tanacetum artemisioides.

PubMed

Bukhari, Ishfaq Ali; Khan, Rafeeq Alam; Gilani, Anwar-ul Hassan; Shah, Abdul Jabbar; Hussain, Javid; Ahmad, Viqar Uddin

2007-03-01

Several species of the genus Tanacetum are traditionally used in a variety of health conditions including pain, inflammation, respiratory and gastrointestinal disorders. In the current investigation, we evaluated the plant extract of T. artemisioides and some of its pure compounds (flavonoids) for analgesic, anti-inflammatory and calcium antagonist effects in various in-vivo and in vitro studies. Using the actetic acid induced writhing test, intraperitoneal (i.p) administration of the plant extract (25-50 mg/kg) and its flavonoid compounds TA-1 and TA-2 (1-5 mg/kg ) exhibited significant analgesic actvity. The maximum analgesic effect observed with the crude extract of the plant was 71% at 50 mg/kg, while that of compounds TA-1 and TA-2 (5 mg/kg i.p) was 75 and 47%, respectively. The plant extract and its pure compounds caused inhbition of formalin induced paw licking in mice predominatly in the second phase of the test. Diclofenac sodium, a standard reference compound, showed a simlar effect in these chemical induced pain models. In the carrgeenan induced rat paw edema assay, the plant extract (50-200 mg/kg i.p) demonstrated significant (P< 0.01) anti-inflammatory activity which was comparable to that obtained with diclofenac sodium and indomethacin. In isolated rabbit jejunum preprations the plant extract showed an atropine sensitive dose-dependent (0.10-1.0 mg/mL) spasmogenic activity followed by a spasmolytic effect at the next higher doses (3-5 mg/mL). The crude extract of the plant also inhibited the high K+-induced contractions, indicating a calcium channel blocking (CCB) activity, which was further confirmed when the plant extract caused a rightward shift in the Ca++ concentration response curves in the isolated rabbit jejunum preparations, similar to that seen with verapamil. The flavonoid compounds isolated from the plant were devoid of any activity in the isolated tissue preparations. These results indicate that the plant extract of T. artemisioides possesses analgesic, anti-inflammatory and CCB activities. The flavonoid compounds of the plant may have a role in its observed analgesic and antiinflammatory activities, while the CCB activity of the plant may be attributed to some other chemical constituents present. Moreover the findings support the traditional reputation of the genus Tanacetum for its therapeutic benefits in pain and inflammatory conditions.

On the instability and constraints of the interaction between number representation and spatial attention in healthy humans: A concise review of the literature and new experimental evidence.

PubMed

Fattorini, E; Pinto, M; Merola, S; D'Onofrio, M; Doricchi, F

2016-01-01

The relationship between number and space representation is still one of the most debated topics in studies of mathematical cognition. Here we offer a concise review of two important behavioral effects that have pointed out the use of a spatially left-to-right oriented mental number line (MNL) in healthy participants: the SNARC effect and the attentional SNARC effect (Att-SNARC). Following a brief summary of seminal investigations on the introspective properties of the MNL, we review recent empirical evidence and theories on the functional origin of the SNARC effect, where upon left/right response choices faster reaction times are found for small numbers with left-side responses and for large numbers with right-side responses. Then we offer a summary of the studies that have investigated whether the mere perception of visual Arabic numbers presented at central fixation can engender spatially congruent lateral shifts of attention, ie, leftward for small numbers and rightward for large ones, ie, the Att-SNARC effect. Finally, we summarize four experiments that tested whether the Att-SNARC depends on an active rather than passive processing of centrally presented digit cues. In line with other recent studies, these experiment do not replicate the original Att-SNARC and show that the mere perception of Arabic numerals does not trigger automatic shifts of attention. These shifts are instead found when the task requires the explicit left/right spatial coding of digit cues, ie, Spatial Att-SNARC (Fattorini et al., 2015b). Nonetheless, the reliability of the Spatial Att-SNARC effect seems not as strong as that of conventional SNARC effects where left/right codes are mapped onto responses rather than directly mapped on digit cues. Comparing the magnitude of digits to a numerical reference, ie, "5," also produced a Magnitude Comparison Att-SNARC that was weaker than the spatial one. However, the reliability of this Magnitude Comparison Att-SNARC should be considered with caution because, like in a study by Zanolie and Pecher (2014), we recently failed to replicate this effect in a separate behavioral-event-related potentials study in preparation (Fattorini et al., 2015a). All together the results from the present series of experiments support the hypothesis that spatial coding is not an intrinsic part of number representation and that number-space interaction is determined by the use of stimulus- or response-related spatial codes in the task at hand. © 2016 Elsevier B.V. All rights reserved.

Effects of Acute and Chronic Treatments with Dopamine D2 and D3 Receptor Ligands on Cocaine versus Food Choice in Rats.

PubMed

Thomsen, Morgane; Barrett, Andrew C; Butler, Paul; Negus, S Stevens; Caine, S Barak

2017-07-01

Dopamine D 3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, nondrug reinforcer. This study compared acute and chronic effects of dopamine D 2 - and D 3 -preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice. Acutely, the D 2 agonist R -(-)-norpropylapomorphine (NPA) and antagonist L-741,626 [3-[[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1 H -indole] produced leftward and rightward shifts in cocaine dose-effect curves, respectively, whereas the partial agonist terguride had no effect. All three drugs dose-dependently decreased food-maintained responding. Chronically, the effects of R -(-)-norpropylapomorphine and L-741,626 on cocaine self-administration showed marked tolerance, whereas suppression of food-reinforced behavior persisted. Acute effects of the D 3 ligands were less systematic and most consistent with nonselective decreases in cocaine- and food-maintained responding. Chronically, the D 3 agonist PF-592,379 [5-[(2 R ,5 S )-5-methyl-4-propylmorpholin-2-yl]pyridin-2-amine] increased cocaine choice, whereas an intermediate dose of the D 3 antagonist PG01037 [ N -[( E )-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-pyridin-2-ylbenzamide] produced a therapeutically desirable decrease in cocaine choice early in treatment; however, tolerance to this effect developed, and lower and higher doses were ineffective. D 3 ligands failed to significantly modify total cocaine intake but caused persistent decreases in food intake. Thus, D 2 -and D 3 -preferring ligands showed distinct profiles, consistent with different pharmacological actions. In addition, these results highlight the role of acute versus chronic treatment as a determinant of test drug effects. With the possible exception of the D 3 antagonist PG01037, no ligand was promising in terms of cocaine addiction treatment. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral septal neurones in vitro.

PubMed

Van den Hooff, P; Galvan, M

1992-08-01

1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM) to block any indirect effects, bath application of 5-HT (0.3-30 microM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1 receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization.7. It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.

The discriminative stimulus effects of i.v. nicotine in rhesus monkeys: Pharmacokinetics and apparent pA2 analysis with dihydro-β-erythroidine.

PubMed

Moerke, Megan J; Zhu, Andy Z X; Tyndale, Rachel F; Javors, Martin A; McMahon, Lance R

2017-04-01

Quantitative analysis of antagonism is infrequently used to identify nAChRs mediating behavioral effects. Here, nicotine (0.032 mg/kg i.v.) was established as a discriminative stimulus in rhesus monkeys responding under a fixed ratio 5 schedule; pharmacokinetics and underlying nAChR mechanism(s) were examined. When measured up to 4 h in venous blood, the training dose resulted in the following mean pharmacokinetic parameters: nicotine C max  = 71.7 ng/ml, t 1/2  = 116 min, and clearance = 6.25 ml/min/kg; cotinine C max  = 191 ng/ml; and 3OH-cotinine C max  = 63 ng/ml. The ED 50 value of nicotine to produce discriminative stimulus effects was 0.013 mg/kg. Epibatidine and varenicline increased drug-lever responding to 97% and 95%, respectively (ED 50 values = 0.00015 and 0.031 mg/kg, respectively), whereas cocaine, midazolam, and morphine produced no more than 28% drug-appropriate responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose-dependently attenuated the discriminative stimulus effects of the nicotine training dose, whereas methyllycaconitine (MLA) did not. DHβE (0.1 and 0.32) produced rightward shifts of the nicotine and varenicline dose-response functions; Schild plots fitted through individual data resulted in slopes that were not different from unity; the apparent pA 2 calculated for DHβE did not significantly differ in the presence of nicotine (6.58) or varenicline (6.45). Compared to human cigarette smoking, nicotine blood levels after 0.032 mg/kg nicotine i.v. took a similar time to reach maximal concentration, levels at Cmax were similar to smoking 2-3 cigarettes, while average nicotine levels were comparable to smoking 5-6 cigarettes. Apparent pA 2 analysis with DHβE under these conditions is consistent with nicotine and varenicline acting through the same nAChRs to produce discriminative stimulus effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dependence of endotoxin-induced vascular hyporeactivity on extracellular L-arginine.

PubMed

Schott, C A; Gray, G A; Stoclet, J C

1993-01-01

1. The dependence on extracellular L-arginine of vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) was studied in vivo in rats infused with LPS and in vitro in endothelium-denuded rat thoracic aortic rings exposed to LPS. 2. Infusion of LPS during 50 min at a dose of 10 mg kg-1 h-1 produced a significant impairment of the pressor effect of noradrenaline, while in tissues collected 60 min after the start of LPS infusion, no significant alteration in either plasma arginine concentration or aortic arginine content was found compared to saline-infused controls (where plasma arginine was 78.5 +/- 7 microM and aortic arginine 394 +/- 124 nmol g-1 tissue). 3. Incubation of isolated, endothelium-denuded aortic rings with LPS (10 micrograms ml-1) in the absence of L-arginine for 4 h at 37 degrees C produced a 6 fold (P < 0.01) rightward shift in the noradrenaline concentration-effect curve compared to polymyxin B (1 micrograms ml-1, a LPS neutralizing agent) and reduced by 15% the maximum observed tension. 4. The presence of L-arginine (100 microM) during the incubation with LPS and throughout the following contraction experiments caused a 15 fold (P < 0.01) increase in the EC50 of noradrenaline and greater depression (45%) of the maximum observed tension compared to polymyxin B-treated controls. Responses in control, non LPS-treated rings were unaffected by the presence of L-arginine. 5. The addition of L-arginine to rings incubated with LPS in the absence of L-arginine and maximally precontracted with noradrenaline (10 microM) induced a dose-dependent relaxation. The EC50 of L-arginine was 8.0+/-0.3mu.6. The reactivity of LPS-treated rings to noradrenaline both in the absence and presence of L-arginine was restored to control levels by N0-nitro-L-arginine methyl ester (L-NAME, 300 mu), an inhibitor of NO production and by methylene blue (3 JAM), an inhibitor of guanylate cyclase.7. Incubation of isolated aortae in the absence of L-arginine did not significantly decrease the tissue arginine content, whether LPS (10 fg ml-') was present or not. Similarly, the presence of L-arginine(100 mu) in the incubation medium did not modify the tissue arginine content.8. These results show that the LPS-induced impairment of vasoconstriction elicited by noradrenaline is dependent on extracellular L-arginine, although the tissue arginine content is not depleted after LPS pretreatment, and that circulating L-arginine is sufficient to activate maximally the vascular L-arginine/NO pathway in endotoxaemic rats.

Sequence analysis of Epstein-Barr virus (EBV) early genes BARF1 and BHRF1 in NK/T cell lymphoma from Northern China.

PubMed

Sun, Lingling; Che, Kui; Zhao, Zhenzhen; Liu, Song; Xing, Xiaoming; Luo, Bing

2015-09-04

NK/T cell lymphoma is an aggressive lymphoma almost always associated with EBV. BamHI-A rightward open reading frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) are two EBV early genes, which may be involved in the oncogenicity of EBV. It has been found that V29A strains, a BARF1 mutant subtype, showed higher prevalence in NPC, which may suggest the association between this variation and nasopharyngeal carcinoma (NPC). To characterize the sequence variation patterns of the Epstein-Barr virus (EBV) early genes and to elucidate their association with NK/T cell lymphoma, we analyzed the sequences of BARF1 and BHRF1 in EBV-positive NK/T cell lymphoma samples from Northern China. In situ hybridization (ISH) performed for EBV-encoded small RNA1 (EBER1) with specific digoxigenin-labeled probes was used to select the EBV positive lymphoma samples. Nested-polymerase chain reaction (nested-PCR) and DNA sequence analysis technique were used to obtain the sequences of BARF1 and BHRF1. The polymorphisms of these two genes were classified according to the signature changes and compared with the known corresponding EBV gene variation data. Two major subtypes of BARF1 gene, designated as B95-8 and V29A subtype, were identified. B95-8 subtype was the dominant subtype. The V29A subtype had one consistent amino acid change at amino acid residue 29 (V → A). Compared with B95-8, AA change at 88 (L → V) of BHRF1 was found in the majority of the isolates, and AA79 (V → L) mutation in a few isolates. Functional domains of BARF1 and BHRF1 were highly conserved. The distributions of BARF1 and BHRF1 subtypes had no significant differences among different EBV-associated malignancies and healthy donors. The sequences of BARF1 and BHRF1 are highly conserved which may contribute to maintain the biological function of these two genes. There is no evidence that particular EBV substrains of BARF1 or BHRF1 is region-restricted or disease-specific.

[The productivity of female shift workers].

PubMed

Vidacek, S; Radosević-Vidacek, B; Kaliterna, L; Prizmić, Z

1990-12-01

The productivity of female shift workers, working on a weekly rotating three-shift system, was examined. The afternoon shift was found to be the most productive and the night shift the least productive one. The greatest difference in productivity between shifts was found in the first two days of the week, when the productivity on night shift was significantly lower than that on the other two shifts. From the third day on there were no longer significant differences in productivity between shifts. The most productive and the least productive workers on night shift did not significantly differ in extraversion or in sleep duration after the night shift. Family responsibility was found to be associated with the duration of sleep after the night shift: married women slept significantly shorter after the night shift than unmarried women. However, this difference in sleep duration was not associated with productivity on night shift. Sleep duration after the afternoon shift (8 hours 40 minutes) was on average two hours longer than after the other two shifts. The difference in sleep duration after different shifts, along with circadian variations in alertness, readiness for work and performance efficiency, could be responsible for differences in productivity between shifts.

Procedure Selection and Patient Positioning Influence Spine Kinematics During High-Velocity, Low-Amplitude Spinal Manipulation Applied to the Low Back.

PubMed

Bell, Spencer; D'Angelo, Kevin; Kawchuk, Gregory N; Triano, John J; Howarth, Samuel J

This investigation compared indirect 3-dimensional angular kinematics (position, velocity, and acceleration) of the lumbar spine for 2 different high-velocity, low-amplitude (HVLA) spinal manipulation procedures (lumbar spinous pull or push), and altered initial patient lower limb posture. Twenty-four participants underwent 6 HVLA procedures directed toward the presumed L4 vertebra, reflecting each combination of 2 variants of a spinal manipulation application technique (spinous pull and push) and 3 initial hip flexion angles (0°, 45°, and 90°) applied using a right lateral recumbent patient position. All contact forces and moments between the patient and the external environment, as well as 3-dimensional kinematics of the patient's pelvis and thorax, were recorded. Lumbar spine angular positions, velocities, and accelerations were analyzed within the preload and impulse stages of each HVLA trial. Lumbar spine left axial rotation was greater for the pull HVLA. The pull HVLA also generated a greater maximum (leftward) and lower minimum (rightward) axial rotation velocity and deceleration and greater leftward and rightward lateral bend velocities, acceleration, and deceleration components. Not flexing the hip produced the greatest amount of extension, as well as the lowest axial rotation and maximum axial rotation acceleration during the impulse. This investigation provides basic kinematic information for clinicians to understand the similarities and differences between 2 HVLA side-lying manipulations in the lumbar spine. Use of these findings and novel technology can drive future research initiatives that can both affect clinical decision making and influence teaching environments surrounding spinal manipulative therapy skill acquisition. Copyright © 2017. Published by Elsevier Inc.

Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis.

PubMed

Zhou, Chen; Xie, Zhengde; Gao, Liwei; Liu, Chunyan; Ai, Junhong; Zhang, Li; Shen, Kunling

2015-10-01

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening complication of EBV infection. MicroRNAs (miRNAs) were small non-coding RNA, and EBV could encode miRNAs that are involved in the progression of infection. However, the profiles of EBV-miRNAs in EBV-HLH were unknown. Here, we aimed to profile the expression of EBV-miRNAs in children with EBV-HLH by analyzing 44 known EBV-miRNAs, encoded within the BamHI fragment H rightward open reading frame 1 (BHRF1) and the BamHI-A region rightward transcript (BART), in plasma and cellular targets by real-time quantitative PCR. The study included 15 children with EBV-HLH, 15 children with infectious mononucleosis (IM), and 15 healthy controls. CD8(+) T cells were found to be the cellular target of EBV infection in EBV-HLH, while CD19(+) B cells were infected with EBV in IM. We also found the greater levels of several miRNAs encoded by BART in EBV-HLH, compared to those in IM and healthy controls, whereas the levels of BHRF1 miRNAs were lower than those in IM. The profile and pattern of EBV-miRNAs in EBV-HLH indicated that EBV could display type II latency in EBV-HLH. Importantly, the level of plasma miR-BART16-1 continued decreasing during the whole chemotherapy, suggesting that plasma miR-BART16-1 could be a potential biomarker for monitoring EBV-HLH progression. The pathogenesis of EBV-HLH might be attributed to the abundance of EBV-miRNAs in EBV-HLH. These findings help elucidate the roles of EBV miRNAs in EBV-HLH, enabling the understanding of the basis of this disease and providing clues for its treatment.

Composite body movements modulate numerical cognition: evidence from the motion-numerical compatibility effect

PubMed Central

Cheng, Xiaorong; Ge, Hui; Andoni, Deljfina; Ding, Xianfeng; Fan, Zhao

2015-01-01

A recent hierarchical model of numerical processing, initiated by Fischer and Brugger (2011) and Fischer (2012), suggested that situated factors, such as different body postures and body movements, can influence the magnitude representation and bias numerical processing. Indeed, Loetscher et al. (2008) found that participants’ behavior in a random number generation task was biased by head rotations. More small numbers were reported after leftward than rightward head turns, i.e., a motion-numerical compatibility effect. Here, by carrying out two experiments, we explored whether similar motion-numerical compatibility effects exist for movements of other important body components, e.g., arms, and for composite body movements as well, which are basis for complex human activities in many ecologically meaningful situations. In Experiment 1, a motion-numerical compatibility effect was observed for lateral rotations of two body components, i.e., the head and arms. Relatively large numbers were reported after making rightward compared to leftward movements for both lateral head and arm turns. The motion-numerical compatibility effect was observed again in Experiment 2 when participants were asked to perform composite body movements of congruent movement directions, e.g., simultaneous head left turns and arm left turns. However, it disappeared when the movement directions were incongruent, e.g., simultaneous head left turns and arm right turns. Taken together, our results extended Loetscher et al.’s (2008) finding by demonstrating that their effect is effector-general and exists for arm movements. Moreover, our study reveals for the first time that the impact of spatial information on numerical processing induced by each of the two sensorimotor-based situated factors, e.g., a lateral head turn and a lateral arm turn, can cancel each other out. PMID:26594188

Low is large: spatial location and pitch interact in voice-based body size estimation.

PubMed

Pisanski, Katarzyna; Isenstein, Sari G E; Montano, Kelyn J; O'Connor, Jillian J M; Feinberg, David R

2017-05-01

The binding of incongruent cues poses a challenge for multimodal perception. Indeed, although taller objects emit sounds from higher elevations, low-pitched sounds are perceptually mapped both to large size and to low elevation. In the present study, we examined how these incongruent vertical spatial cues (up is more) and pitch cues (low is large) to size interact, and whether similar biases influence size perception along the horizontal axis. In Experiment 1, we measured listeners' voice-based judgments of human body size using pitch-manipulated voices projected from a high versus a low, and a right versus a left, spatial location. Listeners associated low spatial locations with largeness for lowered-pitch but not for raised-pitch voices, demonstrating that pitch overrode vertical-elevation cues. Listeners associated rightward spatial locations with largeness, regardless of voice pitch. In Experiment 2, listeners performed the task while sitting or standing, allowing us to examine self-referential cues to elevation in size estimation. Listeners associated vertically low and rightward spatial cues with largeness more for lowered- than for raised-pitch voices. These correspondences were robust to sex (of both the voice and the listener) and head elevation (standing or sitting); however, horizontal correspondences were amplified when participants stood. Moreover, when participants were standing, their judgments of how much larger men's voices sounded than women's increased when the voices were projected from the low speaker. Our results provide novel evidence for a multidimensional spatial mapping of pitch that is generalizable to human voices and that affects performance in an indirect, ecologically relevant spatial task (body size estimation). These findings suggest that crossmodal pitch correspondences evoke both low-level and higher-level cognitive processes.

Cortical thickness abnormalities associated with dyslexia, independent of remediation status.

PubMed

Ma, Yizhou; Koyama, Maki S; Milham, Michael P; Castellanos, F Xavier; Quinn, Brian T; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

2015-01-01

Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the "reading network." Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same "double hit" of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status.

Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes.

PubMed

Savic, Ivanka

2014-01-01

Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47,XXY). Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis. All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46,XY males than 46,XX females and 47,XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46,XX females and 47,XXY males, but were not related to sex hormone levels. No asymmetry differences between 46,XX females and 47,XXY males, and no overall effects of brain size were detected. The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner.

Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes

PubMed Central

Savic, Ivanka

2014-01-01

Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47,XXY). Methods: Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis. Results: All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46,XY males than 46,XX females and 47,XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46,XX females and 47,XXY males, but were not related to sex hormone levels. No asymmetry differences between 46,XX females and 47,XXY males, and no overall effects of brain size were detected. Conclusion: The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner. PMID:25505869

Cortical thickness abnormalities associated with dyslexia, independent of remediation status

PubMed Central

Ma, Yizhou; Koyama, Maki S.; Milham, Michael P.; Castellanos, F. Xavier; Quinn, Brian T.; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

2014-01-01

Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the “reading network.” Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same “double hit” of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status. PMID:25610779

Distinct frontal regions subserve evaluation of linguistic and emotional aspects of speech intonation.

PubMed

Wildgruber, D; Hertrich, I; Riecker, A; Erb, M; Anders, S; Grodd, W; Ackermann, H

2004-12-01

In addition to the propositional content of verbal utterances, significant linguistic and emotional information is conveyed by the tone of speech. To differentiate brain regions subserving processing of linguistic and affective aspects of intonation, discrimination of sentences differing in linguistic accentuation and emotional expressiveness was evaluated by functional magnetic resonance imaging. Both tasks yielded rightward lateralization of hemodynamic responses at the level of the dorsolateral frontal cortex as well as bilateral thalamic and temporal activation. Processing of linguistic and affective intonation, thus, seems to be supported by overlapping neural networks comprising partially right-sided brain regions. Comparison of hemodynamic activation during the two different tasks, however, revealed bilateral orbito-frontal responses restricted to the affective condition as opposed to activation of the left lateral inferior frontal gyrus confined to evaluation of linguistic intonation. These findings indicate that distinct frontal regions contribute to higher level processing of intonational information depending on its communicational function. In line with other components of language processing, discrimination of linguistic accentuation seems to be lateralized to the left inferior-lateral frontal region whereas bilateral orbito-frontal areas subserve evaluation of emotional expressiveness.

Periodic alternating nystagmus during caloric stimulation.

PubMed

Taki, Masakatsu; Hasegawa, Tatsuhisa; Adachi, Naoko; Fujita, Tomoki; Sakaguchi, Hirofumi; Hisa, Yasuo

2014-04-01

Periodic alternating nystagmus (PAN) is a form of horizontal jerk nystagmus characterized by periodic reversals in direction. We report a case who exhibited transient PAN induced by caloric stimulation. The patient was a 75-year-old male. He had experienced floating sensation in January 2010. Eight months later, he was referred to our university hospital. Gaze nystagmus and positional tests revealed no nystagmus. Only weak right-beating horizontal nystagmus was observed during left Dix-Hallpike maneuver. Electronystagmography showed normal saccadic and smooth pursuit eye movements. The optokinetic nystagmus pattern test was also bilaterally normal. However, during the caloric stimulation to the right ear, at 166 s from the start of irrigation, the direction of nystagmus alternated from leftward to rightward, and thereafter this reversal of direction repeated 15 times. Magnetic resonance imaging showed no significant lesion except for chronic ischemia in the brain. The patient probably had some kind of latent lesion of impaired velocity storage and exhibited transient PAN induced by caloric stimulation. Caloric stimulation is useful and simple examination to disclose latent eye movement disorders of which velocity storage mechanism is impaired. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Hemispheric asymmetry of electroencephalography-based functional brain networks.

PubMed

Jalili, Mahdi

2014-11-12

Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.

Sex dependence of brain size and shape in bipolar disorder: an exploratory study.

PubMed

Mackay, Clare E; Roddick, Elina; Barrick, Thomas R; Lloyd, Adrian J; Roberts, Neil; Crow, Tim J; Young, Allan H; Ferrier, I Nicol

2010-05-01

Anomalies of asymmetry and sex differences in brain structure have frequently been described in schizophrenic illnesses but have seldom been explored in bipolar disorder. We measured volumes of the left and right frontal, temporal, parietal, and occipital lobes and computed the magnitude of brain torque (i.e., rightward frontal and leftward occipital asymmetry) for 49 patients with bipolar disorder and 47 healthy controls and performed an exploratory analysis of sex differences in patients and controls. Patients had significantly greater cerebrospinal fluid volume than controls, but no difference in total brain volume. There were no main effects of diagnosis in gray matter lobe volume or brain torque, but when analyses were performed separately for male and female subjects, significant sex-by-diagnosis interactions were found in the volume of the left frontal, left temporal, right parietal, and right occipital lobes, such that male patients with bipolar disorder tend toward larger, more symmetric brains than male controls, whereas female patients tend toward smaller, more asymmetric brains than female controls. The lateralised nature of these interactions was such that the normal sex difference in volume was significantly accentuated, whilst the normal sex difference in asymmetry tended to be diminished in patients with bipolar disorder. We conclude that bipolar disorder in part reflects an interaction between brain growth and sex along the anterior-posterior axis of the human brain.

Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats.

PubMed

Hajnal, Andras; Kovacs, Peter; Ahmed, Tamer; Meirelles, Katia; Lynch, Christopher J; Cooney, Robert N

2010-10-01

Roux-en-Y gastric bypass surgery (GBS) is the most effective treatment for morbid obesity. GBS is a restrictive malabsorptive procedure, but many patients also report altered taste preferences. This study investigated the effects of GBS or a sham operation (SH) on body weight, glucose tolerance, and behavioral and neuronal taste functions in the obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-1 receptors and lean controls (LETO). OLETF-GBS rats lost body weight (-26%) and demonstrated improved glucose tolerance. They also expressed a reduction in 24-h two-bottle preference for sucrose (0.3 and 1.0 M) and decreased 10-s lick responses for sucrose (0.3 through 1.5 M) compared with OLETF-SH or LETO-GBS. A similar effect was noted for other sweet compounds but not for salty, sour, or bitter tastants. In lean rats, GBS did not alter responses to any stimulus tested. Extracellular recordings from 170 taste-responsive neurons of the pontine parabrachial nucleus revealed a rightward shift in concentration responses to oral sucrose in obese compared with lean rats (OLETF-SH vs. LETO-SH): overall increased response magnitudes (above 0.9 M), and maximum responses occurring at higher concentrations (+0.46 M). These effects were reversed by GBS, and neural responses in OLETF-GBS were statistically not different from those in any LETO groups. These findings confirm obesity-related alterations in taste functions and demonstrate the ability of GBS to alleviate these impairments. Furthermore, the beneficial effects of GBS appear to be independent of CCK-1 receptor signaling. An understanding of the underlying mechanisms for reduced preferences for sweet taste could help in developing less invasive treatments for obesity.

Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

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

Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

1988-07-12

The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no suchmore » effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.« less

Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders.

PubMed

Mehmood, Malik Hassan; Gilani, Anwarul Hassan

2010-10-01

Dried fruits of Piper nigrum (black pepper) are commonly used in gastrointestinal disorders. The aim of this study was to rationalize the medicinal use of pepper and its principal alkaloid, piperine, in constipation and diarrhea using in vitro and in vivo assays. When tested in isolated guinea pig ileum, the crude extract of pepper (Pn.Cr) (1–10 mg/mL) and piperine (3–300 μM) caused a concentration-dependent and atropine-sensitive stimulant effect. In rabbit jejunum, Pn.Cr (0.01–3.0 mg/mL) and piperine (30–1,000 μM) relaxed spontaneous contractions, similar to loperamide and nifedipine. The relaxant effect of Pn.Cr and piperine was partially inhibited in the presence of naloxone (1 μM) similar to that of loperamide, suggesting the naloxone-sensitive effect in addition to the Ca(2+) channel blocking (CCB)-like activity, which was evident by its relaxant effect on K+ (80 mM)-induced contractions. The CCB activity was confirmed when pretreatment of the tissue with Pn.Cr (0.03–0.3 mg/mL) or piperine (10–100 μM) caused a rightward shift in the concentration–response curves of Ca(2+), similar to loperamide and nifedipine. In mice, Pn.Cr and piperine exhibited a partially atropine-sensitive laxative effect at lower doses, whereas at higher doses it caused antisecretory and antidiarrheal activities that were partially inhibited in mice pretreated with naloxone (1.5 mg/kg), similar to loperamide. This study illustrates the presence of spasmodic (cholinergic) and antispasmodic (opioid agonist and Ca(2+) antagonist) effects, thus providing the possible explanation for the medicinal use of pepper and piperine in gastrointestinal motility disorders.

New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models

PubMed Central

O’Brien, William G.; Ling, Han Shawn; Lee, Cheng Chi

2017-01-01

The observation that induced torpor in non-hibernating mammals could result from an increased AMP concentration in circulation led our investigation to reveal that the added AMP altered oxygen transport of erythrocytes. To further study the effect of AMP in regulation of erythrocyte function and systemic metabolism, we generated mouse models deficient in key erythrocyte enzymes in AMP metabolism. We have previously reported altered erythrocyte adenine nucleotide levels corresponding to altered oxygen saturation in mice deficient in both CD73 and AMPD3. Here we further investigate how these Ampd3-/-/Cd73-/- mice respond to the administered dose of AMP in comparison with the control models of single enzyme deficiency and wild type. We found that Ampd3-/-/Cd73-/- mice are more sensitive to AMP-induced hypometabolism than mice with a single enzyme deficiency, which are more sensitive than wild type. A dose-dependent rightward shift of erythrocyte p50 values in response to increasing amounts of extracellular AMP was observed. We provide further evidence for the direct uptake of AMP by erythrocytes that is insensitive to dipyridamole, a blocker for ENT1. The uptake of AMP by the erythrocytes remained linear at the highest concentration tested, 10mM. We also observed competitive inhibition of AMP uptake by ATP and ADP but not by the other nucleotides and metabolites tested. Importantly, our studies suggest that AMP uptake is associated with an erythrocyte ATP release that is partially sensitive to inhibition by TRO19622 and Ca++ ion. Taken together, our study suggests a novel mechanism by which erythrocytes recycle and maintain their adenine nucleotide pool through AMP uptake and ATP release. PMID:28746349

New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models.

PubMed

O'Brien, William G; Ling, Han Shawn; Zhao, Zhaoyang; Lee, Cheng Chi

2017-01-01

The observation that induced torpor in non-hibernating mammals could result from an increased AMP concentration in circulation led our investigation to reveal that the added AMP altered oxygen transport of erythrocytes. To further study the effect of AMP in regulation of erythrocyte function and systemic metabolism, we generated mouse models deficient in key erythrocyte enzymes in AMP metabolism. We have previously reported altered erythrocyte adenine nucleotide levels corresponding to altered oxygen saturation in mice deficient in both CD73 and AMPD3. Here we further investigate how these Ampd3-/-/Cd73-/- mice respond to the administered dose of AMP in comparison with the control models of single enzyme deficiency and wild type. We found that Ampd3-/-/Cd73-/- mice are more sensitive to AMP-induced hypometabolism than mice with a single enzyme deficiency, which are more sensitive than wild type. A dose-dependent rightward shift of erythrocyte p50 values in response to increasing amounts of extracellular AMP was observed. We provide further evidence for the direct uptake of AMP by erythrocytes that is insensitive to dipyridamole, a blocker for ENT1. The uptake of AMP by the erythrocytes remained linear at the highest concentration tested, 10mM. We also observed competitive inhibition of AMP uptake by ATP and ADP but not by the other nucleotides and metabolites tested. Importantly, our studies suggest that AMP uptake is associated with an erythrocyte ATP release that is partially sensitive to inhibition by TRO19622 and Ca++ ion. Taken together, our study suggests a novel mechanism by which erythrocytes recycle and maintain their adenine nucleotide pool through AMP uptake and ATP release.

Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi.

PubMed

Santicioli, Paolo; Meini, Stefania; Giuliani, Sandro; Lecci, Alessandro; Maggi, Carlo Alberto

2013-10-24

In this study we have characterized the pharmacological profile of the non-peptide tachykinin NK 2 receptor antagonist ibodutant (MEN15596) in guinea pig isolated main bronchi contractility. The antagonist potency of ibodutant was evaluated using the selective NK 2 receptor agonist [βAla 8 ]NKA(4-10)-mediated contractions of guinea pig isolated main bronchi. In this assay ibodutant (30, 100 and 300nM) induced a concentration-dependent rightward shift of the [βAla 8 ]NKA(4-10) concentration-response curves without affecting the maximal contractile effect. The analysis of the results yielded a Schild-plot linear regression with a slope not different from unity (0.95, 95% c.l. 0.65-1.25), thus indicating a surmountable behaviour. The calculated apparent antagonist potency as pK B value was 8.31±0.05. Ibodutant (0.3-100nM), produced a concentration-dependent inhibition of the nonadrenergic-noncholinergic (NANC) contractile response induced by electrical field stimulation (EFS) of intrinsic airway nerves in guinea pig isolated main bronchi. At the highest concentration tested (100nM) ibodutant almost abolished the EFS-induced bronchoconstriction (95±4% inhibition), the calculated IC 50 value was 2.98nM (95% c.l. 1.73-5.16nM). In bronchi from ovalbumin (OVA) sensitized guinea pigs ibodutant (100nM) did not affect the maximal contractile response to OVA, but completely prevented the slowing in the fading of the motor response induced by phosphoramidon pretreatment linked to the endogenous neurokinin A release. Altogether, the present study demonstrate that ibodutant is a potent NK 2 receptor antagonist in guinea pig airways. © 2013 Published by Elsevier B.V.

Can more than one incremental cycling test be performed within one day?

PubMed

Scharhag-Rosenberger, Friederike; Carlsohn, Anja; Lundby, Carsten; Schüler, Stefan; Mayer, Frank; Scharhag, Jürgen

2014-01-01

Changes in performance parameters over four consecutive maximal incremental cycling tests were investigated to determine how many tests can be performed within one single day without negatively affecting performance. Sixteen male and female subjects (eight trained (T): 25 ± 3 yr, BMI 22.6 ± 2.5 kg·m(-2), maximal power output (P(max)) 4.6 ± 0.5 W·kg(-1); eight untrained (UT): 27 ± 3 yr, BMI 22.3 ± 1.2 kg·m(-2), P(max) 2.9 ± 0.3 W·kg(-1)) performed four successive maximal incremental cycling tests separated by 1.5 h of passive rest. Individual energy requirements were covered by standardised meals between trials. Maximal oxygen uptake (VO(2max)) remained unchanged over the four tests in both groups (P = 0.20 and P = 0.33, respectively). P(max) did not change in the T group (P = 0.32), but decreased from the third test in the UT group (P < 0.01). Heart rate responses to submaximal exercise were elevated from the third test in the T group and from the second test in the UT group (P < 0.05). The increase in blood lactate shifted rightward over the four tests in both groups (P < 0.001 and P < 0.01, respectively). Exercise-induced net increases in epinephrine and norepinephrine were not different between the tests in either group (P ≥ 0.15). If VO(2max) is the main parameter of interest, trained and untrained individuals can perform at least four maximal incremental cycling tests per day. However, because other parameters changed after the first and second test, respectively, no more than one test per day should be performed if parameters other than VO(2max) are the prime focus.

Effect of melatonin on the blood oxygen transport during hypothermia and rewarming in rats.

PubMed

Hlutkin, S; Zinchuk, V

2008-01-01

We aimed to study effect of melatonin on the blood oxygen transport during hypothermia and rewarming in rats. Cold exposure was performed on male rats (body weight 220-270 g, n=48) for 120 minutes under the box water temperature of 19 degrees C; rewarming took the next 120 min, with a mean rate of 0.06 degrees C/min. Melatonin was administered intraperitoneally 30 min before the cold exposure (bolus doses of 0.1, 1 or 10 mg/kg, or 1 mg/kg*day for 4 days). Haemoglobin-oxygen affinity was evaluated by p50 (blood pO2 at its 50% O2 saturation) determined by the "mixing" method at 37 degrees C, pH 7.4 and pCO2 40 mm Hg (p50stand) and at actual pH, pCO2 and temperature (p50act). After hypothermia and rewarming, the values of p50stand and p50act were 31.5+/-0.28 and 30.2+/-0.61 mm Hg, respectively. The 0.1 mg/kg of melatonin virtually did not change these values, whereas the larger doses increased them. This effect was maximal after the prolonged (4 days) melatonin administration: p50stand rose by 5.4% (p<0.05) and p50act--by 12.9 (p<0.05) compared with rats without the melatonin treatment. Melatonin affected the mechanisms of O2 transport by decreasing the haemoglobin-oxygen affinity (shifting the oxygen dissociation curve of haemoglobin rightwards) and promoting the tissue oxygenation, thereby enhancing the body's resistance to cold. The melatonin effect mediated by haemoglobin-oxygen affinity change may be used for the correction of metabolic disorders and the improvement of the body's resistance to low environmental temperature.

Effect of GABA agonists and GABA-A receptor modulators on cocaine- and food-maintained responding and cocaine discrimination in rats.

PubMed

Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak

2005-11-01

Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.

Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents

PubMed Central

Fantegrossi, William E.; Reissig, Chad J.; Katz, Elyse B.; Yarosh, Haley L.; Rice, Kenner C.; Winter, Jerrold C.

2008-01-01

N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptamine (psilocybin), or 3,4-methylenedioxymethamphetamine (MDMA). A separate group of rats was also trained to recognize DPT itself as a discriminative stimulus, and in all cases, the behavioral effects of DPT were challenged with the selective serotonin (5-HT)2A antagonist M100907, the 5-HT1A selective antagonist WAY-100635, or their combination. In the head twitch assay, DPT elicited dose-dependent effects, producing a biphasic dose-effect curve. WAY-100635 produced a parallel rightward shift in the dose-effect curve for head twitches, indicative of surmountable antagonism, but the antagonist effects of M100907 were functionally insurmountable. DPT produced partial to full substitution when tested in rats trained to discriminate LSD, psilocybin or MDMA, and served as a discriminative stimulus. In all cases, the antagonist effects of M100907 were more profound than were those of WAY-100635. DPT is thus active in two rodent models relevant to 5-HT2 agonist activity. The effectiveness with which M100907 antagonizes the behavioral actions of this compound strongly suggests that the 5-HT2A receptor is an important site of action for DPT, but the modulatory actions of WAY-100635 also imply a 5-HT1A-mediated component to the actions of this compound. PMID:17905422

Pulmonary anti-inflammatory effects and spasmolytic properties of Costa Rican noni juice (Morinda citrifolia L.).

PubMed

Dussossoy, Emilie; Bichon, Florence; Bony, Emilie; Portet, Karine; Brat, Pierre; Vaillant, Fabrice; Michel, Alain; Poucheret, Patrick

2016-11-04

Morinda citrifolia L. (Noni) is a medicinal plant used in Polynesia for many properties such as anti-inflammatory, anti-diabetic and antineoplastic effects. Recent studies showed that noni juice have anti-oxidant and acute anti-inflammatory activities likely due to polyphenols, iridoids and vitamin C content. The present study was undertaken to evaluate chronic anti-inflammatory and spasmolytic effects of noni juice. Therefore, we evaluated the effect of oral or intraperitoneal administrations of noni juice in vivo on the lung inflammation in ovalbumin (OVA) sensitized Brown Norway rat (with prednisolone 10mg/kg intraperitoneously as reference compound) and the ex vivo effect of noni juice on BaCl 2 (calcium signal) or methacholine (cholinergic signal) induced spasms in jejunum segments. We found that noni juice (intraperitoneously 2.17mL/kg and orally 4.55mL/kg) reduced the inflammation in OVA-sensitized Brown Norway rat with regard to the decreased number of inflammatory cells in lung (macrophages minus 20-26%, lymphocytes minus 58-34%, eosinophils minus 53-30%, neutrophils minus 70-28% respectively). Noni juice demonstrated a dose-dependent NO scavenging effect up to 8.1nmol of nitrites for 50µL of noni juice. In addition noni juice inhibited (up to 90%) calcium and cholinergic induced spasms on the jejunum segments model with a rightward shift of the concentration response curve. We describe for the first time that noni juice demonstrate (1) a chronic anti-inflammatory activity on sensitized lungs along with (2) a spasmolytic effect integrating a calcium channel blocker activity component. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

PubMed

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

Fluorescent Protein-Based Ca2+ Sensor Reveals Global, Divalent Cation-Dependent Conformational Changes in Cardiac Troponin C.

PubMed

Badr, Myriam A; Pinto, Jose R; Davidson, Michael W; Chase, P Bryant

2016-01-01

Cardiac troponin C (cTnC) is a key effector in cardiac muscle excitation-contraction coupling as the Ca2+ sensing subunit responsible for controlling contraction. In this study, we generated several FRET sensors for divalent cations based on cTnC flanked by a donor fluorescent protein (CFP) and an acceptor fluorescent protein (YFP). The sensors report Ca2+ and Mg2+ binding, and relay global structural information about the structural relationship between cTnC's N- and C-domains. The sensors were first characterized using end point titrations to decipher the response to Ca2+ binding in the presence or absence of Mg2+. The sensor that exhibited the largest responses in end point titrations, CTV-TnC, (Cerulean, TnC, and Venus) was characterized more extensively. Most of the divalent cation-dependent FRET signal originates from the high affinity C-terminal EF hands. CTV-TnC reconstitutes into skinned fiber preparations indicating proper assembly of troponin complex, with only ~0.2 pCa unit rightward shift of Ca2+-sensitive force development compared to WT-cTnC. Affinity of CTV-TnC for divalent cations is in agreement with known values for WT-cTnC. Analytical ultracentrifugation indicates that CTV-TnC undergoes compaction as divalent cations bind. C-terminal sites induce ion-specific (Ca2+ versus Mg2+) conformational changes in cTnC. Our data also provide support for the presence of additional, non-EF-hand sites on cTnC for Mg2+ binding. In conclusion, we successfully generated a novel FRET-Ca2+ sensor based on full length cTnC with a variety of cellular applications. Our sensor reveals global structural information about cTnC upon divalent cation binding.

Cardiovascular and haematological responses of Atlantic cod (Gadus morhua) to acute temperature increase.

PubMed

Gollock, M J; Currie, S; Petersen, L H; Gamperl, A K

2006-08-01

For fish to survive large acute temperature increases (i.e. >10.0 degrees C) that may bring them close to their critical thermal maximum (CTM), oxygen uptake at the gills and distribution by the cardiovascular system must increase to match tissue oxygen demand. To examine the effects of an acute temperature increase ( approximately 1.7 degrees C h(-1) to CTM) on the cardiorespiratory physiology of Atlantic cod, we (1) carried out respirometry on 10.0 degrees C acclimated fish, while simultaneously measuring in vivo cardiac parameters using Transonic probes, and (2) constructed in vitro oxygen binding curves on whole blood from 7.0 degrees C acclimated cod at a range of temperatures. Both cardiac output (Q) and heart rate (fh) increased until near the fish's CTM (22.2+/-0.2 degrees C), and then declined rapidly. Q(10) values for Q and fh were 2.48 and 2.12, respectively, and increases in both parameters were tightly correlated with O(2) consumption. The haemoglobin (Hb)-oxygen binding curve at 24.0 degrees C showed pronounced downward and rightward shifts compared to 20.0 degrees C and 7.0 degrees C, indicating that both binding capacity and affinity decreased. Further, Hb levels were lower at 24.0 degrees C than at 20.0 degrees C and 7.0 degrees C. This was likely to be due to cell swelling, as electrophoresis of Hb samples did not suggest protein denaturation, and at 24.0 degrees C Hb samples showed peak absorbance at the expected wavelength (540 nm). Our results show that cardiac function is unlikely to limit metabolic rate in Atlantic cod from Newfoundland until close to their CTM, and we suggest that decreased blood oxygen binding capacity may contribute to the plateau in oxygen consumption.

Tolerance to the antinociceptive effect of morphine in the absence of short-term presynaptic desensitization in rat periaqueductal gray neurons.

PubMed

Fyfe, Leon W; Cleary, Daniel R; Macey, Tara A; Morgan, Michael M; Ingram, Susan L

2010-12-01

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D(50) = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin was decreased in morphine-tolerant (EC(50) = 708 nM) compared with saline-pretreated rats (EC(50) = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization.

Tolerance to the Antinociceptive Effect of Morphine in the Absence of Short-Term Presynaptic Desensitization in Rat Periaqueductal Gray Neurons

PubMed Central

Fyfe, Leon W.; Cleary, Daniel R.; Macey, Tara A.; Morgan, Michael M.

2010-01-01

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D50 = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin was decreased in morphine-tolerant (EC50 = 708 nM) compared with saline-pretreated rats (EC50 = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization. PMID:20739455

Combining new tools to assess renal function and morphology: a holistic approach to study the effects of aging and a congenital nephron deficit.

PubMed

Geraci, Stefania; Chacon-Caldera, Jorge; Cullen-McEwen, Luise; Schad, Lothar R; Sticht, Carsten; Puelles, Victor G; Bertram, John F; Gretz, Norbert

2017-09-01

Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life ( t 1/2 ) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes. Copyright © 2017 the American Physiological Society.

Activation of neurokinin NK(2) receptors by tachykinin peptides causes contraction of uterus in pregnant women near term.

PubMed

Patak, E N; Ziccone, S; Story, M E; Fleming, A J; Lilley, A; Pennefather, J N

2000-06-01

The aim of this study was firstly to elucidate whether the mammalian tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)-regulated contractility of myometrium obtained from near-term pregnant women, and secondly to investigate the receptor subtype(s) responsible. In the presence of peptidase inhibitors, i.e. thiorphan (3 micromol/l; endopeptidase 24.11 inhibitor), captopril (10 micromol/l; angiotensin converting enzyme inhibitor) and bestatin (10 micromol/l; aminopeptidase inhibitor); all three mammalian tachykinins elicited concentration-related contractions of isolated myometrial preparations. The rank order of agonist potency of the mammalian tachykinins in the presence of the peptidase inhibitors was NKA > SP = NKB, indicating that the contractile effects were mediated by activation of an NK(2) receptor. The NK(2) receptor-selective agonist, [Lys(5), MeLeu(9), Nle(10)]NKA(4-10), produced concentration-related contractile responses, while the respective NK(1) and NK(3) receptor-selective agonists, [Sar(9), Met(O(2))(11)]SP and [N-MePhe(7)]NKB, had no effect either in the absence or presence of the peptidase inhibitors. The NK(2) receptor-selective antagonist, SR48968, produced concentration-related rightward shift in the log concentration curve to [Lys(5), MeLeu(9), Nle(10)]NKA(4-10). This study shows that tachykinins elicit contractile effects on human myometrium obtained from pregnant women near term, and that these effects are mediated by an NK(2) receptor. An excitatory effect of the tachykinins on these preparations could indicate a physiological role for these peptides in enhancing contractility of the uterus in women at term.

The anti-inflammatory effects of PGE2 on human lung macrophages are mediated by the EP4 receptor.

PubMed

Gill, Sharonjit K; Yao, Yiwen; Kay, Linda J; Bewley, Martin A; Marriott, Helen M; Peachell, Peter T

2016-11-01

PGE 2 inhibits cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE 2 has not been defined. The aim of this study was to identify the EP receptor by which PGE 2 inhibits cytokine generation from human lung macrophages. This was determined by using recently developed EP receptor ligands. The effects of PGE 2 and EP-selective agonists on LPS-induced generation of TNF-α and IL-6 from macrophages were evaluated. The effects of EP 2 -selective (PF-04852946, PF-04418948) and EP 4 -selective (L-161,982, CJ-042794) receptor antagonists on PGE 2 responses were studied. The expression of EP receptor subtypes by human lung macrophages was determined by RT-PCR. PGE 2 inhibited LPS-induced and Streptococcus pneumoniae-induced cytokine generation from human lung macrophages. Analysis of mRNA levels indicated that macrophages expressed EP 2 and EP 4 receptors. L-902,688 (EP 4 receptor-selective agonist) was considerably more potent than butaprost (EP 2 receptor-selective agonist) as an inhibitor of TNF-α generation from macrophages. EP 2 receptor-selective antagonists had marginal effects on the PGE 2 inhibition of TNF-α generation, whereas EP 4 receptor-selective antagonists caused rightward shifts in the PGE 2 concentration-response curves. These studies demonstrate that the EP 4 receptor is the principal receptor that mediates the anti-inflammatory effects of PGE 2 on human lung macrophages. This suggests that EP 4 receptor agonists could be effective anti-inflammatory agents in human lung disease. © 2016 The British Pharmacological Society.

Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

PubMed Central

Maguire, David R; Gerak, Lisa R; France, Charles P

2015-01-01

Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

Non-linear effects of transcranial direct current stimulation as a function of individual baseline performance: Evidence from biparietal tDCS influence on lateralized attention bias.

PubMed

Benwell, Christopher S Y; Learmonth, Gemma; Miniussi, Carlo; Harvey, Monika; Thut, Gregor

2015-08-01

Transcranial direct current stimulation (tDCS) is a well-established technique for non-invasive brain stimulation (NIBS). However, the technique suffers from a high variability in outcome, some of which is likely explained by the state of the brain at tDCS-delivery but for which explanatory, mechanistic models are lacking. Here, we tested the effects of bi-parietal tDCS on perceptual line bisection as a function of tDCS current strength (1 mA vs 2 mA) and individual baseline discrimination sensitivity (a measure associated with intrinsic uncertainty/signal-to-noise balance). Our main findings were threefold. We replicated a previous finding (Giglia et al., 2011) of a rightward shift in subjective midpoint after Left anode/Right cathode tDCS over parietal cortex (sham-controlled). We found this effect to be weak over our entire sample (n = 38), but to be substantial in a subset of participants when they were split according to tDCS-intensity and baseline performance. This was due to a complex, nonlinear interaction between these two factors. Our data lend further support to the notion of state-dependency in NIBS which suggests outcome to depend on the endogenous balance between task-informative 'signal' and task-uninformative 'noise' at baseline. The results highlight the strong influence of individual differences and variations in experimental parameters on tDCS outcome, and the importance of fostering knowledge on the factors influencing tDCS outcome across cognitive domains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Microphysiometric analysis of human α1a-adrenoceptor expressed in Chinese hamster ovary cells

PubMed Central

Taniguchi, Takanobu; Inagaki, Rika; Murata, Satoshi; Akiba, Isamu; Muramatsu, Ikunobu

1999-01-01

The human recombinant α1a-adrenoceptor (AR) has been stably expressed in Chinese hamster ovary cells. Four stable clones, aH4, aH5, aH6 and aH7, expressing 30, 370, 940 and 2900 fmol AR mg−1 protein, respectively, have been employed to characterize this AR subtype using radioligand binding and microphysiometry to measure extracellular acidification rates.Noradrenaline (NA) gave concentration-dependent responses in microphysiometry with increasing extracellular acidification rates. The potency of NA increased as the receptor density increased; pEC50 values of NA for the clones aH4, aH5, aH6 and aH7 were 6.9, 7.5, 7.8 and 8.1, respectively. This increase of potency according to receptor density indicates the presence of spare receptor for NA. Methoxamine, phenylephrine, oxymetazoline and clonidine also gave concentration-dependent responses with various intrinsic activities.Antagonists shifted concentration-response curves for NA rightward in a concentration-dependent manner. Schild analysis revealed that the affinity profile of this AR subtype to antagonists in the clone aH7 had a typical pattern for the α1a-AR; high affinity for prazosin and WB 4101, and low affinity for BMY7378 (pA2=9.5, 9.8 and 7.3, respectively). This profile is similar in the case of the clone aH4. These affinities were in good agreement with those obtained in binding experiments.These results have demonstrated that (1) classical receptor theory can be applied in microphysiometry, and (2) microphysiometry is a useful tool to investigate the pharmacological characterization of α1a-AR. PMID:10433504

SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor

PubMed Central

Bradley, ME; Bond, ME; Manini, J; Brown, Z; Charlton, SJ

2009-01-01

Background and purpose: In several previous studies, the C-X-C chemokine receptor (CXCR)2 antagonist 1-(2-bromo-phenyl)-3-(7-cyano-3H-benzotriazol-4-yl)-urea (SB265610) has been described as binding competitively with the endogenous agonist. This is in contrast to many other chemokine receptor antagonists, where the mechanism of antagonism has been described as allosteric. Experimental approach: To determine whether it displays a unique mechanism among the chemokine receptor antagonists, the mode of action of SB265610 was investigated at the CXCR2 receptor using radioligand and [35S]-GTPγS binding approaches in addition to chemotaxis of human neutrophils. Key results: In equilibrium saturation binding studies, SB265610 depressed the maximal binding of [125I]-interleukin-8 ([125I]-IL-8) without affecting the Kd. In contrast, IL-8 was unable to prevent binding of [3H]-SB265610. Kinetic binding experiments demonstrated that this was not an artefact of irreversible or slowly reversible binding. In functional experiments, SB265610 caused a rightward shift of the concentration-response curves to IL-8 and growth-related oncogene α, but also a reduction in maximal response elicited by each agonist. Fitting these data to an operational allosteric ternary complex model suggested that, once bound, SB265610 completely blocks receptor activation. SB265610 also inhibited basal [35S]-GTPγS binding in this preparation. Conclusions and implications: Taken together, these data suggest that SB265610 behaves as an allosteric inverse agonist at the CXCR2 receptor, binding at a region distinct from the agonist binding site to prevent receptor activation, possibly by interfering with G protein coupling. PMID:19422399

Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.

PubMed

Owaki, Hiroyuki; Sadahiro, Sotaro; Takaki, Miyako

2015-04-01

Human internal anal sphincter (IAS) is contracted by α1-adrenoceptor stimulation and thus α1-adrenoceptor agonists may be useful in treating fecal incontinence. This study characterizes the contribution of α1-adrenoceptor subtypes in contraction of human IAS and to investigate the age-related risk of patients with fecal incontinence. IAS and inferior mesenteric artery (IMA), as a predictor of systemic arterial pressure, were obtained from 11 patients. Both muscle strips were assessed by isometric-contraction experiments using phenylephrine, further in IAS, in the presence of various subtype selective α1-adrenoceptor antagonists. Immunohistochemistry and gene expression studies were performed in the same samples. The mean pEC50 values with SEM of phenylephrine in IAS (6.30 ± 0.13) were higher than those of IMA (5.60 ± 0.10). Furthermore, the age-related pEC50 change of IAS was observed between age <70 and ≥70 (6.58 ± 0.13 and 6.07 ± 0.16, respectively (P < 0.05)). In IAS, rightward shift of the concentration-response curves of phenylephrine was observed with three α1-adrenoceptor antagonists. Each pKB value of silodosin, BMY-7378 and prazosin was 9.36 ± 0.53, 7.28 ± 0.20 and 8.89 ± 0.12, respectively. These pKB values and gene expression studies indicated that α1A-adrenoceptor subtypes predominantly contributed to human IAS contraction. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The dynamic effect of reading direction habit on spatial asymmetry of image perception.

PubMed

Afsari, Zaeinab; Ossandón, José P; König, Peter

2016-09-01

Exploration of images after stimulus onset is initially biased to the left. Here, we studied the causes of such an asymmetry and investigated effects of reading habits, text primes, and priming by systematically biased eye movements on this spatial bias in visual exploration. Bilinguals first read text primes with right-to-left (RTL) or left-to-right (LTR) reading directions and subsequently explored natural images. In Experiment 1, native RTL speakers showed a leftward free-viewing shift after reading LTR primes but a weaker rightward bias after reading RTL primes. This demonstrates that reading direction dynamically influences the spatial bias. However, native LTR speakers who learned an RTL language late in life showed a leftward bias after reading either LTR or RTL primes, which suggests the role of habit formation in the production of the spatial bias. In Experiment 2, LTR bilinguals showed a slightly enhanced leftward bias after reading LTR text primes in their second language. This might contribute to the differences of native RTL and LTR speakers observed in Experiment 1. In Experiment 3, LTR bilinguals read normal (LTR, habitual reading) and mirrored left-to-right (mLTR, nonhabitual reading) texts. We observed a strong leftward bias in both cases, indicating that the bias direction is influenced by habitual reading direction and is not secondary to the actual reading direction. This is confirmed in Experiment 4, in which LTR participants were asked to follow RTL and LTR moving dots in prior image presentation and showed no change in the normal spatial bias. In conclusion, the horizontal bias is a dynamic property and is modulated by habitual reading direction.

GZ-793A, a lobelane analog, interacts with the vesicular monoamine transporter-2 to inhibit the effect of methamphetamine

PubMed Central

Horton, David B.; Nickell, Justin R.; Zheng, Guangrong; Crooks, Peter A.; Dwoskin, Linda P.

2013-01-01

GZ-793A inhibits methamphetamine-evoked dopamine release from striatal slices and methamphetamine self-administration in rats. GZ-793A potently and selectively inhibits dopamine uptake at the vesicular monoamine transporter-2 (VMAT2). The present study determined GZ-793A’s ability to evoke [3H]dopamine release and inhibit methamphetamine-evoked [3H]dopamine release from isolated striatal synaptic vesicles. Results show GZ-793A concentration-dependent [3H]dopamine release; nonlinear regression revealed a two-site model of interaction with VMAT2 (High- and Low-EC50 = 15.5 nM and 29.3 µM, respectively). Tetrabenazine and reserpine completely inhibited the GZ-793A-evoked [3H]dopamine release, however, only at the High-affinity site. Low concentrations of GZ-793A that interact with the extravesicular dopamine uptake site and the High-affinity intravesicular DA release site also inhibited methamphetamine-evoked [3H]dopamine release from synaptic vesicles. A rightward shift in the methamphetamine concentration-response was evident with increasing concentrations of GZ-793A, and the Schild regression slope was 0.49±0.08, consistent with surmountable allosteric inhibition. These results support a hypothetical model of GZ-793A interaction at more than one site on VMAT2 protein, which explains its potent inhibition of dopamine uptake, dopamine release via a High-affinity tetrabenazine- and reserpine-sensitive site, dopamine release via a Low-affinity tetrabenazine- and reserpine-insensitive site, and low-affinity interaction with the dihydrotetrabenazine binding site on VMAT2. GZ-793A-inhibition of the effects of methamphetamine supports its potential as a therapeutic agent for the treatment of methamphetamine abuse. PMID:23875622

Exploring auditory neglect: Anatomo-clinical correlations of auditory extinction.

PubMed

Tissieres, Isabel; Crottaz-Herbette, Sonia; Clarke, Stephanie

2018-05-23

The key symptoms of auditory neglect include left extinction on tasks of dichotic and/or diotic listening and rightward shift in locating sounds. The anatomical correlates of the latter are relatively well understood, but no systematic studies have examined auditory extinction. Here, we performed a systematic study of anatomo-clinical correlates of extinction by using dichotic and/or diotic listening tasks. In total, 20 patients with right hemispheric damage (RHD) and 19 with left hemispheric damage (LHD) performed dichotic and diotic listening tasks. Either task consists of the simultaneous presentation of word pairs; in the dichotic task, 1 word is presented to each ear, and in the diotic task, each word is lateralized by means of interaural time differences and presented to one side. RHD was associated with exclusively contralesional extinction in dichotic or diotic listening, whereas in selected cases, LHD led to contra- or ipsilesional extinction. Bilateral symmetrical extinction occurred in RHD or LHD, with dichotic or diotic listening. The anatomical correlates of these extinction profiles offer an insight into the organisation of the auditory and attentional systems. First, left extinction in dichotic versus diotic listening involves different parts of the right hemisphere, which explains the double dissociation between these 2 neglect symptoms. Second, contralesional extinction in the dichotic task relies on homologous regions in either hemisphere. Third, ipsilesional extinction in dichotic listening after LHD was associated with lesions of the intrahemispheric white matter, interrupting callosal fibres outside their midsagittal or periventricular trajectory. Fourth, bilateral symmetrical extinction was associated with large parieto-fronto-temporal LHD or smaller parieto-temporal RHD, which suggests that divided attention, supported by the right hemisphere, and auditory streaming, supported by the left, likely play a critical role. Copyright © 2018. Published by Elsevier Masson SAS.

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin-ethanolamides) in the feline iris

PubMed Central

Woodward, D F; Krauss, A H; Wang, J W; Protzman, C E; Nieves, A L; Liang, Y; Donde, Y; Burk, R M; Landsverk, K; Struble, C

2006-01-01

Background and Purpose: The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. Experimental Approach: The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. Key Results: In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2α and the prostamide F2α analog bimatoprost but did not block the effects of PGF2α and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2α activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. Conclusions and Implications: The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2α and PGE2-glyceryl ester. PMID:17179945

Austrian Moderate Altitude Study (AMAS 2000): erythropoietic activity and Hb-O(2) affinity during a 3-week hiking holiday at moderate altitude in persons with metabolic syndrome.

PubMed

Schobersberger, Wolfgang; Greie, Sven; Humpeler, Egon; Mittermayr, Markus; Fries, Dietmar; Schobersberger, Beatrix; Artner-Dworzak, Erika; Hasibeder, Walter; Klingler, Anton; Gunga, Hanns-Christian

2005-01-01

Moderate altitude hypoxia (1500 to 2500 m) is known to stimulate erythropoiesis and to improve oxygen transport to tissue by a reduction of Hb-O(2) affinity. Whether this adaptation also occurs in tourists with metabolic syndrome has not yet been investigated sufficiently. Thus, we performed a prospective field study to measure erythropoietic parameters and oxygen transport properties in 24 male volunteers with metabolic syndrome during a 3- week holiday program at 1700 m consisting of four guided, individually adapted hiking tours per week. The following examinations were performed: baseline investigations at 500 m (T1); examinations at moderate altitude on day 1 (T2), day 4 (T3), day 9 (T4), and day 19 (T5); and postaltitude tests (T6) 7 to 10 days after return. On day 1 and day 19, a walk on a standardized hiking test route with oxygen saturation (SpO(2)) measure points was performed. Hemoglobin, packed cell volume, and red cell count showed changes over time, with higher values at T5 as compared to baseline. Reticulocyte count and erythropoietin (EPO) were increased at T2 and increased further until T5. EPO declined toward prealtitude values. P50-value (blood PO(2) at 50% hemoglobin oxygen saturation at actual pH) increased during the altitude sojourn (maximum increase at T5 by +0.40 kPa). At T5 all volunteers had a higher SpO(2) before, during, and at the end of the test route compared to T1. During adaptation to moderate altitude, persons with metabolic syndrome exhibit an increase in EPO and a rightward shift of the oxygen dissociation curve that is similar to healthy subjects.

Adult age differences in the perceptual span during reading.

PubMed

Risse, Sarah; Kliegl, Reinhold

2011-06-01

Following up on research suggesting an age-related reduction in the rightward extent of the perceptual span during reading (Rayner, Castelhano, & Yang, 2009), we compared old and young adults in an N + 2-boundary paradigm in which a nonword preview of word N + 2 or word N + 2 itself is replaced by the target word once the eyes cross an invisible boundary located after word N. The intermediate word N + 1 was always three letters long. Gaze durations on word N + 2 were significantly shorter for identical than nonword N + 2 preview both for young and for old adults, with no significant difference in this preview benefit. Young adults, however, did modulate their gaze duration on word N more strongly than old adults in response to the difficulty of the parafoveal word N + 1. Taken together, the results suggest a dissociation of preview benefit and parafoveal-on-foveal effect. Results are discussed in terms of age-related decline in resilience towards distributed processing while simultaneously preserving the ability to integrate parafoveal information into foveal processing. As such, the present results relate to proposals of regulatory compensation strategies older adults use to secure an overall reading speed very similar to that of young adults. (c) 2011 APA, all rights reserved.

The myth of the Bernheim syndrome.

PubMed

Chung, Monica S; Ko, Jo Mi; Chamogeorgakis, Themistokles; Hall, Shelley A; Roberts, William C

2013-10-01

The Bernheim syndrome has been a topic of discussion for over a century. It has been reported to be caused by severe rightward movement of the ventricular septum resulting in compression of the right ventricular cavity leading to right-sided heart failure without pulmonary congestion. Hemodynamic findings have been described in a few patients with the so-called Bernheim syndrome. We describe a patient in whom the ventricular septum dramatically decreased the size of the right ventricular cavity and yet peak systolic pressures in both the right ventricle and pulmonary trunk were identical. Thus, it is difficult to view the Bernheim syndrome as a real entity.

Effect of prism adaptation on left dichotic listening deficit in neglect patients: glasses to hear better?

PubMed

Jacquin-Courtois, S; Rode, G; Pavani, F; O'Shea, J; Giard, M H; Boisson, D; Rossetti, Y

2010-03-01

Unilateral neglect is a disabling syndrome frequently observed following right hemisphere brain damage. Symptoms range from visuo-motor impairments through to deficient visuo-spatial imagery, but impairment can also affect the auditory modality. A short period of adaptation to a rightward prismatic shift of the visual field is known to improve a wide range of hemispatial neglect symptoms, including visuo-manual tasks, mental imagery, postural imbalance, visuo-verbal measures and number bisection. The aim of the present study was to assess whether the beneficial effects of prism adaptation may generalize to auditory manifestations of neglect. Auditory extinction, whose clinical manifestations are independent of the sensory modalities engaged in visuo-manual adaptation, was examined in neglect patients before and after prism adaptation. Two separate groups of neglect patients (all of whom exhibited left auditory extinction) underwent prism adaptation: one group (n = 6) received a classical prism treatment ('Prism' group), the other group (n = 6) was submitted to the same procedure, but wore neutral glasses creating no optical shift (placebo 'Control' group). Auditory extinction was assessed by means of a dichotic listening task performed three times: prior to prism exposure (pre-test), upon prism removal (0 h post-test) and 2 h later (2 h post-test). The total number of correct responses, the lateralization index (detection asymmetry between the two ears) and the number of left-right fusion errors were analysed. Our results demonstrate that prism adaptation can improve left auditory extinction, thus revealing transfer of benefit to a sensory modality that is orthogonal to the visual, proprioceptive and motor modalities directly implicated in the visuo-motor adaptive process. The observed benefit was specific to the detection asymmetry between the two ears and did not affect the total number of responses. This indicates a specific effect of prism adaptation on lateralized processes rather than on general arousal. Our results suggest that the effects of prism adaptation can extend to unexposed sensory systems. The bottom-up approach of visuo-motor adaptation appears to interact with higher order brain functions related to multisensory integration and can have beneficial effects on sensory processing in different modalities. These findings should stimulate the development of therapeutic approaches aimed at bypassing the affected sensory processing modality by adapting other sensory modalities.

Development of an anaesthetized-rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram.

PubMed

Miyamoto, Tadayoshi; Manabe, Kou; Ueda, Shinya; Nakahara, Hidehiro

2018-05-01

What is the central question of this study? The lack of useful small-animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise-induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized-rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. Exercise-induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized-rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath-by-breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end-tidal CO 2 pressure (P ETC O2) and minute ventilation (V̇E), and the plant by the hyperbolic relationship between V̇E and P ETC O2. During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity-dependent changes in operating points (V̇E and P ETC O2) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized-rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. © 2018 Morinomiya University of Medical Sciences. Experimental Physiology © 2018 The Physiological Society.

Modulation of chloride, potassium and bicarbonate transport by muscarinic receptors in a human adenocarcinoma cell line.

PubMed

Holliday, N D; Cox, H M

1999-01-01

1. Short-circuit current (I(SC)) responses to carbachol (CCh) were investigated in Colony 1 epithelia, a subpopulation of the HCA-7 adenocarcinoma cell line. In Krebs-Henseleit (KH) buffer, CCh responses consisted of three I(SC) components: an unusual rapid decrease (the 10 s spike) followed by an upward spike at 30 s and a slower transient increase (the 2 min peak). This response was not potentiated by forskolin; rather, CCh inhibited cyclic AMP-stimulated I(SC). 2. In HCO3- free buffer, the decrease in forskolin-elevated I(SC) after CCh was reduced, although the interactions between CCh and forskolin remained at best additive rather than synergistic. When Cl- anions were replaced by gluconate, both Ca2+- and cyclic AMP-mediated electrogenic responses were significantly inhibited. 3. Basolateral Ba2+ (1-10 mM) and 293B (10 microM) selectively inhibited forskolin stimulation of I(SC), without altering the effects of CCh. Under Ba2+- or 293B-treated conditions, CCh responses were potentiated by pretreatment with forskolin. 4. Basolateral charybdotoxin (50 nM) significantly increased the size of the 10 s spike of CCh responses in both KH and HCO3- free medium, without affecting the 2 min peak. The enhanced 10 s spike was inhibited by prior addition of 5 mM apical Ba2+. Charybdotoxin did not affect forskolin responses. 5. In epithelial layers prestimulated with forskolin, the muscarinic antagonists atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, both at 100 nM) abolished subsequent 10 microM CCh responses. Following addition of p-fluoro hexahydro-sila-difenidol (pF-HHSiD, 10 microM) or pirenzepine (1 microM), qualitative changes in the CCh response time-profile also indicated a rightward shift of the agonist concentration-response curve; however, 1 microM gallamine had no effect. These results suggest that a single M3-like receptor subtype mediates the secretory response to CCh. 6. It is concluded that CCh and forskolin activate discrete populations of basolateral K+ channels gated by either Ca2+ or cyclic AMP, but that the Cl- permeability of the apical membrane may limit their combined effects on electrogenic Cl- secretion. In addition, CCh activates a Ba2+-sensitive apical K+ conductance leading to electrogenic K+ transport. Both agents may also modulate HCO3- secretion through a mechanism at least partially dependent on carbonic anhydrase.

The eye movements of dyslexic children during reading and visual search: impact of the visual attention span.

PubMed

Prado, Chloé; Dubois, Matthieu; Valdois, Sylviane

2007-09-01

The eye movements of 14 French dyslexic children having a VA span reduction and 14 normal readers were compared in two tasks of visual search and text reading. The dyslexic participants made a higher number of rightward fixations in reading only. They simultaneously processed the same low number of letters in both tasks whereas normal readers processed far more letters in reading. Importantly, the children's VA span abilities related to the number of letters simultaneously processed in reading. The atypical eye movements of some dyslexic readers in reading thus appear to reflect difficulties to increase their VA span according to the task request.

Self-motion Perception Training: Thresholds Improve in the Light but not in the Dark

PubMed Central

Hartmann, Matthias; Furrer, Sarah; Herzog, Michael H.; Merfeld, Daniel M.; Mast, Fred W.

2014-01-01

We investigated perceptual learning in self-motion perception. Blindfolded participants were displaced leftward or rightward by means of a motion platform, and asked to indicate the direction of motion. A total of eleven participants underwent 3360 practice trials, distributed over twelve (Experiment 1) or six days (Experiment 2). We found no improvement in motion discrimination in both experiments. These results are surprising since perceptual learning has been demonstrated for visual, auditory, and somatosensory discrimination. Improvements in the same task were found when visual input was provided (Experiment 3). The multisensory nature of vestibular information is discussed as a possible explanation of the absence of perceptual learning in darkness. PMID:23392475

Mechanisms involved in the relaxant action of the ethanolic extract of propolis in the guinea-pig trachea in-vitro.

PubMed

Paulino, Niraldo; Scremin, Fernando M; Raichaski, Lisiane B; Marcucci, Maria Cristina; Scremin, Amarilis; Calixto, João B

2002-06-01

This study examines the mechanisms by which the standardised ethanolic extract of propolis induces relaxation of the guinea-pig trachea in-vitro. In guinea-pig trachea with or without epithelium and contracted by histamine, the propolis extract caused reproducible and graded relaxation, with a mean EC50 value of 3.8 or 10.5 microg mL(-1) and Emax of 100%, respectively. The propolis extract-induced relaxation was markedly reduced (26+/-9 and 96+/-3%) when guinea-pig tracheas were exposed to Krebs solution containing elevated K+ in the medium (40 or 80 mM). Pre-incubation of guinea-pig tracheas with tetraethylamonium (100 mM) or with 4-aminopyridine (10mM) reduced the propolis extract-induced relaxation by 31+/-10% and 28+/-2%. Likewise, apamin (0.1 microM), charybdotoxin (0.1 microM) or iberiotoxin (0.1 microM) caused marked inhibition of propolis extract-mediated relaxation in guinea-pig trachea (percentage of inhibition: 65+/-3%, 60+/-5% and 65+/-9%, respectively). Also, glibenclamide (1 microM) inhibited the relaxant response caused by the propolis extract by 57+/-4%. Omega-conotoxin GIVA (0.1 microM) or capsaicin (1 microM) produced small but significant inhibition (30+/-5% or 47+/-7%, respectively) of the propolis extract-induced relaxation. The vasoactive intestinal peptide (VIP) antagonist D-p-Cl-Phe6,Leu17[VIP] porcine (0.1 microM) inhibited relaxation by 55+/-5%, while propranolol (1 microM) induced a parallel rightward displacement (about 20 fold) of the propolis extract concentration-response curve. Finally, the propolis extract-induced relaxation was inhibited by the nitric oxide synthase inhibitor L-N(G)-nitroarginine (L-NOArg, 100 microM) (48+/-6%), and by the soluble guanylatecyclase inhibitormethylene blue (10 microM) (37+/-6%), whilethe moreselectivesoluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolol[4,3-alquinoxalin-1-one (ODQ, 1 microM) produced only a parallel (about 3 fold) rightward displacement of the propolis extract concentration-response curve. Collectively, these results support the notion that the propolis extract-mediated relaxation in the guinea-pig trachea involves the release of nitric oxide, probably from sensory neurons, besides the activation of soluble guanylate cyclase and activation of Ca2+- and ATP-sensitive K+ channels. Furthermore, the stimulation of beta2-adrenergic and VIP receptors also seems to account for its relaxant action.

Believing androids - fMRI activation in the right temporo-parietal junction is modulated by ascribing intentions to non-human agents.

PubMed

Özdem, Ceylan; Wiese, Eva; Wykowska, Agnieszka; Müller, Hermann; Brass, Marcel; Van Overwalle, Frank

2017-10-01

Attributing mind to interaction partners has been shown to increase the social relevance we ascribe to others' actions and to modulate the amount of attention dedicated to them. However, it remains unclear how the relationship between higher-order mind attribution and lower-level attention processes is established in the brain. In this neuroimaging study, participants saw images of an anthropomorphic robot that moved its eyes left- or rightwards to signal the appearance of an upcoming stimulus in the same (valid cue) or opposite location (invalid cue). Independently, participants' beliefs about the intentionality underlying the observed eye movements were manipulated by describing the eye movements as under human control or preprogrammed. As expected, we observed a validity effect behaviorally and neurologically (increased response times and activation in the invalid vs. valid condition). More importantly, we observed that this effect was more pronounced for the condition in which the robot's behavior was believed to be controlled by a human, as opposed to be preprogrammed. This interaction effect between cue validity and belief was, however, only found at the neural level and was manifested as a significant increase of activation in bilateral anterior temporoparietal junction.

Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.

PubMed

Springer, J A; Binder, J R; Hammeke, T A; Swanson, S J; Frost, J A; Bellgowan, P S; Brewer, C C; Perry, H M; Morris, G L; Mueller, W M

1999-11-01

Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.

The thinker: opposing directionality of lighting bias within sculptural artwork

PubMed Central

Sedgewick, Jennifer R.; Weiers, Bradley; Stewart, Aaron; Elias, Lorin J.

2015-01-01

Individuals tend to perceive the direction of light to come from above and slightly from the left; it has been speculated that this phenomenon is also producing similar lighting preferences within 2-dimensional artworks (e.g., paintings, advertisements). The purpose of the present study was to address if lighting bias was present in the 3-dimensional medium of sculpture by implementing a virtual art gallery lighting paradigm. Thirty-nine participants completed a computer task that consisted of 48 galleries each containing one sculpture (24 original sculptures, 24 mirror-reversed) which was surrounded by eight lights (above/below, left/right, front/back). Participants would select one light source to illuminate the sculpture in a manner they perceived to be the most aesthetically pleasing. The results indicated a significant preference for lights positioned from above and from the right, a finding that is contradictory to previous lighting bias research examining artworks. An interpretation for the rightward bias applies the perceptual concept of subjective lighting equality. Objects illuminated from the left typically appear brighter in comparison to right-side lighting; in sculpture, however, increased luminosity can reduce the sculptural detail, and may have been compensated via right-side lighting choices within the lighting task. PMID:25999840

Evaluation of the calcium-antagonist, antidiarrhoeic and central nervous system activities of Baccharis serraefolia.

PubMed

Tortoriello, J; Aguilar-Santamaría, L

1996-09-01

Baccharis serraefolia is a widely used plant to treat diarrhoea in Mexican traditional medicine. Although the methanolic extract of this plant has shown an important dose-dependent spasmolytic activity, its underlying mechanism has not been studied. In the present work, the methanolic extract of B. serraefolia significantly delayed the onset of tonic seizures induced by strychnine and pentylenetetrazol; besides, it diminished the death rate and number of animals that exhibited convulsions. It produced potentiation of the hypnotic effect of pentobarbital. Oral administration produced an inhibition of gastrointestinal transit in mice as effective as that produced by loperamide. As to the effect on smooth muscles, the active extract produced an inhibition of contraction induced electrically, which could not be reversed by naloxone. The calcium concentration-contraction curve showed a rightward displacement when the extract was added to isolated guinea pig ileum depolarized with high K+ and cumulative concentrations of Ca2+. The results suggest that the methanolic extract does not interact with classical opiate receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intra-cellular store.

Learning to predict is spared in mild cognitive impairment due to Alzheimer's disease.

PubMed

Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-10-01

Learning the statistics of the environment is critical for predicting upcoming events. However, little is known about how we translate previous knowledge about scene regularities to sensory predictions. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are known to have spared implicit but impaired explicit recognition memory are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards oriented gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. Further, we show that executive cognitive control may account for individual variability in predictive learning. That is, we observed significant positive correlations of performance in attentional and working memory tasks with post-training performance in the prediction task. Taken together, these results suggest a mediating role of circuits involved in cognitive control (i.e. frontal circuits) that may support the ability for predictive learning in MCI-AD.

Projecting one’s own spatial bias onto others during a theory-of-mind task

PubMed Central

Bio, Branden J.; Webb, Taylor W.; Graziano, Michael S. A.

2018-01-01

Many people show a left-right bias in visual processing. We measured spatial bias in neurotypical participants using a variant of the line bisection task. In the same participants, we measured performance in a social cognition task. This theory-of-mind task measured whether each participant had a processing-speed bias toward the right of, or left of, a cartoon agent about which the participant was thinking. Crucially, the cartoon was rotated such that what was left and right with respect to the cartoon was up and down with respect to the participant. Thus, a person’s own left-right bias could not align directly onto left and right with respect to the cartoon head. Performance on the two tasks was significantly correlated. People who had a natural bias toward processing their own left side of space were quicker to process how the cartoon might think about objects to the left side of its face, and likewise for a rightward bias. One possible interpretation of these results is that the act of processing one’s own personal space shares some of the same underlying mechanisms as the social cognitive act of reconstructing someone else’s processing of their space. PMID:29339513

Long-term sensorimotor and therapeutical effects of a mild regime of prism adaptation in spatial neglect. A double-blind RCT essay.

PubMed

Rode, G; Lacour, S; Jacquin-Courtois, S; Pisella, L; Michel, C; Revol, P; Alahyane, N; Luauté, J; Gallagher, S; Halligan, P; Pélisson, D; Rossetti, Y

2015-04-01

Spatial neglect (SN) is commonly associated with poor functional outcome. Adaptation to a rightward optical deviation of vision has been shown to benefit to SN rehabilitation. The neurophysiological foundations and the optimal modalities of prism adaptation (PA) therapy however remain to be validated. This study is aimed at exploring the long-term sensory-motor, cognitive and functional effects produced by weekly PA sessions over a period of four weeks. A double-blind, monocentric randomized and controlled trial (RCT) was carried out. Twenty patients with left SN secondary to stroke were included, 10 in the "prism" group and 10 in the "control" group. The sensory-motor effects of PA were evaluated by measurement of manual and visual straight-ahead, and also by precision of pointing without visual feedback before and after each PA session. The functional independence measure (FIM) was evaluated before and at 1, 3 and 6 months after PA, while SN severity was assessed using the Behavioural Inattention Test (BIT) before and 6 months after PA. Before the intervention, only manual straight-ahead pointing constituted a reproducible sensory-motor measurement. During prism exposure, a questionnaire showed that not a single patient were aware of the direct effects of optical deviation on pointing movement performance. The sensory-motor after-effects produced by the PA produced a more rapid reduction of the rightward manual straight-ahead, which was secondarily followed by visual straight-ahead. These sensory-motor effects helped to clarify the action mechanisms of PA on SN. At the conclusion of the 6-month follow-up, the two groups showed similar improvement, indicating that a weekly PA session over 4 weeks was not sufficient to produce long-term functional benefit. This improvement was correlated with the evolution of visual straight-ahead, which can be proposed as a marker for patients outcome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The association between hemispheric specialization for language production and for spatial attention depends on left-hand preference strength.

PubMed

Zago, Laure; Petit, Laurent; Mellet, Emmanuel; Jobard, Gaël; Crivello, Fabrice; Joliot, Marc; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

2016-12-01

Cerebral lateralization for language production and spatial attention and their relationships with manual preference strength (MPS) were assessed in a sample of 293 healthy volunteers, including 151 left-handers, using fMRI during covert sentence production (PROD) and line bisection judgment (LBJ) tasks, as compared to high- and low-level reference tasks. At the group level, we found the expected complementary hemispheric specialization (HS) with leftward asymmetries for PROD within frontal and temporal regions and rightward asymmetries for LBJ within frontal and posterior occipito-parieto-temporal regions. Individual hemispheric (HLI) and regional (frontal and occipital) lateralization indices (LI) were then calculated on the activation maps for PROD and LBJ. We found a correlation between the degree of rightward cerebral asymmetry and the leftward behavioral attentional bias recorded during LBJ task. This correlation was found when LBJ-LI was computed over the hemispheres, in the frontal lobes, but not in the occipital lobes. We then investigated whether language production and spatial attention cerebral lateralization relate to each other, and whether manual preference was a variable that impacted the complementary HS of these functions. No correlation was found between spatial and language LIs in the majority of our sample of participants, including right-handers with a strong right-hand preference (sRH, n=97) and mixed-handers (MH, n=97), indicating that these functions lateralized independently. By contrast, in the group of left-handers with a strong left-hand preference (sLH, n= 99), a negative correlation was found between language and spatial lateralization. This negative correlation was found when LBJ-LI and PROD-LI were computed over the hemispheres, in the frontal lobes and between the occipital lobes for LBJ and the frontal lobes for PROD. These findings underline the importance to include sLH in the study sample to reveal the underlying mechanisms of complementary HS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experience-dependent enhancement of pitch-specific responses in the auditory cortex is limited to acceleration rates in normal voice range

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Suresh, Chandan H.

2015-01-01

The aim of this study is to determine how pitch acceleration rates within and outside the normal pitch range may influence latency and amplitude of cortical pitch-specific responses (CPR) as a function of language experience (Chinese, English). Responses were elicited from a set of four pitch stimuli chosen to represent a range of acceleration rates (two each inside and outside the normal voice range) imposed on the high rising Mandarin Tone 2. Pitch-relevant neural activity, as reflected in the latency and amplitude of scalp-recorded CPR components, varied depending on language-experience and pitch acceleration of dynamic, time-varying pitch contours. Peak latencies of CPR components were shorter in the Chinese than the English group across stimuli. Chinese participants showed greater amplitude than English for CPR components at both frontocentral and temporal electrode sites in response to pitch contours with acceleration rates inside the normal voice pitch range as compared to pitch contours with acceleration rates that exceed the normal range. As indexed by CPR amplitude at the temporal sites, a rightward asymmetry was observed for the Chinese group only. Only over the right temporal site was amplitude greater in the Chinese group relative to the English. These findings may suggest that the neural mechanism(s) underlying processing of pitch in the right auditory cortex reflect experience-dependent modulation of sensitivity to acceleration in just those rising pitch contours that fall within the bounds of one’s native language. More broadly, enhancement of native pitch stimuli and stronger rightward asymmetry of CPR components in the Chinese group is consistent with the notion that long-term experience shapes adaptive, distributed hierarchical pitch processing in the auditory cortex, and reflects an interaction with higher-order, extrasensory processes beyond the sensory memory trace. PMID:26166727

Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma

PubMed Central

2010-01-01

Background BamHI-A rightward frame-1 (BARF1) is a carcinoma-specific Epstein-Barr virus (EBV) encoded oncogene. Here we describe the BARF1 sequence diversity in nasopharyngeal carcinoma (NPC), other EBV-related diseases and Indonesian healthy EBV carriers in relation to EBV genotype, viral load and serology markers. Nasopharyngeal brushings from 56 NPC cases, blood or tissue from 15 other EBV-related disorders, spontaneous B cell lines (LCL) from 5 Indonesian healthy individuals and several prototype EBV isolates were analysed by PCR-direct sequencing. Results Most NPC isolates revealed specific BARF1 nucleotide changes compared to prototype B95-8 virus. At the protein level these mutations resulted in 3 main substitutions (V29A, W72G, H130R), which are not considered to cause gross tertiary structure alterations in the hexameric BARF1 protein. At least one amino acid conversion was detected in 80.3% of NPC samples compared to 33.3% of non-NPC samples (p < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence. Conclusion The sequence variation of BARF1 observed in Indonesian NPC patients and controls may reflect a natural selection of EBV strains unlikely to be predisposing to carcinogenesis. The conserved nature of BARF1 may reflect an important role in EBV (epithelial) persistence. PMID:20849661

Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma.

PubMed

Hutajulu, Susanna H; Hoebe, Eveline K; Verkuijlen, Sandra Awm; Fachiroh, Jajah; Hariwijanto, Bambang; Haryana, Sofia M; Stevens, Servi Jc; Greijer, Astrid E; Middeldorp, Jaap M

2010-09-19

BamHI-A rightward frame-1 (BARF1) is a carcinoma-specific Epstein-Barr virus (EBV) encoded oncogene. Here we describe the BARF1 sequence diversity in nasopharyngeal carcinoma (NPC), other EBV-related diseases and Indonesian healthy EBV carriers in relation to EBV genotype, viral load and serology markers. Nasopharyngeal brushings from 56 NPC cases, blood or tissue from 15 other EBV-related disorders, spontaneous B cell lines (LCL) from 5 Indonesian healthy individuals and several prototype EBV isolates were analysed by PCR-direct sequencing. Most NPC isolates revealed specific BARF1 nucleotide changes compared to prototype B95-8 virus. At the protein level these mutations resulted in 3 main substitutions (V29A, W72G, H130R), which are not considered to cause gross tertiary structure alterations in the hexameric BARF1 protein. At least one amino acid conversion was detected in 80.3% of NPC samples compared to 33.3% of non-NPC samples (p < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence. The sequence variation of BARF1 observed in Indonesian NPC patients and controls may reflect a natural selection of EBV strains unlikely to be predisposing to carcinogenesis. The conserved nature of BARF1 may reflect an important role in EBV (epithelial) persistence.

Generalized Couette Poiseuille flow with boundary mass transfer

NASA Astrophysics Data System (ADS)

Marques, F.; Sanchez, J.; Weidman, P. D.

1998-11-01

A generalized similarity formulation extending the work of Terrill (1967) for Couette Poiseuille flow in the annulus between concentric cylinders of infinite extent is given. Boundary conditions compatible with the formulation allow a study of the effects of inner and outer cylinder transpiration, rotation, translation, stretching and twisting, in addition to that of an externally imposed constant axial pressure gradient. The problem is governed by [eta], the ratio of inner to outer radii, a Poiseuille number, and nine Reynolds numbers. Single-cylinder and planar problems can be recovered in the limits [eta][rightward arrow]0 and [eta][rightward arrow]1, respectively. Two coupled primary nonlinear equations govern the meridional motion generated by uniform mass flux through the porous walls and the azimuthal motion generated by torsional movement of the cylinders; subsidiary equations linearly slaved to the primary flow govern the effects of cylinder translation, cylinder rotation, and an external pressure gradient. Steady solutions of the primary equations for uniform source/sink flow of strength F through the inner cylinder are reported for 0[less-than-or-eq, slant][eta][less-than-or-eq, slant]1. Asymptotic results corroborating the numerical solutions are found in different limiting cases. For F<0 fluid emitted through the inner cylinder fills the gap and flows uniaxially down the annulus; an asymptotic analysis leads to a scaling that removes the effect of [eta] in the pressure parameter [beta], namely [beta]=[pi]2R*2, where R*=F(1[minus sign][eta])/(1+[eta]). The case of sink flow for F>0 is more complex in that unique solutions are found at low Reynolds numbers, a region of triple solutions exists at moderate Reynolds numbers, and a two-cell solution prevails at large Reynolds numbers. The subsidiary linear equations are solved at [eta]=0.5 to exhibit the effects of cylinder translation, rotation, and an axial pressure gradient on the source/sink flows.

Investigating daily fatigue scores during two-week offshore day shifts.

PubMed

Riethmeister, Vanessa; Bültmann, Ute; Gordijn, Marijke; Brouwer, Sandra; de Boer, Michiel

2018-09-01

This study examined daily scores of fatigue and circadian rhythm markers over two-week offshore day shift periods. A prospective cohort study among N = 60 offshore day-shift workers working two-week offshore shifts was conducted. Offshore day shifts lasted from 07:00 - 19:00 h. Fatigue was measured objectively with pre- and post-shift scores of the 3-minute psychomotor vigilance tasks (PVT-B) parameters (reaction times, number of lapses, errors and false starts) and subjectively with pre- and post-shift Karolinska Sleepiness Scale (KSS) ratings. Evening saliva samples were collected on offshore days 2,7 and 13 to measure circadian rhythm markers such as dim-light melatonin onset times and cortisol. Generalized and linear mixed model analyses were used to examine daily fatigue scores over time. Complete data from N = 42 offshore day shift workers was analyzed. Daily parameters of objective fatigue, PVT-B scores (reaction times, average number of lapses, errors and false starts), remained stable over the course of the two-week offshore day shifts. Daily subjective post-shift fatigue scores significantly increased over the course of the two-week offshore shifts. Each day offshore was associated with an increased post-shift subjective fatigue score of 0.06 points (95%CI: .03 - .09 p < .001). No significant statistical differences in subjective pre-shift fatigue scores were found. Neither a circadian rhythm phase shift of melatonin nor an effect on the pattern and levels of evening cortisol was found. Daily parameters of objective fatigue scores remained stable over the course of the two-week offshore day shifts. Daily subjective post-shift fatigue scores significantly increased over the course of the two-week offshore shifts. No significant changes in circadian rhythm markers were found. Increased post-shift fatigue scores, especially during the last days of an offshore shift, should be considered and managed in (offshore) fatigue risk management programs and fatigue risk prediction models. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impact of shift work and organizational work climate on health outcomes in nurses.

PubMed

von Treuer, Kathryn; Fuller-Tyszkiewicz, Matthew; Little, Glenn

2014-10-01

Shift workers have a higher rate of negative health outcomes than day shift workers. Few studies however, have examined the role of difference in workplace environment between shifts itself on such health measures. This study investigated variation in organizational climate across different types of shift work and health outcomes in nurses. Participants (n = 142) were nursing staff from a metropolitan Melbourne hospital. Demographic items elicited the type of shift worked, while the Work Environment Scale and the General Health Questionnaire measured organizational climate and health respectively. Analysis supported the hypotheses that different organizational climates occurred across different shifts, and that different organizational climate factors predicted poor health outcomes. Shift work alone was not found to predict health outcomes. Specifically, permanent night shift workers had significantly lower coworker cohesion scores compared with rotating day and evening shift workers and significantly higher managerial control scores compared with day shift workers. Further, coworker cohesion and involvement were found to be significant predictors of somatic problems. These findings suggest that differences in organizational climate between shifts accounts for the variation in health outcomes associated with shift work. Therefore, increased workplace cohesion and involvement, and decreased work pressure, may mitigate the negative health outcomes of shift workers. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

PubMed

Wang, Xinrui; Fitts, Robert H

2017-08-01

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic receptor agonist dose-response curve rightward compared with controls by reducing β 1 -adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher K ATP channel function. Copyright © 2017 the American Physiological Society.

Synthesis, structures and properties of the new lithium cobalt(II) phosphate Li{sub 4}Co(PO{sub 4}){sub 2}

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

Glaum, R., E-mail: rglaum@uni-bonn.de; Gerber, K.; Schulz-Dobrick, M.

2012-04-15

{alpha}-Li{sub 4}Co(PO{sub 4}){sub 2} has been synthesized and crystallized by solid-state reactions. The new phosphate crystallizes in the monoclinic system (P2{sub 1}/a, Z=4, a=8.117(3) Angstrom-Sign , b=10.303(8) Angstrom-Sign , c=8.118(8) Angstrom-Sign , {beta}=104.36(8) Angstrom-Sign ) and is isotypic to {alpha}-Li{sub 4}Zn(PO{sub 4}){sub 2}. The structure of {alpha}-Li{sub 4}Co(PO{sub 4}){sub 2} has been determined from single-crystal X-ray diffraction data {l_brace}R{sub 1}=0.040, wR{sub 2}=0.135, 2278 unique reflections with F{sub o}>4{sigma}(F{sub o}){r_brace}. The crystal structure, which might be regarded as a superstructure of the wurtzite structure type, is build of layers of regular CoO{sub 4}, PO{sub 4} and Li1O{sub 4} tetrahedra. Lithium atomsmore » Li2, Li3 and Li4 are located between these layers. Thermal investigations by in-situ XRPD, DTA/TG and quenching experiments suggest decomposition followed by formation and phase transformation of Li{sub 4}Co(PO{sub 4}){sub 2}: {alpha}-Li{sub 4}Co(PO{sub 4}){sub 2} Long-Rightwards-Double-Arrow {sup 442 Degree-Sign C}{beta}-Li{sub 3}PO{sub 4}+LiCoPO{sub 4} Rightwards-Harpoon-Over-Leftwards-Harpoon {sup 773 Degree-Sign C}{beta}-Li{sub 4}Co(PO{sub 4}){sub 2} Long-Rightwards-Double-Arrow {sup quenchingto25 Degree-Sign C}{alpha}-Li{sub 4} Co(PO{sub 4}){sub 2} According to HT-XRPD at {theta}=850 Degree-Sign C{beta}-Li{sub 4}Co(PO{sub 4}){sub 2} (Pnma, Z=2, 10.3341(8) A, b=6.5829(5) A, c=5.0428(3) Angstrom-Sign ) is isostructural to {gamma}-Li{sub 3}PO{sub 4}. The powder reflectance spectrum of {alpha}-Li{sub 4}Co(PO{sub 4}){sub 2} shows the typical absorption bands for the tetrahedral chromophore [Co{sup II}O{sub 4}]. - Graphical abstract: The complex formation and decomposition behavior of Li{sub 4}Co(PO{sub 4}){sub 2} with temperature has been elucidated. The crystal structure of its {alpha}-phase was determined from single crystal data, HT-XRPD allowed derivation of a structure model for the {beta}-phase. Both modifications belong to the Li{sub 3}PO{sub 4} structure family. Highlights: Black-Right-Pointing-Pointer Li{sub 4}Co(PO{sub 4}){sub 2} exhibits complex thermal behavior. Black-Right-Pointing-Pointer The new phosphate belongs to the Li{sub 3}PO{sub 4} structure family. Black-Right-Pointing-Pointer A single-crystal structure analysis is provided for the metastable {alpha}-Li{sub 4}Co(PO{sub 4}){sub 2}. Black-Right-Pointing-Pointer From HT-XRPD data a cation distribution model is developed for {beta}-Li{sub 4}Co(PO{sub 4}){sub 2}. Black-Right-Pointing-Pointer No electrochemical delithiation is observed up to 5 V.« less

Associations between number of consecutive night shifts and impairment of neurobehavioral performance during a subsequent simulated night shift.

PubMed

Magee, Michelle; Sletten, Tracey L; Ferguson, Sally A; Grunstein, Ronald R; Anderson, Clare; Kennaway, David J; Lockley, Steven W; Rajaratnam, Shantha Mw

2016-05-01

This study aimed to investigate sleep and circadian phase in the relationships between neurobehavioral performance and the number of consecutive shifts worked. Thirty-four shift workers [20 men, mean age 31.8 (SD 10.9) years] worked 2-7 consecutive night shifts immediately prior to a laboratory-based, simulated night shift. For 7 days prior, participants worked their usual shift sequence, and sleep was assessed with logs and actigraphy. Participants completed a 10-minute auditory psychomotor vigilance task (PVT) at the start (~21:00 hours) and end (~07:00 hours) of the simulated night shift. Mean reaction times (RT), number of lapses and RT distribution was compared between those who worked 2-3 consecutive night shifts versus those who worked 4-7 shifts. Following 4-7 shifts, night shift workers had significantly longer mean RT at the start and end of shift, compared to those who worked 2-3 shifts. The slowest and fastest 10% RT were significantly slower at the start, but not end, of shift among participants who worked 4-7 nights. Those working 4-7 nights also demonstrated a broader RT distribution at the start and end of shift and had significantly slower RT based on cumulative distribution analysis (5 (th), 25 (th), 50 (th), 75 (th)percentiles at the start of shift; 75th percentile at the end of shift). No group differences in sleep parameters were found for 7 days and 24 hours prior to the simulated night shift. A greater number of consecutive night shifts has a negative impact on neurobehavioral performance, likely due to cognitive slowing.

Deblending Microlensing Events Using Astrometric Shifts

NASA Astrophysics Data System (ADS)

Goldberg, D. M.; Wozniak, P.; Paczynski, B.

1997-12-01

In this poster, we present the prospect that astrometric shifts can be used to identify blended microlensing events in crowded fields. Moreover, by measuring an astrometric shift, one can determine the position of the true lensed star with respect to the local field with very high precision. We first perform several simulations of microlensing searches in crowded fields and find that if we assume a dark lens, and that the lensed star obeys a power law luminosity function, n(L)~ L(-beta ) , over half the simulated events show a measurable astrometric shift. For simulations of 20000 stars on a 256x 256 Nyquist sampled CCD frame, we found that with beta =2, 58% of the events were significantly blended (F_{*}/Ftot <= 0.9), and of those, 73% had a large astrometric shift (>= 0.5 pixels). For beta =3, we found that 85% were significantly blended, and that 85% of those had a significant shift. Since we expect most blended events to show a significant shift, we look in the OGLE I database (Wozniak & Szymanski 1997), and find measurable and systematic shifts in over half the candidate microlensing events, including OGLE # 5, which was considered to be blended from photometric data.

Sleep quality in nurses: a randomized clinical trial of day and night shift workers.

PubMed

Niu, Shu-Fen; Chu, Hsin; Chung, Min-Huey; Lin, Chun-Chieh; Chang, Yu-Shiun; Chou, Kuei-Ru

2013-07-01

The study investigated the number of days off nurses working night shifts need to recover their sleep quality to the level of daytime workers during their days off. This study included 30 day-shift nurses and 32 night-shift nurses. It was conducted as a randomized clinical trial in the medical and surgical wards of a medical center in northern Taiwan in May and June 2010 using sleep diaries and sleep parameters collected by actigraphy on different workdays and days off. On workdays, the night-shift group had significantly less total sleep time (TST) on Day 5 and significantly lower sleep efficiency (SE) on Day 3 than the day-shift group. TSTs of the two groups on days off were higher than those on workdays. On the 4th consecutive day off, higher TST, a decrease in WASO, and an increase in SE suggests that the night-shift group had recovered their sleep quality to the level of the day-shift group on their days off. The SE of the night-shift group exceeded that of the day-shift group after the 4th consecutive day off, though the difference was not statistically significant in the present study. Based on these data, it is recommended that night-shift workers arrange a period of at least 4 days off after 5 consecutive night shifts and at least 5 days off if the staff who have previously worked night shifts are being assigned a set of different shifts.

Shift work and age as interactive predictors of body mass index among offshore workers.

PubMed

Parkes, Katharine R

2002-02-01

This study investigated shift pattern (day shifts versus day-night rotation) and its interactions with age, and with years of shiftwork exposure, as predictors of body mass index (BMI). Survey data were collected from offshore personnel working day shifts (N=787) or day-night shifts (N=787); information was obtained about shift pattern and years of shiftwork exposure, height, weight, demographic factors, and smoking habits. Hierarchical multiple regression was used to test a model in which BMI was predicted by additive and interactive effects of shift pattern, age, and exposure years with control for confounding variables. In a multivariate analysis (controlling for job type, education and smoking), BMI was predicted by the main effects of age and years of shiftwork exposure. Shift pattern was not significant as a main effect, but it interacted significantly with the curvilinear age term and with the linear and curvilinear components of shiftwork exposure. In the day shift group, age but not exposure predicted BMI; the opposite was true of the day-night shift group. The increase in BMI with an increase in age and exposure years was steeper for the day-night shift group than for the day shift group. The significant interaction effects found in this study were consistent with the view that continued exposure to day-night shift work gives rise to increases in BMI, over and above the normative effects of ageing on BMI shown by day-shift workers.

Association of salivary cortisol with chronomics of 24 hours ambulatory blood pressure/heart rate among night shift workers.

PubMed

Anjum, B; Verma, N S; Tiwari, S; Singh, R; Mahdi, A A; Singh, R B; Singh, R K

2011-08-01

Recent studies indicate a circadian rhythm in blood pressure and heart rate and its association with various neurotransmitters. In the present study, we examine the circadian nature of blood pressure/heart rate and salivary cortisol in night shift workers and whether these circadian changes produced by night shifts are reversible. Sixteen healthy nurses of both genders, aged 20-40 years, performing day and night shift duties, were randomly selected out of 22 who volunteered for this study. Ambulatory blood pressure monitoring was done in all the subjects and salivary cortisol levels were analyzed during both day and night shift duties. There were clinically significant changes in the Acrophase of blood pressure and cortisol levels, indicating ecphasia (odd timing of systolic blood pressure) individually during night as well as day shifts. However, this pattern was statistically not significant. A reverse pattern of Acrophase was observed in 8 out of 16 subjects when they were posted on day shift. No significant change was found in midline estimating statistics of rhythm (MESOR) of blood pressure values. Changes in Double amplitude (Predictable change) were observed in 8 subjects during night shifts as well as in 7 subjects during day shifts. However, the pattern was not similar and night workers had an altered circadian pattern in the night as well as during day shifts. Changes in Double amplitude, Acrophase and Salivary cortisol were found during night as well as day shifts but these changes were not statistically significant (p > 0.05) due to incomplete recovery during day shifts (changes again seen when they came back to day shifts). Salivary cortisol levels were lowest in early morning, increased at midnight and further increased in the afternoon during night shifts along with ecphasia. It is possible that nurses working the night shift felt more tired due to the altered circadian cycle.

Shift work schedule and night work load: Effects on body mass index - a four-year longitudinal study.

PubMed

Buchvold, Hogne Vikanes; Pallesen, Ståle; Waage, Siri; Bjorvatn, Bjørn

2018-05-01

Objectives The aim of this study was to investigate changes in body mass index (BMI) between different work schedules and different average number of yearly night shifts over a four-year follow-up period. Methods A prospective study of Norwegian nurses (N=2965) with different work schedules was conducted: day only, two-shift rotation (day and evening shifts), three-shift rotation (day, evening and night shifts), night only, those who changed towards night shifts, and those who changed away from schedules containing night shifts. Paired student's t-tests were used to evaluate within subgroup changes in BMI. Multiple linear regression analysis was used to evaluate between groups effects on BMI when adjusting for BMI at baseline, sex, age, marital status, children living at home, and years since graduation. The same regression model was used to evaluate the effect of average number of yearly night shifts on BMI change. Results We found that night workers [mean difference (MD) 1.30 (95% CI 0.70-1.90)], two shift workers [MD 0.48 (95% CI 0.20-0.75)], three shift workers [MD 0.46 (95% CI 0.30-0.62)], and those who changed work schedule away from [MD 0.57 (95% CI 0.17-0.84)] or towards night work [MD 0.63 (95% CI 0.20-1.05)] all had significant BMI gain (P<0.01) during the follow-up period. However, day workers had a non-significant BMI gain. Using adjusted multiple linear regressions, we found that night workers had significantly larger BMI gain compared to day workers [B=0.89 (95% CI 0.06-1.72), P<0.05]. We did not find any significant association between average number of yearly night shifts and BMI change using our multiple linear regression model. Conclusions After adjusting for possible confounders, we found that BMI increased significantly more among night workers compared to day workers.

The Cognitive Mechanisms of the SNARC Effect: An Individual Differences Approach

PubMed Central

Viarouge, Arnaud; Hubbard, Edward M.; McCandliss, Bruce D.

2014-01-01

Access to mental representations of smaller vs. larger number symbols is associated with leftward vs. rightward spatial locations, as represented on a number line. The well-replicated SNARC effect (Spatial-Numerical Association of Response Codes) reveals that simple decisions about small numbers are facilitated when stimuli are presented on the left, and large numbers facilitated when on the right. We present novel evidence that the size of the SNARC effect is relatively stable within individuals over time. This enables us to take an individual differences approach to investigate how the SNARC effect is modulated by spatial and numerical cognition. Are number-space associations linked to spatial operations, such that those who have greater facility in spatial computations show the stronger SNARC effects, or are they linked to number semantics, such that those showing stronger influence of magnitude associations on number symbol decisions show stronger SNARC effects? Our results indicate a significant correlation between the SNARC effect and a 2D mental rotation task, suggesting that spatial operations are at play in the expression of this effect. We also uncover a significant correlation between the SNARC effect and the distance effect, suggesting that the SNARC is also related to access to number semantics. A multiple regression analysis reveals that the relative contributions of spatial cognition and distance effects represent significant, yet distinct, contributions in explaining variation in the size of the SNARC effect from one individual to the next. Overall, these results shed new light on how the spatial-numerical associations of response codes are influenced by both number semantics and spatial operations. PMID:24760048

Physical Activity, Energy Expenditure, Nutritional Habits, Quality of Sleep and Stress Levels in Shift-Working Health Care Personnel.

PubMed

Roskoden, Frederick Charles; Krüger, Janine; Vogt, Lena Johanna; Gärtner, Simone; Hannich, Hans Joachim; Steveling, Antje; Lerch, Markus M; Aghdassi, Ali A

2017-01-01

Among health care personnel working regular hours or rotating shifts can affect parameters of general health and nutrition. We have investigated physical activity, sleep quality, metabolic activity and stress levels in health care workers from both groups. We prospectively recruited 46 volunteer participants from the workforce of a University Medical Department of which 23 worked in rotating shifts (all nursing) and 21 non-shift regular hours (10 nursing, 13 clerical staff). All were investigated over 7 days by multisensory accelerometer (SenseWear Bodymedia® armband) and kept a detailed food diary. Physical activity and resting energy expenditure (REE) were measured in metabolic equivalents of task (METs). Quality of sleep was assessed as Pittsburgh Sleeping Quality Index and stress load using the Trier Inventory for Chronic Stress questionnaire (TICS). No significant differences were found for overall physical activity, steps per minute, time of exceeding the 3 METs level or sleep quality. A significant difference for physical activity during working hours was found between shift-workers vs. non-shift-workers (p<0.01) and for shift-working nurses (median = 2.1 METs SE = 0.1) vs. non-shift-working clerical personnel (median = 1.5 METs SE = 0.07, p<0.05). Non-shift-working nurses had a significantly lower REE than the other groups (p<0.05). The proportion of fat in the diet was significantly higher (p<0.05) in the office worker group (median = 42% SE = 1.2) whereas shift-working nurses consumed significantly more carbohydrates (median = 46% SE = 1.4) than clerical staff (median = 41% SE = 1.7). Stress assessment by TICS confirmed a significantly higher level of social overload in the shift working group (p<0.05). In this prospective cohort study shift-working had no influence on overall physical activity. Lower physical activity during working hours appears to be compensated for during off-hours. Differences in nutritional habits and stress load warrant larger scale trials to determine the effect on implicit health-associated conditions.

Physical Activity, Energy Expenditure, Nutritional Habits, Quality of Sleep and Stress Levels in Shift-Working Health Care Personnel

PubMed Central

Vogt, Lena Johanna; Gärtner, Simone; Hannich, Hans Joachim; Steveling, Antje; Lerch, Markus M.

2017-01-01

Background Among health care personnel working regular hours or rotating shifts can affect parameters of general health and nutrition. We have investigated physical activity, sleep quality, metabolic activity and stress levels in health care workers from both groups. Methods We prospectively recruited 46 volunteer participants from the workforce of a University Medical Department of which 23 worked in rotating shifts (all nursing) and 21 non-shift regular hours (10 nursing, 13 clerical staff). All were investigated over 7 days by multisensory accelerometer (SenseWear Bodymedia® armband) and kept a detailed food diary. Physical activity and resting energy expenditure (REE) were measured in metabolic equivalents of task (METs). Quality of sleep was assessed as Pittsburgh Sleeping Quality Index and stress load using the Trier Inventory for Chronic Stress questionnaire (TICS). Results No significant differences were found for overall physical activity, steps per minute, time of exceeding the 3 METs level or sleep quality. A significant difference for physical activity during working hours was found between shift-workers vs. non-shift-workers (p<0.01) and for shift-working nurses (median = 2.1 METs SE = 0.1) vs. non-shift-working clerical personnel (median = 1.5 METs SE = 0.07, p<0.05). Non-shift-working nurses had a significantly lower REE than the other groups (p<0.05). The proportion of fat in the diet was significantly higher (p<0.05) in the office worker group (median = 42% SE = 1.2) whereas shift-working nurses consumed significantly more carbohydrates (median = 46% SE = 1.4) than clerical staff (median = 41% SE = 1.7). Stress assessment by TICS confirmed a significantly higher level of social overload in the shift working group (p<0.05). Conclusion In this prospective cohort study shift-working had no influence on overall physical activity. Lower physical activity during working hours appears to be compensated for during off-hours. Differences in nutritional habits and stress load warrant larger scale trials to determine the effect on implicit health-associated conditions. PMID:28081231

Sleep and autonomic nervous system changes - enhanced cardiac sympathetic modulations during sleep in permanent night shift nurses.

PubMed

Chung, Min-Huey; Kuo, Terry B J; Hsu, Nanly; Chu, Hsin; Chou, Kuei-Ru; Yang, Cheryl C H

2009-05-01

Disturbed sleep is the most common problem among the many health-related effects of shift work, with shift workers clearly having higher rates of cardiac disorders. However, the possible mechanism underlying the related health effects of shift work has yet to be examined. Consequently, this study aimed to explore the influence of long-term night shift work on the sleep patterns of nurses and their cardiac autonomic nervous system during sleep. Our sample comprised ten permanent night shift and ten regular morning shift nurses. Nurses slept in their dormitory where they were allowed to sleep and wake spontaneously. All sleep parameters were digitized using an ambulatory polysomnographic recorder. Using sleep patterns and heart rate variability, the day- and nighttime sleep of permanent night shift nurses were compared with the nighttime sleep of regular morning shift nurses. Compared with the nighttime sleep of regular morning shift nurses, the pattern of daytime sleep of permanent night shift nurses showed significantly lower sleep onset latency. Permanent night shift nurses' daytime sleep also had greater proportions of Stage 3 and 4 (deep sleep), and arousal index than recorded during their nighttime sleep. Both the low frequency and low to high frequency ratio of the nighttime sleep of night shift nurses were significantly higher during periods of non-rapid eye movement (NREM) sleep than the nighttime sleep of morning shift workers. In addition, the electroencephalography delta-power of the nighttime sleep of night shift nurses was significantly lower during the first NREM episode sleep than those of both the daytime sleep of night shift workers and the nighttime sleep of morning shift nurses. Permanent night shift nurses have higher sympathetic activity during nighttime sleep than regular morning shift nurses. Night shift working may have effects on the sleeping patterns of nurses in the long run, inducing higher cardiac sympathetic regulation.

Neuroendocrine recovery after 2-week 12-h day and night shifts: an 11-day follow-up.

PubMed

Merkus, Suzanne L; Holte, Kari Anne; Huysmans, Maaike A; Hansen, Åse Marie; van de Ven, Peter M; van Mechelen, Willem; van der Beek, Allard J

2015-02-01

The study aimed to investigate the course and duration of neuroendocrine recovery after 2-week 12-h day and night shift working periods and to study whether there were differences in recovery between the shift groups. Twenty-nine male offshore employees working 2-week 12-h shift tours participated in the study; 15 participated after a day shift tour and 14 after a night shift tour. Salivary cortisol was assessed at awakening, 30 min after awakening, and before bedtime on the 1st, 4th, 7th, and 11th day of the free period, with a reference day prior to the offshore tour. Differences were tested using generalised estimating equations analysis. Compared to the reference day, night shift workers had a significantly flatter cortisol profile on the 1st day off, significantly lower cortisol concentrations at 30 min after awakening on day 4 and at awakening on day 7, and a significantly smaller decline to evening concentration on days 4 and 11. Compared to the reference day, day shift workers only showed a significantly lower cortisol concentration at awakening on the 1st day off. Compared to day workers, night shift workers had a flatter profile on the 1st day off and a lower cortisol concentration at awakening on the 4th day. Following 2-week 12-h night shift working periods, recovery was not fully complete up to day 11. Following 2-week 12-h day shift working periods, an indication of incomplete recovery was found on the 1st day off, with full recovery reached on day 4.

Sleep Quality Associated With Different Work Schedules: A Longitudinal Study of Nursing Staff.

PubMed

Niu, Shu-Fen; Miao, Nae-Fang; Liao, Yuan-Mei; Chi, Mei-Ju; Chung, Min-Huey; Chou, Kuei-Ru

2017-07-01

To explore the differences in sleep parameters between nurses working a slow, forward rotating shift and those working a fixed day shift. A longitudinal parallel-group comparison design was used in this prospective study. Participants (female) were randomly assigned to a rotating shift or a fixed day shift group. Participants in the rotating shift group worked day shift for the first 4 weeks, followed by evening shift for the second and night shift the third. Those in the day shift group worked day shift for all 12 weeks. Each kept a sleep diary and wore an actigraph (actigraph data were used to calculate total sleep time [TST], sleep onset latency [SOL], wake after sleep onset [WASO], and sleep efficiency [SE]) for 12 days, from Workday 1-4 in each of Weeks 4, 8, and 12. TST in nurses working evening rotating shift was higher than that for those working the day or night rotating shift and fixed day shift. WASO was significantly longer on Day 2 for rotating shift participants working evening versus day shift. SOL and SE were significantly shorter and lower in rotating shift nurses working night versus both day and evening shifts. A comprehensive understanding of the sleep patterns and quality of nurses with different work shifts may lead to better management of work shifts that reduces the influence of shift work on sleep quality.

Night shift work and levels of 6-sulfatoxymelatonin and cortisol in men.

PubMed

Mirick, Dana K; Bhatti, Parveen; Chen, Chu; Nordt, Frank; Stanczyk, Frank Z; Davis, Scott

2013-06-01

Night shift work is associated with cancer among men, but the biologic mechanism is unclear. We investigated whether male night shift workers showed changes in levels of melatonin and cortisol, potential biomarkers of cancer risk. Urine was collected from 185 night shift and 158 day shift-working male healthcare providers, aged 22 to 55 years, throughout work and sleep periods, and assayed for 6-sulfatoxymelatonin and cortisol. Morning serum was collected within 90 minutes of completing the night and assayed for cortisol. Night shift workers had significantly lower 6-sulfatoxymelatonin levels during daytime sleep, nighttime work, and nighttime sleep on off-nights (57%, 62%, and 40% lower, respectively), relative to the day shift workers during nighttime sleep (P < 0.0001); urinary cortisol in night shift workers was 16% higher during daytime sleep and 13% lower during nighttime sleep on off-nights (P < 0.05). Morning serum cortisol post-work and post-sleep in night shift workers were 24% and 43% lower, respectively, than post-sleep levels among day shift workers (P < 0.0001). Within-subject comparisons among the night shift workers revealed significantly lower melatonin levels and significantly higher urinary cortisol levels during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.01); morning serum cortisol levels post-work were lower than those post-sleep. Night shift workers have substantially lower 6-sulfatoxymelatonin during night work and daytime sleep, and levels remain low when night shift workers sleep at night. Chronic reduction in melatonin among night shift workers may be an important carcinogenic mechanism. Cortisol secretion patterns may be impacted by night shift work, which could affect cancer risk. Shift work could be an important risk factor for many types of cancer.

Extracellular Ca2+-induced force restoration in K+-depressed skeletal muscle of the mouse involves an elevation of [K+]i: implications for fatigue

PubMed Central

Leader, John P.; Loiselle, Denis S.; Higgins, Amanda; Lin, Wei; Renaud, Jean-Marc

2015-01-01

We examined whether a Ca2+-K+ interaction was a potential mechanism operating during fatigue with repeated tetani in isolated mouse muscles. Raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.3 to 10 mM in K+-depressed slow-twitch soleus and/or fast-twitch extensor digitorum longus muscles caused the following: 1) increase of intracellular K+ activity by 20–60 mM (raised intracellular K+ content, unchanged intracellular fluid volume), so that the K+-equilibrium potential increased by ∼10 mV and resting membrane potential repolarized by 5–10 mV; 2) large restoration of action potential amplitude (16–54 mV); 3) considerable recovery of excitable fibers (∼50% total); and 4) restoration of peak force with the peak tetanic force-extracellular K+ concentration ([K+]o) relationship shifting rightward toward higher [K+]o. Double-sigmoid curve-fitting to fatigue profiles (125 Hz for 500 ms, every second for 100 s) showed that prior exposure to raised [K+]o (7 mM) increased, whereas lowered [K+]o (2 mM) decreased, the rate and extent of force loss during the late phase of fatigue (second sigmoid) in soleus, hence implying a K+ dependence for late fatigue. Prior exposure to 10 mM [Ca2+]o slowed late fatigue in both muscle types, but was without effect on the extent of fatigue. These combined findings support our notion that a Ca2+-K+ interaction is plausible during severe fatigue in both muscle types. We speculate that a diminished transsarcolemmal K+ gradient and lowered [Ca2+]o contribute to late fatigue through reduced action potential amplitude and excitability. The raised [Ca2+]o-induced slowing of fatigue is likely to be mediated by a higher intracellular K+ activity, which prolongs the time before stimulation-induced K+ efflux depolarizes the sarcolemma sufficiently to interfere with action potentials. PMID:25571990

( sup 3 H)-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and ( sup 3 H) ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor

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

Branchek, T.; Adham, N.; Macchi, M.

1990-11-01

The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to (3H)ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding themore » serotonin 5-HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both (3H)DOB and (3H)ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5'-(beta, gamma-imido) triphosphate (Gpp(NH)p) to this system caused a rightward shift and steepening of agonist competition curves for (3H) ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity (3H)DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that (3H)DOB and (3H)ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein.« less

Integrative Conductance of Oxygen During Exercise at Altitude.

PubMed

Calbet, José A L; Lundby, Carsten; Boushel, Robert

2016-01-01

In the oxygen (O2) cascade downstream steps can never achieve higher flows of O2 than the preceding ones. At the lung the transfer of O2 is determined by the O2 gradient between the alveolar space and the lung capillaries and the O2 diffusing capacity (DLO2). While DLO2 may be increased several times during exercise by recruiting more lung capillaries and by increasing the oxygen carrying capacity of blood due to higher peripheral extraction of O2, the capacity to enhance the alveolocapillary PO2 gradient is more limited. The transfer of oxygen from the alveolar space to the hemoglobin (Hb) must overcome first the resistance offered by the alveolocapillary membrane (1/DM) and the capillary blood (1/θVc). The fractional contribution of each of these two components to DLO2 remains unknown. During exercise these resistances are reduced by the recruitment of lung capillaries. The factors that reduce the slope of the oxygen dissociation curve of the Hb (ODC) (i.e., lactic acidosis and hyperthermia) increase 1/θVc contributing to limit DLO2. These effects are accentuated in hypoxia. Reducing the size of the active muscle mass improves pulmonary gas exchange during exercise and reduces the rightward shift of the ODC. The flow of oxygen from the muscle capillaries to the mitochondria is pressumably limited by muscle O2 conductance (DmcO2) (an estimation of muscle oxygen diffusing capacity). However, during maximal whole body exercise in normoxia, a higher flow of O2 is achieved at the same pressure gradients after increasing blood [Hb], implying that in healthy humans exercising in normoxia there is a functional reserve in DmcO2. This conclusion is supported by the fact that during small muscle exercise in chronic hypoxia, peak exercise DmcO2 is similar to that observed during exercise in normoxia despite a markedly lower O2 pressure gradient driving diffusion.

Quantitative evaluation of human cerebellum-dependent motor learning through prism adaptation of hand-reaching movement.

PubMed

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the "adaptability index (AI)", which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions.

Fenoterol functionally activates the β₃-adrenoceptor in human urinary bladder, comparison with rat and mouse: implications for drug discovery.

PubMed

Palea, Stefano; Rekik, Moèz; Rouget, Céline; Camparo, Philippe; Botto, Henri; Rischmann, Pascal; Lluel, Philippe; Westfall, Timothy D

2012-09-05

Fenoterol has been reported to be a potent and selective β(2)-adrenoceptor agonist and is currently used clinically to treat asthma. Electrical field stimulation (EFS) of isolated urinary bladder mimics the voiding contraction by stimulating parasympathetic nerves, resulting in neurogenic contractions. To determine if stimulation of β(2)-adrenoceptors can inhibit this response, fenoterol was tested against EFS-induced contractions in human isolated urinary bladder and compared with mouse and rat. Bladder strips were mounted in organ baths and reproducible contractions induced by EFS. Fenoterol was added cumulatively in the presence of the β(2)-adrenoceptor antagonist ICI118551 or the β(3)-adrenoceptor antagonist L-748337. Fenoterol inhibited neurogenic contractions in all three species in a concentration-dependent manner with pEC(50) values of 6.66 ± 0.11, 6.86 ± 0.06 and 5.71 ± 0.1 in human, mouse and rat respectively. In human bladder strips ICI118551 (100 nM) did not affect responses to fenoterol, while L-748337 (0.3-3 μM) produced rightward shifts of the concentration-response curves with a pA(2) value of 8.10. In mouse bladder strips ICI118551 (30 nM) blocked the inhibitory effect of fenoterol (pA(2)=8.80), while L-748337 (10 μM) inhibited the response with a pA(2) of 5.79. In rat bladder ICI118551 (30 nM) was without effect, while L-748,337 (10 μM) inhibited the response to fenoterol with a pA(2) of 5.40. From these results it is clear that fenoterol potently activates β(3)-adrenoceptors in human isolated urinary bladder to inhibit EFS-induced contractions. Fenoterol also activates β(3)-adrenoceptors in rat, but β(2)-adrenoceptors in mouse bladder to inhibit EFS-induced contractions. Copyright © 2012 Elsevier B.V. All rights reserved.

Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

PubMed

Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

2016-06-02

Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Sodium Carbonate is Saltier Than Sodium Chloride to Sodium-Depleted Rats.

PubMed

St John, Steven J; McBrayer, Anya M; Krauskopf, Erin E

2017-10-01

In a series of behavioral experiments in the 1960s, G.R. Morrison identified several unique features of the taste of Na2CO3 to rats; namely, it is 1) considerably more intense than NaCl at isomolar concentrations, 2) avoided at 10 times lower concentrations than NaCl to thirsty rats, 3) preferred at 10 times lower concentrations than NaCl in sodium-depleted rats. He also demonstrated its qualitatively similarity to NaCl. In Experiment 1, we confirmed and extended many of Morrison's observations. Rats were injected with furosemide on 3 occasions to stimulate a sodium appetite. After each depletion, rats were given a brief-access taste test in a lickometer presenting, in random order, water and 7 concentrations of salt. One test used NaCl (0.028-0.89 M, quarter log steps), another used Na2CO3, and the third used Na2CO3, but at a tenfold lower concentration range (0.0028-0.089 M). Rats licked NaCl in an inverted-U shaped concentration-response function peaking at 0.158-0.281 M. As Morrison's results predicted, rats licked Na2CO3 in nearly identical fashion, but at a tenfold lower concentration range (peak at 0.0158-0.028 M). In a second experiment, furosemide-treated rats were repeatedly tested with the lower Na2CO3 range but mixed in the epithelial sodium channel blocker amiloride at various concentrations (3-300 μM, half log steps). Amiloride reduced licking for Na2CO3 and shifted the peak response rightward up to about half a log unit. Thus, this "super-saltiness" of Na2CO3 to rats is at least partly amiloride-dependent. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of [D-Phe6] bombesin (6-13) methylester, a bombesin receptor antagonist, towards bombesin-induced contractions in the guinea-pig and rat isolated urinary bladder.

PubMed

Maggi, C A; Coy, D H; Giuliani, S

1992-08-01

1. The effect of [D-Phe6] bombesin (6-13) methylester (OMe), a newly developed potent antagonist of bombesin receptors, has been investigated against bombesin-induced contractions of the guinea-pig and rat isolated urinary bladder. 2. Bombesin (0.1 nM-10 microM) produced a concentration-dependent contraction of the guinea-pig isolated bladder which approached the same maximum response as KCl (80 mM). The response to bombesin was antagonized in a competitive manner (rightward shift of the concentration-response curve without depression of the maximal response) by [D-Phe6] bombesin (6-13) OMe (0.3-10 microM). Degree of antagonism was concentration-dependent between 0.3 and 3 microM (dose ratios = 2.4, 9 and 39 in the presence of 0.3, 1, 3 microM of the antagonist). However, a larger concentration (10 microM) of the antagonist was not more effective (dose ratio = 36) than 3 microM. 3. Neither the action of bombesin nor the activity of the antagonist was influenced by peptidase inhibitors (bestatin, captopril and thiorphan 3 microM each) or by atropine, indomethacin, chlorpheniramine and desensitization of P2x purinoceptors by alpha, beta methylene ATP. 4. The bombesin antagonist was ineffective against contraction of the guinea-pig urinary bladder produced by the NK-1 tachykinin receptor-selective agonist, [Sar9] substance P sulphone. The action of the NK-1 receptor agonist was antagonized by L 668, 169 (3 microM), a cyclic peptide tachykinin antagonist. L 668, 169 had no effect toward bombesin-induced contraction. 5. The bombesin antagonist (1-10 microM) had no effect against the non-adrenergic non-cholinergic response of the guinea-pig isolated urinary bladder to electrical field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of kinin receptors modulating neurogenic contractions of the mouse isolated vas deferens.

PubMed Central

Maas, J; Rae, G A; Huidobro-Toro, J P; Calixto, J B

1995-01-01

1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7606350

Effect of PEEP, blood volume, and inspiratory hold maneuvers on venous return.

PubMed

Berger, David; Moller, Per W; Weber, Alberto; Bloch, Andreas; Bloechlinger, Stefan; Haenggi, Matthias; Sondergaard, Soren; Jakob, Stephan M; Magder, Sheldon; Takala, Jukka

2016-09-01

According to Guyton's model of circulation, mean systemic filling pressure (MSFP), right atrial pressure (RAP), and resistance to venous return (RVR) determine venous return. MSFP has been estimated from inspiratory hold-induced changes in RAP and blood flow. We studied the effect of positive end-expiratory pressure (PEEP) and blood volume on venous return and MSFP in pigs. MSFP was measured by balloon occlusion of the right atrium (MSFPRAO), and the MSFP obtained via extrapolation of pressure-flow relationships with airway occlusion (MSFPinsp_hold) was extrapolated from RAP/pulmonary artery flow (QPA) relationships during inspiratory holds at PEEP 5 and 10 cmH2O, after bleeding, and in hypervolemia. MSFPRAO increased with PEEP [PEEP 5, 12.9 (SD 2.5) mmHg; PEEP 10, 14.0 (SD 2.6) mmHg, P = 0.002] without change in QPA [2.75 (SD 0.43) vs. 2.56 (SD 0.45) l/min, P = 0.094]. MSFPRAO decreased after bleeding and increased in hypervolemia [10.8 (SD 2.2) and 16.4 (SD 3.0) mmHg, respectively, P < 0.001], with parallel changes in QPA Neither PEEP nor volume state altered RVR (P = 0.489). MSFPinsp_hold overestimated MSFPRAO [16.5 (SD 5.8) vs. 13.6 (SD 3.2) mmHg, P = 0.001; mean difference 3.0 (SD 5.1) mmHg]. Inspiratory holds shifted the RAP/QPA relationship rightward in euvolemia because inferior vena cava flow (QIVC) recovered early after an inspiratory hold nadir. The QIVC nadir was lowest after bleeding [36% (SD 24%) of preinspiratory hold at 15 cmH2O inspiratory pressure], and the QIVC recovery was most complete at the lowest inspiratory pressures independent of volume state [range from 80% (SD 7%) after bleeding to 103% (SD 8%) at PEEP 10 cmH2O of QIVC before inspiratory hold]. The QIVC recovery thus defends venous return, possibly via hepatosplanchnic vascular waterfall. Copyright © 2016 the American Physiological Society.

Multisensory and Modality-Specific Influences on Adaptation to Optical Prisms

PubMed Central

Calzolari, Elena; Albini, Federica; Bolognini, Nadia; Vallar, Giuseppe

2017-01-01

Visuo-motor adaptation to optical prisms displacing the visual scene (prism adaptation, PA) is a method used for investigating visuo-motor plasticity in healthy individuals and, in clinical settings, for the rehabilitation of unilateral spatial neglect. In the standard paradigm, the adaptation phase involves repeated pointings to visual targets, while wearing optical prisms displacing the visual scene laterally. Here we explored differences in PA, and its aftereffects (AEs), as related to the sensory modality of the target. Visual, auditory, and multisensory – audio-visual – targets in the adaptation phase were used, while participants wore prisms displacing the visual field rightward by 10°. Proprioceptive, visual, visual-proprioceptive, auditory-proprioceptive straight-ahead shifts were measured. Pointing to auditory and to audio-visual targets in the adaptation phase produces proprioceptive, visual-proprioceptive, and auditory-proprioceptive AEs, as the typical visual targets did. This finding reveals that cross-modal plasticity effects involve both the auditory and the visual modality, and their interactions (Experiment 1). Even a shortened PA phase, requiring only 24 pointings to visual and audio-visual targets (Experiment 2), is sufficient to bring about AEs, as compared to the standard 92-pointings procedure. Finally, pointings to auditory targets cause AEs, although PA with a reduced number of pointings (24) to auditory targets brings about smaller AEs, as compared to the 92-pointings procedure (Experiment 3). Together, results from the three experiments extend to the auditory modality the sensorimotor plasticity underlying the typical AEs produced by PA to visual targets. Importantly, PA to auditory targets appears characterized by less accurate pointings and error correction, suggesting that the auditory component of the PA process may be less central to the building up of the AEs, than the sensorimotor pointing activity per se. These findings highlight both the effectiveness of a reduced number of pointings for bringing about AEs, and the possibility of inducing PA with auditory targets, which may be used as a compensatory route in patients with visual deficits. PMID:29213233

Quantitative Evaluation of Human Cerebellum-Dependent Motor Learning through Prism Adaptation of Hand-Reaching Movement

PubMed Central

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the “adaptability index (AI)”, which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions. PMID:25785588

Skin grafting impairs postsynaptic cutaneous vasodilator and sweating responses.

PubMed

Davis, Scott L; Shibasaki, Manabu; Low, David A; Cui, Jian; Keller, David M; Purdue, Gary F; Hunt, John L; Arnoldo, Brett D; Kowalske, Karen J; Crandall, Craig G

2007-01-01

This study tested the hypothesis that postsynaptic cutaneous vascular responses to endothelial-dependent and -independent vasodilators, as well as sweat gland function, are impaired in split-thickness grafted skin 5 to 9 months after surgery. Intradermal microdialysis membranes were placed in grafted and adjacent control skin, thereby allowing local delivery of the endothelial-dependent vasodilator, acetylcholine (ACh; 1 x 10(-7) to 1 x 10(-1) M at 10-fold increments) and the endothelial-independent nitric oxide donor, sodium nitroprusside (SNP; 5 x 10(-8) to 5 x 10(-2) M at 10-fold increments). Skin blood flow and sweat rate were simultaneously assessed over the semipermeable portion of the membrane. Cutaneous vascular conductance (CVC) was calculated from the ratio of laser Doppler-derived skin blood flow to mean arterial blood pressure. deltaCVC responses from baseline to these drugs were modeled via nonlinear regression curve fitting to identify the dose of ACh and SNP causing 50% of the maximal vasodilator response (EC50). A rightward shift in the CVC dose response curve for ACh was observed in grafted (EC50 = -2.61 +/- 0.44 log M) compared to adjacent control skin (EC50 = -3.34 +/- 0.46 log M; P = .003), whereas the mean EC50 for SNP was similar between grafted (EC50 = -4.21 +/- 0.94 log M) and adjacent control skin (EC50 = -3.87 +/- 0.65 log M; P = 0.332). Only minimal sweating to exogenous ACh was observed in grafted skin whereas normal sweating was observed in control skin. Increased EC50 and decreased maximal CVC responses to the exogenous administration of ACh suggest impairment of endothelial-dependent cutaneous vasodilator responses in grafted skin 5 to 9 months after surgery. Greatly attenuated sweating responses to ACh suggests either abnormal or an absence of functional sweat glands in the grafted skin.

Role of inhibition in the specification of orientation selectivity of cells in the cat striate cortex.

PubMed

Bonds, A B

1989-01-01

Mechanisms supporting orientation selectivity of cat striate cortical cells were studied by stimulation with two superimposed sine-wave gratings of different orientations. One grating (base) generated a discharge of known amplitude which could be modified by the second grating (mask). Masks presented at nonoptimal orientations usually reduced the base-generated response, but the degree of reduction varied widely between cells. Cells with narrow orientation tuning tended to be more susceptible to mask presence than broadly tuned cells; similarly, simple cells generally showed more response reduction than did complex cells. The base and mask stimuli were drifted at different temporal frequencies which, in simple cells, permitted the identification of individual response components from each stimulus. This revealed that the reduction of the base response by the mask usually did not vary regularly with mask orientation, although response facilitation from the mask was orientation selective. In some sharply tuned simple cells, response reduction had clear local maxima near the limits of the cell's orientation-tuning function. Response reduction resulted from a nearly pure rightward shift of the response versus log contrast function. The lowest mask contrast yielding reduction was within 0.1-0.3 log unit of the lowest contrast effective for excitation. The temporal-frequency bandpass of the response-reduction mechanism resembled that of most cortical cells. The spatial-frequency bandpass was much broader than is typical for single cortical cells, spanning essentially the entire visual range of the cat. These findings are compatible with a model in which weak intrinsic orientation-selective excitation is enhanced in two stages: (1) control of threshold by nonorientation-selective inhibition that is continuously dependent on stimulus contrast; and (2) in the more narrowly tuned cells, orientation-selective inhibition that has local maxima serving to increase the slope of the orientation-tuning function.

A cell-based assay to assess the persistence of action of agonists acting at recombinant human beta(2) adrenoceptors.

PubMed

Summerhill, Susan; Stroud, Timothy; Nagendra, Roshini; Perros-Huguet, Christelle; Trevethick, Michael

2008-01-01

The aim was to establish a robust, 96-well, cell-based assay to assess the potency and persistence of action of agonists acting at human recombinant beta(2) adrenoceptors expressed in CHO (Chinese Hamster Ovary) cells and to compare this with published duration of action data in guinea pig isolated trachea and human bronchus. Cells were treated with either: (i) beta-adrenoceptor agonist for 30 min, washed and cyclicAMP (cAMP) measured 30 min later-termed 'washed' cells or, (ii) treated with solvent for 30 min, washed, and then treated with beta-adrenoceptor agonist for 30 min and cAMP measured-termed 'unwashed' cells. The 'washed' EC(50) was divided by the 'unwashed' EC(50) to determine a rightward shift concentration ratio, which was indicative of the persistence of action at the receptor. At the beta(2) adrenoceptor salmeterol, carmoterol and indacaterol were resistant to washing with a concentration ratio of <5, indicating a long persistence of action, whereas formoterol, isoprenaline and salbutamol were washed out with a ratio of 32, >294 and >800 respectively, suggesting a shorter persistence of action. At beta(1) and beta(3) adrenoceptors all compounds washed out. The persistent effects of salmeterol at beta(2) following washing could be reversed by the selective beta(2) antagonist ICI 118551, suggesting continued receptor activation. The data presented agree well with published data assessing duration of action of beta(2) agonists in human isolated bronchus and guinea pig isolated trachea. Key features are: (a) it is a 96-well format which can be used to assess many compounds in a single experiment, (b) both potency and persistence of agonist action are assessed in the same assay, (c) any effects of concentration on the persistence of action can be highlighted, and (d) it allows triage of compounds prior to tissue bath studies thus reducing the use of animal tissue.

Protons inhibit anoctamin 1 by competing with calcium.

PubMed

Chun, Hyeyeon; Cho, Hawon; Choi, Jimi; Lee, Jesun; Kim, Sung Min; Kim, Hyungsup; Oh, Uhtaek

2015-11-01

Cl(-) efflux through Ca(2+)-activated Cl(-) channels (CaCCs) in secretory epithelial cells plays a key role in the regulation of fluid secretion. The fluid and electrolyte secretion is closely related to intracellular pH. CaCCs have been known to be inhibited by intracellular acid. However, the molecular mechanism for the inhibition remains unknown. Anoctamin 1 (ANO1) is a Ca(2+)-activated Cl(-) channel that mediates numerous physiological functions including fluid secretion in secretory epithelia. However, little is known about whether ANO1 can be modulated by change of intracellular pH. Here, we demonstrate that Ca(2+)-induced activation of ANO1 and its homolog ANO2 are strongly inhibited by intracellular acid. Intracellular acid caused a rightward shift of the concentration-response curve of Ca(2+) in activating ANO1 and ANO2. To identify the location of the acid-induced inhibition, mutations were made on each of all histidine residues in cytoplasmic part of ANO1. However, none of the His-mutant showed the reduction in the acid-induced inhibition. Furthermore, mutation on Glu- or Asp-residues in the multiple acidic-amino acid regions was ineffective in blocking the acid-induced inhibition. Because the Ca(2+)-binding site of a fungal anoctamin (nhTMEM16) was uncovered by crystallography, mutagenesis was performed in this region. Surprisingly, mutations at Glu, Asp or Asn residues in the hydrophobic core that are known to be essential for Ca(2+)-induced activation of ANO1 blocked the acid-induced inhibition. These results suggest that protons interfere with Ca(2+) at the Ca(2+) binding site of ANO1. These findings provide a molecular mechanism underlying the acid-induced inhibition of ANO1, which may contribute to control fluid and electrolyte secretion in the secretory epithelia. Copyright © 2015. Published by Elsevier Ltd.

Hypoxia and alkalinization inhibit endothelium-derived nitric oxide but not endothelium-derived hyperpolarizing factor responses in porcine coronary artery.

PubMed

Shimizu, S; Paul, R J

1999-10-01

We investigated the mechanisms by which hypoxia and alkalinization inhibit the endothelium-dependent relaxation to Substance P (SP) in porcine coronary artery. In a KCl contracture, the major component of the SP response is endothelium-derived nitric oxide (EDNO), whereas with receptor-mediated 9,11-dideoxy-llalpha, 9alpha-epoxymethanoprostaglandin F(2alpha) (U46619) stimulation, the SP response is dependent on both EDNO and endothelium-derived hyperpolarization factor. Intracellular alkalinization by NH(4)Cl reduced the peak of SP responses when arteries were contracted with KCl, whereas with U46619 stimulation, the peak was little effected but the duration was shortened. In endothelial cell-denuded arteries, alkalinization with NH(4)Cl shifted the sodium nitroprusside concentration-relaxation relations rightward. The effects of NH(4)Cl in SP- and sodium nitroprusside-induced relaxations were attenuated by decreasing extracellular pH (pH(o)) from 7.4 to 7.2, which normalized intracellular pH (pH(i)) to control levels. In contrast, in U46619 contractures, the SP response in the presence of a NO synthase inhibitor was unaffected by NH(4)Cl. Moreover, hypoxia blunted but did not abolish the responses to SP for U46619 contractures; addition of KCl, however, abolished the SP response under hypoxia. Endothelial [Ca(2+)](i) was measured with fura-2 differentially loaded only into endothelial cells on intact arteries. Despite the attenuation of the SP response in KCl contractures by NH(4)Cl or hypoxia, endothelial [Ca(2+)](i) responses were unchanged. Our results suggest that hypoxia and alkalinization inhibit EDNO but not endothelium-derived hyperpolarization factor relaxations through a mechanism(s) not involving endothelial cell [Ca(2+)](i). Inhibition of EDNO relaxation by alkalinization with NH(4)Cl is likely to occur at the level of activation of guanylate cyclase and/or at a step downstream in smooth muscle.

Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure

PubMed Central

Hutsell, Blake A.; Blough, Bruce E.; Poklis, Justin L.; Negus, S. Stevens

2015-01-01

Background: Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment’s efficacy in decreasing cocaine consumption is unknown. Methods: This study compared lisdexamfetamine and d-amphetamine effects in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus-food choice self-administration procedure. Results: In the cocaine-discrimination procedure, lisdexamfetamine (0.32–3.2mg/kg, i.m.) substituted for cocaine with lower potency, slower onset, and longer duration of action than d-amphetamine (0.032–0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In the choice procedure, cocaine (0–0.1mg/kg/injection, i.v.) and food (1g banana-flavored pellets) were concurrently available, and cocaine maintained a dose-dependent increase in cocaine choice under baseline conditions. Treatment for 7 consecutive days with lisdexamfetamine (0.32–3.2mg/kg/day, i.m.) or d-amphetamine (0.032–0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection cocaine. Conclusions: Lisdexamfetamine has a slower onset and longer duration of action than amphetamine but retains amphetamine’s efficacy to reduce the choice of cocaine in rhesus monkeys. These results support further consideration of lisdexamfetamine as an agonist-based medication candidate for cocaine addiction. PMID:25618405

Association between depressive symptoms and morningness-eveningness, sleep duration and rotating shift work in Japanese nurses.

PubMed

Togo, Fumiharu; Yoshizaki, Takahiro; Komatsu, Taiki

2017-01-01

Higher depressive symptoms have been reported in rotating shift workers compared with day workers. Depressive symptoms in adults who do not engage in night work have also been shown to be associated with chronotype and sleep duration. This study examines associations between depressive symptoms, morningness-eveningness (i.e. the degree to which people prefer to be active in the morning or the evening), sleep duration and rotating shift work. Japanese nurses (1252 day workers and 1780 rotating shift workers, aged 20-59) were studied using a self-administered questionnaire. The questionnaire covered depressive symptoms, morningness-eveningness, sleep habits and demographic characteristics of the participants. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to determine the levels of depressive symptoms. A Japanese version of the Morningness-Eveningness Questionnaire (MEQ) was used to measure morningness-eveningness. The CES-D score of shift workers was significantly (p < 0.05) higher than that of day workers. The MEQ score was significantly (p < 0.05) lower (i.e. greater eveningness) in shift workers than in day workers. Sleep duration on the day shift was significantly (p < 0.05) shorter in shift workers than in day workers. Simple linear regression revealed that the MEQ score, sleep duration on the day shift and current work shift (i.e. rotating shift work) were significantly (p < 0.05) associated with the CES-D score. Multivariate linear regression indicated that greater eveningness and shorter sleep duration were independently associated with higher CES-D scores, while rotating shift work was not. These associations between the MEQ score, the sleep duration and the CES-D score were also confirmed in both day workers and shift workers when the groups were analyzed separately. These results suggest that greater eveningness and shorter sleep duration on the day shift were independently associated with higher levels of depressive symptoms, which may explain associations between rotating shift workers and depressive symptoms. These findings have important implications for the development of novel strategies for preventing poor mental health in day workers and rotating shift workers.

The influence of shift work on cognitive functions and oxidative stress.

PubMed

Özdemir, Pınar Güzel; Selvi, Yavuz; Özkol, Halil; Aydın, Adem; Tülüce, Yasin; Boysan, Murat; Beşiroğlu, Lütfullah

2013-12-30

Shift work influences health, performance, activity, and social relationships, and it causes impairment in cognitive functions. In this study, we investigated the effects of shift work on participants' cognitive functions in terms of memory, attention, and learning, and we measured the effects on oxidative stress. Additionally, we investigated whether there were significant relationships between cognitive functions and whole blood oxidant/antioxidant status of participants. A total of 90 health care workers participated in the study, of whom 45 subjects were night-shift workers. Neuropsychological tests were administered to the participants to assess cognitive function, and blood samples were taken to detect total antioxidant capacity and total oxidant status at 08:00. Differences in anxiety, depression, and chronotype characteristics between shift work groups were not significant. Shift workers achieved significantly lower scores on verbal memory, attention-concentration, and the digit span forward sub-scales of the Wechsler Memory Scale-Revised (WMS-R), as well as on the immediate memory and total learning sub-scales of the Auditory Verbal Learning Test (AVLT). Oxidative stress parameters were significantly associated with some types of cognitive function, including attention-concentration, recognition, and long-term memory. These findings suggest that night shift work may result in significantly poorer cognitive performance, particularly working memory. © 2013 Elsevier Ireland Ltd. All rights reserved.

[Analysis of relationship between shift-work and occupational stress among workers from different companies].

PubMed

Gu, Guizhen; Yu, Shanfa; Zhou, Wenhui; Wu, Hui

2016-01-01

To investigate the relationship between work in shifts and occupational stress. A total of 5338 employees from 13 companies were investigated by cluster sampling, and occupational stress measuring tools, job content questionnaire, and effort-reward imbalance questionnaire were used to investigate occupational stress factors, stress reaction, and the condition of work in shifts. The employees who worked in shifts accounted for 46.6%. The condition of work in shifts varied significantly across different companies, employees with different individual features (including sex, job title, degree of education, age, working years, smoking, and drinking), and employees with different weekly working times(P<0.01 or P<0.05); health status was associated with work in shifts(P<0.01); compared with the employees who did not work in shifts, those who worked in shifts had significantly lower scores of technology utilization, work control level, psychological need, reward, social support, and job satisfaction(P<0.01 or P<0.05), as well as significantly higher scores of physical demands, effort, depressive symptoms, and negative affectivity(P<0.01). Work in shifts can affect health status, and is associated with occupational stress.

Anticipation by basketball defenders: an explanation based on the three-dimensional inverted pendulum model.

PubMed

Fujii, Keisuke; Shinya, Masahiro; Yamashita, Daichi; Kouzaki, Motoki; Oda, Shingo

2014-01-01

We previously estimated the timing when ball game defenders detect relevant information through visual input for reacting to an attacker's running direction after a cutting manoeuvre, called cue timing. The purpose of this study was to investigate what specific information is relevant for defenders, and how defenders process this information to decide on their opponents' running direction. In this study, we hypothesised that defenders extract information regarding the position and velocity of the attackers' centre of mass (CoM) and the contact foot. We used a model which simulates the future trajectory of the opponent's CoM based upon an inverted pendulum movement. The hypothesis was tested by comparing observed defender's cue timing, model-estimated cue timing using the inverted pendulum model (IPM cue timing) and cue timing using only the current CoM position (CoM cue timing). The IPM cue timing was defined as the time when the simulated pendulum falls leftward or rightward given the initial values for position and velocity of the CoM and the contact foot at the time. The model-estimated IPM cue timing and the empirically observed defender's cue timing were comparable in median value and were significantly correlated, whereas the CoM cue timing was significantly more delayed than the IPM and the defender's cue timings. Based on these results, we discuss the possibility that defenders may be able to anticipate the future direction of an attacker by forwardly simulating inverted pendulum movement.

The effect of sex and handedness on white matter anisotropy: a diffusion tensor magnetic resonance imaging study.

PubMed

Powell, J L; Parkes, L; Kemp, G J; Sluming, V; Barrick, T R; García-Fiñana, M

2012-04-05

Diffusion tensor magnetic resonance imaging provides a way of assessing the asymmetry of white matter (WM) connectivity, the degree of anisotropic diffusion within a given voxel being a marker of coherently bundled myelinated fibers. Voxel-based statistical analysis was performed on fractional anisotropy (FA) images of 42 right- and 40 left-handers, to assess differences in underlying WM anisotropy and FA asymmetry across the whole brain. Right-handers show greater anisotropy than left-handers in the uncinate fasciculus (UF) within the limbic lobe, and WM underlying prefrontal cortex, medial and inferior frontal gyri. Significantly greater leftward FA asymmetry in cerebellum posterior lobe is seen in left- than right-handers, and males show significantly greater rightward (right-greater-than-left) FA asymmetry in regions of middle occipital lobe, medial temporal gyrus, and a region of the superior longitudinal fasciculus underlying the supramarginal gyrus. Leftward (left-greater-than-right) anisotropy is found in regions of the arcuate fasciculus (AF), UF, and WM underlying pars triangularis in both handedness groups, with right-handers alone showing additional leftward FA asymmetry along the length of the superior temporal gyrus. Overall results indicate that although both handedness groups show anisotropy in similar WM regions, greater anisotropy is observed in right-handers compared with left-handers. The largest differences in FA asymmetry are found between males and females, suggesting a greater effect of sex than handedness on FA asymmetry. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

The influence of sex chromosome aneuploidy on brain asymmetry.

PubMed

Rezaie, Roozbeh; Daly, Eileen M; Cutter, William J; Murphy, Declan G M; Robertson, Dene M W; DeLisi, Lynn E; Mackay, Clare E; Barrick, Thomas R; Crow, Timothy J; Roberts, Neil

2009-01-05

The cognitive deficits present in individuals with sex chromosome aneuploidies suggest that hemispheric differentiation of function is determined by an X-Y homologous gene [Crow (1993); Lancet 342:594-598]. In particular, females with Turner's syndrome (TS) who have only one X-chromosome exhibit deficits of spatial ability whereas males with Klinefelter's syndrome (KS) who possess a supernumerary X-chromosome are delayed in acquiring words. Since spatial and verbal abilities are generally associated with right and left hemispheric function, such deficits may relate to anomalies of cerebral asymmetry. We therefore applied a novel image analysis technique to investigate the relationship between sex chromosome dosage and structural brain asymmetry. Specifically, we tested Crow's prediction that the magnitude of the brain torque (i.e., a combination of rightward frontal and leftward occipital asymmetry) would, as a function of sex chromosome dosage, be respectively decreased in TS women and increased in KS men, relative to genotypically normal controls. We found that brain torque was not significantly different in TS women and KS men, in comparison to controls. However, TS women exhibited significantly increased leftward brain asymmetry, restricted to the posterior of the brain and focused on the superior temporal and parietal-occipital association cortex, while KS men showed a trend for decreased brain asymmetry throughout the frontal lobes. The findings suggest that the number of sex chromosomes influences the development of brain asymmetry not simply to modify the torque but in a complex pattern along the antero-posterior axis. 2008 Wiley-Liss, Inc.

Normative data on angular vestibulo-ocular responses in the yaw axis measured using the video head impulse test.

PubMed

Matiño-Soler, Eusebi; Esteller-More, Eduard; Martin-Sanchez, Juan-Carlos; Martinez-Sanchez, Jose-M; Perez-Fernandez, Nicolas

2015-03-01

To analyze vestibulo-ocular responses using the video head impulse test in the yaw axis. Prospective. Tertiary and university hospital. Two hundred twelve healthy subjects with no history of vestibular or neurologic impairment. Video head impulse test in the lateral semicircular canal plane. Vestibulo-ocular reflex (VOR) gain and appearance of refixation saccades (RSs) considering sex, age, and head impulse velocity and direction. Mean gain was 1.06 ± 0.07, and there were no differences between sexes. For all the impulses (n = 9,654; 4,947 rightward and 4,707 leftward), VOR gain decreased as head impulse velocity increased. When gain was evaluated by age and head velocity, it was steady until age 70 years for higher-velocity impulses and until age 90 years for lower-velocity head impulses. RSs were detected in 52 subjects, occurring after impulses to both sides of the head in 22 of these subjects. The number of subjects with RSs was significantly higher after age 71 years, and velocity was correlated, not with age, but with head impulse velocity. VOR gain was stable until age 90 years and thereafter dropped. However, this decrease occurred progressively in younger subjects as head impulse velocity increased, with VOR gain for faster head impulses decreasing significantly in subjects older than 70 years. This finding, in addition to the appearance of RSs, can be explained by the effect of aging on the deterioration of the vestibular system in the semicircular canals.

Comparative Study of Job Burnout Among Critical Care Nurses With Fixed and Rotating Shift Schedules

PubMed Central

Shamali, Mahdi; Shahriari, Mohsen; Babaii, Atye; Abbasinia, Mohammad

2015-01-01

Background: Nurses, as health care providers, are insurmountably obliged to the practice of shift work. Literature has reported shift working as one of the inducing factors of burnout. Despite numerous studies in this area, there are inconsistencies on the relationship between shift working and burnout among nurses, especially in those who work in critical care settings. Objectives: The aim of this study was to compare the occupational burnout in critical care nurses with and without fixed shift schedules. Patients and Methods: In this comparative study, 130 nurses with rotating shift schedule and 130 nurses with fixed shift schedule from six university hospitals were selected using stratified random sampling. Maslach burnout inventory was used for data collection. Independent samples t-test, chi-square and one-way ANOVA tests were used to analyze the data. Results: Most of the participants were females (62.7%), aged between 22 - 29 years (38.5%), married (59.2%), and had a bachelor degree (86.9%). The mean score of emotional exhaustion was significantly higher in nurses with fixed shift schedules (P < 0.001). However, no significant difference was found between the mean scores of the two groups in the personal accomplishment and depersonalization subscales (P > 0.05). Moreover, no significant difference was found in burnout mean scores between nurses with fixed morning and fixed night shifts (P > 0.05). The means of the emotional exhaustion subscale were significantly different in nurses with different characteristics (P < 0.05) except the gender and working unit. Conclusions: As a result of this study, it was found that critical care nurses with fixed shift schedules display more burnout in emotional exhaustion dimension, compared to those working with rotating shift schedules. PMID:26576442

[The growth movements of moss protonemata under clinostatic and microgravity conditions

NASA Technical Reports Server (NTRS)

Demkiv, O. T.; Kordium, E. L.; Tairbekov, M. G.; Sack, F.; Kern, F.; Kardash, A. R.

1999-01-01

Populations of dark-grown protonemata of moss Ceratodon purpureus wt-4 (Germany) and wt-U (Ukraine) were rotated on clinostat or flown in space (experiment "Protonema" aboard Bion-11, December 24, 1996-January 7, 1997) to determine the effects of altered gravity on orientation of protonemata growing filaments. Protonemata had been cultivated 8 days in vertical stationary position at dark to be transported to microgravity or placed in clinostat for the period of 14 days. In the ground control, protonemata demonstrated the negatively gravitropic growth (straight upwards in a bundle of compact filaments). The horizontal or circular rotation in clinostat and exposure to microgravity made filaments grow every each way within the substrate plane but with an apparent trend to rightward curling resulting in "spiral galaxies".

Time in the eye of the beholder: Gaze position reveals spatial-temporal associations during encoding and memory retrieval of future and past.

PubMed

Martarelli, Corinna S; Mast, Fred W; Hartmann, Matthias

2017-01-01

Time is grounded in various ways, and previous studies point to a "mental time line" with past associated with the left, and future with the right side. In this study, we investigated whether spontaneous eye movements on a blank screen would follow a mental timeline during encoding, free recall, and recognition of past and future items. In all three stages of processing, gaze position was more rightward during future items compared to past items. Moreover, horizontal gaze position during encoding predicted horizontal gaze position during free recall and recognition. We conclude that mental time line and the stored gaze position during encoding assist memory retrieval of past versus future items. Our findings highlight the spatial nature of temporal representations.

The costs of hemispheric specialization in a fish

PubMed Central

Dadda, Marco; Zandonà, Eugenia; Agrillo, Christian; Bisazza, Angelo

2009-01-01

Laboratory and field studies have documented better cognitive performance associated with marked hemispheric specialization in organisms as diverse as chimpanzees, domestic chicks and topminnows. While providing an evolutionary explanation for the emergence of cerebral lateralization, this evidence represents a paradox because a large proportion of non-lateralized (NL) individuals is commonly observed in animal populations. Hemispheric specialization often determines large left–right differences in perceiving and responding to stimuli. Using topminnows selected for a high or low degree of lateralization, we tested the hypothesis that individuals with greater functional asymmetry pay a higher performance cost in situations requiring matching information from the two eyes. When trained to use the middle door in a row of a nine, NL fish correctly chose the central door in most cases, while lateralized fish showed systematic leftward or rightward biases. When choosing between two shoals, each seen with a different eye, NL fish chose the high-quality shoal significantly more often than the lateralized fish, whose performance was affected by eye preference for analysing social stimuli. These findings suggest the existence of a trade-off between computational advantages of hemispheric specialization and the ecological cost of making suboptimal decisions whenever relevant information is located on both sides of the body. PMID:19793754

Isolation and characterization of the genes for two small RNAs of herpesvirus papio and their comparison with Epstein-Barr virus-encoded EBER RNAs.

PubMed

Howe, J G; Shu, M D

1988-08-01

Genes for the Epstein-Barr virus-encoded RNAs (EBERs), two low-molecular-weight RNAs encoded by the human gammaherpesvirus Epstein-Barr virus (EBV), hybridize to two small RNAs in a baboon cell line that contains a similar virus, herpesvirus papio (HVP). The genes for the HVP RNAs (HVP-1 and HVP-2) are located together in the small unique region at the left end of the viral genome and are transcribed by RNA polymerase III in a rightward direction, similar to the EBERs. There is significant similarity between EBER1 and HVP-1 RNA, except for an insert of 22 nucleotides which increases the length of HVP-1 RNA to 190 nucleotides. There is less similarity between the sequences of EBER2 and HVP-2 RNA, but both have a length of about 170 nucleotides. The predicted secondary structure of each HVP RNA is remarkably similar to that of the respective EBER, implying that the secondary structures are important for function. Upstream from the initiation sites of all four RNA genes are several highly conserved sequences which may function in the regulation of transcription. The HVP RNAs, together with the EBERs, are highly abundant in transformed cells and are efficiently bound by the cellular La protein.

Hemisphere- and gender-related differences in small-world brain networks: a resting-state functional MRI study.

PubMed

Tian, Lixia; Wang, Jinhui; Yan, Chaogan; He, Yong

2011-01-01

We employed resting-state functional MRI (R-fMRI) to investigate hemisphere- and gender-related differences in the topological organization of human brain functional networks. Brain networks were first constructed by measuring inter-regional temporal correlations of R-fMRI data within each hemisphere in 86 young, healthy, right-handed adults (38 males and 48 females) followed by a graph-theory analysis. The hemispheric networks exhibit small-world attributes (high clustering and short paths) that are compatible with previous results in the whole-brain functional networks. Furthermore, we found that compared with females, males have a higher normalized clustering coefficient in the right hemispheric network but a lower clustering coefficient in the left hemispheric network, suggesting a gender-hemisphere interaction. Moreover, we observed significant hemisphere-related differences in the regional nodal characteristics in various brain regions, such as the frontal and occipital regions (leftward asymmetry) and the temporal regions (rightward asymmetry), findings that are consistent with previous studies of brain structural and functional asymmetries. Together, our results suggest that the topological organization of human brain functional networks is associated with gender and hemispheres, and they provide insights into the understanding of functional substrates underlying individual differences in behaviors and cognition. Copyright © 2010 Elsevier Inc. All rights reserved.

Unusual developmental pattern of brain lateralization in young boys with autism spectrum disorder: Power analysis with child-sized magnetoencephalography.

PubMed

Hiraishi, Hirotoshi; Kikuchi, Mitsuru; Yoshimura, Yuko; Kitagawa, Sachiko; Hasegawa, Chiaki; Munesue, Toshio; Takesaki, Natsumi; Ono, Yasuki; Takahashi, Tsutomu; Suzuki, Michio; Higashida, Haruhiro; Asada, Minoru; Minabe, Yoshio

2015-03-01

Autism spectrum disorder (ASD) is often described as comprising an unusual brain growth pattern and aberrant brain lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, examples of physiological brain lateralization in young children with ASD have yet to be well examined. Thirty-eight boys with ASD (aged 3-7 years) and 38 typically developing (TD) boys (aged 3-8 years) concentrated on video programs and their brain activities were measured non-invasively. We employed a customized child-sized magnetoencephalography system in which the sensors were located as close to the brain as possible for optimal recording in young children. To produce a credible laterality index of the brain oscillations, we defined two clusters of sensors corresponding to the right and left hemispheres. We focused on the laterality index ([left - right]/[left+right]) of the relative power band in seven frequency bands. The TD group displayed significantly rightward lateralized brain oscillations in the theta-1 frequency bands compared to the ASD group. This is the first study to demonstrate unusual brain lateralization of brain oscillations measured by magnetoencephalography in young children with ASD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Effects of Filtering Visual Short Wavelengths During Nocturnal Shiftwork on Sleep and Performance

PubMed Central

Rahman, Shadab A.; Shapiro, Colin M.; Wang, Flora; Ainlay, Hailey; Kazmi, Syeda; Brown, Theodore J.

2013-01-01

Circadian phase resetting is sensitive to visual short wavelengths (450–480 nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480 nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age ± SD: 31.3 ± 4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2 h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p < 0.01) and sleep efficiency (p = 0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p = 0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40 min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p < 0.05) and middle (p < 0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p < 0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers. (Author correspondence: casper@lunenfeld.ca) PMID:23834705

Oxidative stress and insulin resistance in policemen working shifts.

PubMed

Demir, Irfan; Toker, Aysun; Zengin, Selcuk; Laloglu, Esra; Aksoy, Hulya

2016-04-01

Shift work is a work schedule involving irregular or unusual hours, compared to those of a normal daytime work schedule. In developed countries, night shift work is very common. In several cities of our country, 12/24 shift system is implemented in police organization. While night shift work composes half of the 20 shift in a month, in ergonomic shift system, an alternative shift schedule, shift work can be performed in three shifts in a day. In this study, we aimed to investigate the effects of 12/24 shift work system on insulin resistance and oxidative stress and systemic inflammation. Two hundred and four 12/24 shift workers (age 44.3 ± 5.6 years) and 193 ergonomic shift workers (age 42.6 ± 5.5 years) were included to study. Serum oxidized LDL (ox-LDL), neutrophil gelatinase lipocalin-2 (NGAL) as oxidative stress markers, glucose, insulin, ferritin, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate values were measured. Homeostasis model assessment for insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. Serum ox-LDL, HOMA-IR, hsCRP and NGAL levels in 12/24 shift system were found to be significantly higher compared with ergonomic shift workers (p < 0.0001, p = 0.02, p = 0.03, p = 0.02, respectively). When evaluated all subjects, weak but significant correlation was found between HOMA-IR with ox-LDL (r = 0.12, p = 0.01), hsCRP (r = 0.17, p = 0.001) and ferritin (r = 0.15, r = 0.003). Also in 12/24 shift work group, there were significant correlations between HOMA-IR with hsCRP (r = 0.17, p = 0.01) and ferritin (r = 0.25, p = 0.0001). It may be concluded that 12/24 shift system might give rise to insulin resistance and oxidative stress. Additionally, workers in this system may under risk of systemic inflammatory response. Working hours must be arranged in accordance with the physiological rhythm.

Night shift work exposure profile and obesity: Baseline results from a Chinese night shift worker cohort.

PubMed

Sun, Miaomiao; Feng, Wenting; Wang, Feng; Zhang, Liuzhuo; Wu, Zijun; Li, Zhimin; Zhang, Bo; He, Yonghua; Xie, Shaohua; Li, Mengjie; Fok, Joan P C; Tse, Gary; Wong, Martin C S; Tang, Jin-Ling; Wong, Samuel Y S; Vlaanderen, Jelle; Evans, Greg; Vermeulen, Roel; Tse, Lap Ah

2018-01-01

This study aimed to evaluate the associations between types of night shift work and different indices of obesity using the baseline information from a prospective cohort study of night shift workers in China. A total of 3,871 workers from five companies were recruited from the baseline survey. A structured self-administered questionnaire was employed to collect the participants' demographic information, lifetime working history, and lifestyle habits. Participants were grouped into rotating, permanent and irregular night shift work groups. Anthropometric parameters were assessed by healthcare professionals. Multiple logistic regression models were used to evaluate the associations between night shift work and different indices of obesity. Night shift workers had increased risk of overweight and obesity, and odds ratios (ORs) were 1.17 (95% CI, 0.97-1.41) and 1.27 (95% CI, 0.74-2.18), respectively. Abdominal obesity had a significant but marginal association with night shift work (OR = 1.20, 95% CI, 1.01-1.43). A positive gradient between the number of years of night shift work and overweight or abdominal obesity was observed. Permanent night shift work showed the highest odds of being overweight (OR = 3.94, 95% CI, 1.40-11.03) and having increased abdominal obesity (OR = 3.34, 95% CI, 1.19-9.37). Irregular night shift work was also significantly associated with overweight (OR = 1.56, 95% CI, 1.13-2.14), but its association with abdominal obesity was borderline (OR = 1.26, 95% CI, 0.94-1.69). By contrast, the association between rotating night shift work and these parameters was not significant. Permanent and irregular night shift work were more likely to be associated with overweight or abdominal obesity than rotating night shift work. These associations need to be verified in prospective cohort studies.

Effects of night shift working on some immunological, prostate specific antigen, cortisol level and malondialdehyde in male nurses at Hawler city

NASA Astrophysics Data System (ADS)

Muhammad, Dilshad Hussein; Qadir, Fikry Ali

2017-09-01

The present study was carried out to show the effects of nightshift working on some immunological, serum cortisol level, and malondialdehyde (MDA) on male nurses in Hawler city hospitals. After performing the exclusion and inclusion criteria, ninety-six male nurses were participated in this study. According to working shifts, the participants were divided into two groups. First group includes sixty seven night-shift male nurses working for 3-12 years with 8-10 nights/month. The second group consisted of twenty-nine day-shift male nurses working for 3-12 years. The age range of both groups was (≥20-40≤). The second group was used as a control group for statistical comparison. The results showed that night-shift working in male nurses was associated with significant increases in tumor necrosis factor-α (TNF-α) (77.15 ± 3.328 vs.101.1 ± 6.968, p=0.024), interleukin-2 (IL-2) (1147 ± 59.54vs1626 ± 34.71, p=0.001), and interferon-γ (IFN-γ) (272.3 ± 16.00 vs. 319.6 ± 12.48, p=0.029) when compared with day-shift group. Two-fold significant increase of high-sensitive C-reactive protein (hs-CRP) (3154 ± 403.3 vs. 6739 ± 334.0, p=0.001) was found in nightshift group as compared with day-shift group. Prostate specific antigen (PSA) estimation showed no significant increase in night-shift group in comparison with day-shift group (1.755 ± 0.202 vs. 1.987 ± 0.159, p=0.424). The results also showed that night-shift working was associated with significant elevations in serum cortisol levels when compared with dayshift nurses (7.844 ± 0.529 vs. 11.18 ± 0.406, p=0.001). Similar significant increasing was also observed for serum malondialdehyde (MDA) (1.124 ± 0.075 vs. 1.681 ± 0.079, p=0.001) in night-shift group when compared with day-shift group.

Prevalence of Sleep Disorders and Their Impacts on Occupational Performance: A Comparison between Shift Workers and Nonshift Workers

PubMed Central

Yazdi, Zohreh; Sadeghniiat-Haghighi, Khosro; Loukzadeh, Ziba; Elmizadeh, Khadijeh; Abbasi, Mahnaz

2014-01-01

The consequences of sleep deprivation and sleepiness have been noted as the most important health problem in our modern society among shift workers. The objective of this study was to investigate the prevalence of sleep disorders and their possible effects on work performance in two groups of Iranian shift workers and nonshift workers. This study was designed as a cross-sectional study. The data were collected by PSQI, Berlin questionnaire, Epworth Sleepiness Scale, Insomnia Severity Index, and RLS Questionnaire. Occupational impact of different sleep disorders was detected by Occupational Impact of Sleep Disorder questionnaire. These questionnaires were filled in by 210 shift workers and 204 nonshift workers. There was no significant difference in the age, BMI, marital status, and years of employment in the two groups. Shift workers scored significantly higher in the OISD. The prevalence of insomnia, poor sleep quality, and daytime sleepiness was significantly higher in shift workers. Correlations between OISD scores and insomnia, sleep quality, and daytime sleepiness were significant. We concluded that sleep disorders should receive more attention as a robust indicator of work limitation. PMID:24977041

Effect of pre-donation fluid intake on fluid shift from interstitial to intravascular compartment in blood donors.

PubMed

Deepika, Chenna; Murugesan, Mohandoss; Shastry, Shamee

2018-02-01

Fluid shifts from interstitial to intravascular space during blood donation helps in compensating the lost blood volume. We aimed to determine the volume of fluid shift following donation in donors with and without pre-donation fluid intake. We studied the fluid shift in 325 blood donors prospectively. Donors were divided in groups- with no fluid intake (GI) and either water (GII) or oral rehydrating fluids (GIII) before donation. Fluid shift following donation was calculated based on the difference between the pre and post donation blood volume. The influence of oral fluid intake, age, gender and body mass index (BMI) on volume of fluid shift was analyzed. The fluid shift was significant between donors without fluids (GI: 127 ± 81 ml) and donors with fluid intake (GII & III: 96 ± 45 ml) (p < 0.05). The difference was not significant between donors with water intake (GII: 106 ± 52 ml) and oral rehydrating fluid intake (GIII: 87 ± 41 ml). The shifted fluid volume increased with increasing BMI and decreased with increasing age in females. The fluid shift increased in females than in males. The age, gender, BMI and VVR did not significantly contribute to the volume of fluid shift following donation. As per our observation, the oral fluids before donation might not contribute to increase in fluid shift in blood donors after donation. Copyright © 2017 Elsevier Ltd. All rights reserved.

What roles do team climate, roster control, and work life conflict play in shiftworkers' fatigue longitudinally?

PubMed

Pisarski, Anne; Barbour, Jennifer P

2014-05-01

The study aimed to examine shiftworkers fatigue and the longitudinal relationships that impact on fatigue such as team climate, work life conflict, control of shifts and shift type in shift working nurses. We used a quantitative survey methodology and analysed data with a moderated hierarchical multiple regression. After matching across two time periods 18 months apart, the sample consisted of 166 nurses from one Australian hospital. Of these nurses, 61 worked two rotating day shifts (morning & afternoon/evening) and 105 were rotating shiftworkers who worked three shifts (morning afternoon/evening and nights). The findings suggest that control over shift scheduling can have significant effects on fatigue for both two-shift and three-shift workers. A significant negative relationship between positive team climate and fatigue was moderated by shift type. At both Time 1 and Time 2, work life conflict was the strongest predictor of concurrent fatigue, but over time it was not. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Late chronotype and high social jetlag are associated with burnout in evening-shift workers: Assessment using the Chinese-version MCTQshift.

PubMed

Cheng, Wan-Ju; Hang, Liang-Wen

2018-04-16

Chronotypes are associated with shift work tolerance and sleep in shift workers, and sleep mediates the impact of shift work on mental health. However, the role of chronotype in the association between shift work and mental health has not been clarified. In this study, we aimed to examine the association between chronotype and burnout in shift workers, using the validated Munich ChronoType Questionnaire for shift workers (MCTQ shift ). A total of 288 shift workers with irregular shift frequencies were recruited and completed the Chinese-version MCTQ shift and the Morningness-Eveningness Questionnaire (MEQ). Chronotypes were assessed by the calculation of corrected mid-sleep time (MSF SC ) from mid-sleep time on free days (MSF) based on their exact shift schedules. Another 26 evening-shift nurses were monitored with actigraphy for at least two consecutive evening shifts and the following two free days. Burnout was evaluated using the Copenhagen Burnout Inventory. We found that MSF E SC , MSF E and mid-sleep time on workdays (MSW E ) had normal distributions and correlated significantly with MEQ scores (r = - 0.47, -0.45 and -0.47, respectively; all p < 0.001). MSW was more closely correlated with actigraphy-derived mid-sleep time on the free day before workdays than that on workdays (r = 0.61 and 0.48, respectively, p < 0.05). Sleep duration was significantly longer on workdays among evening-shift workers who slept late on workdays than those who slept early (β = 0.59, p < 0.001). After demographic and work characteristics were adjusted for in linear regression models, late chronotype and high social jetlag were associated with burnout scores in evening-shift workers. In conclusion, the Chinese-version MCTQ shift is a valid tool for chronotype assessment. Interventions to improve sleep in shift workers should be tailored to chronotype due to variations in sleep behavior. Late chronotype may be an inherent feature of mental health problems, because the association with burnout was significant in both day workers in previous studies and shift workers.

Fatal accidents following changes in daylight savings time: the American experience.

PubMed

Varughese; Allen

2001-01-01

Objective: This study examines specific hypotheses that both sleep loss and behavioral changes occurring with the time shifts for Daylight Savings Time (DST) significantly effect the number of fatal traffic accidents in the United States of America.Background: It has been reported that there is a significant increase in the number of automobile accidents in the spring shift to DST due to the loss of 1 h of sleep. But the extra hour gained at night with the shift from DST in the fall has been variably reported to be associated with increases and decreases in the number of automobile accidents which may reflect either behavioral anticipation with an extended late night prior to the change or the benefit of extra sleep after the change.Methods: Data from 21 years of United States' fatal automobile accidents were gathered. The mean number of accidents on the days at the time of the shifts (Saturday, Sunday and Monday) was compared to the average of the corresponding mean number of accidents on the matching day of the weeks preceding and following the shift. This was repeated for each DST shift. The number of accidents for a particular shift was also correlated with the year of the accidents.Results: There was a significant increase in accidents for the Monday immediately following the spring shift to DST (t=1.92, P=0.034). There was also a significant increase in number of accidents on the Sunday of the fall shift from DST (P<0.002). No significant changes were observed for the other days. A significant negative correlation with the year was found between the number of accidents on the Saturdays and Sundays but not Mondays.Conclusions: The sleep deprivation on the Monday following shift to DST in the spring results in a small increase in fatal accidents. The behavioral adaptation anticipating the longer day on Sunday of the shift from DST in the fall leads to an increased number of accidents suggesting an increase in late night (early Sunday morning) driving when traffic related fatalities are high possibly related to alcohol consumption and driving while sleepy. Public health educators should probably consider issuing warnings both about the effects of sleep loss in the spring shift and possible behaviors such as staying out later, particularly when consuming alcohol in the fall shift. Sleep clinicians should be aware that health consequences from forced changes in the circadian patterns resulting from DST come not only from physiological adjustments but also from behavioral responses to forced circadian changes.

Effects of head tilt on visual field testing with a head-mounted perimeter imo

PubMed Central

Matsumoto, Chota; Nomoto, Hiroki; Numata, Takuya; Eura, Mariko; Yamashita, Marika; Hashimoto, Shigeki; Okuyama, Sachiko; Kimura, Shinji; Yamanaka, Kenzo; Chiba, Yasutaka; Aihara, Makoto; Shimomura, Yoshikazu

2017-01-01

Purpose A newly developed head-mounted perimeter termed “imo” enables visual field (VF) testing without a fixed head position. Because the positional relationship between the subject’s head and the imo is fixed, the effects of head position changes on the test results are small compared with those obtained using a stationary perimeter. However, only ocular counter-roll (OCR) induced by head tilt might affect VF testing. To quantitatively reveal the effects of head tilt and OCR on the VF test results, we investigated the associations among the head-tilt angle, OCR amplitude and VF testing results. Subjects and methods For 20 healthy subjects, we binocularly recorded static OCR (s-OCR) while tilting the subject’s head at an arbitrary angle ranging from 0° to 60° rightward or leftward in 10° increments. By monitoring iris patterns, we evaluated the s-OCR amplitude. We also performed blind spot detection while tilting the subject’s head by an arbitrary angle ranging from 0° to 50° rightward or leftward in 10° increments to calculate the angle by which the blind spot rotates because of head tilt. Results The association between s-OCR amplitude and head-tilt angle showed a sinusoidal relationship. In blind spot detection, the blind spot rotated to the opposite direction of the head tilt, and the association between the rotation angle of the blind spot and the head-tilt angle also showed a sinusoidal relationship. The rotation angle of the blind spot was strongly correlated with the s-OCR amplitude (R2≥0.94, p<0.0001). A head tilt greater than 20° with imo causes interference between adjacent test areas. Conclusions Both the s-OCR amplitude and the rotation angle of the blind spot were correlated with the head-tilt angle by sinusoidal regression. The rotated VF was correlated with the s-OCR amplitude. During perimetry using imo, the change in the subject’s head tilt should be limited to 20°. PMID:28945777

Change from slowly rotating 8-hour shifts to rapidly rotating 8-hour and 12-hour shifts using participative shift roster design.

PubMed

Smith, P A; Wright, B M; Mackey, R W; Milsop, H W; Yates, S C

1998-01-01

The study examined the impact of change, from slowly rotating continuous 8-hour shifts to more rapidly rotating continuous 8-hour and 12-hour shifts, on the health and quality of life of shift workers. Self-report survey data were collected from 72 shift workers at 3 sewage treatment plants before and several months after roster change. After the change 1 plant first worked a rapidly rotating, 8-hour shift roster and then worked a 12-hour shift roster, and the other 2 plants worked continuous 12-hour shift rosters. After the change the shift workers at each plant reported increased satisfaction with roster design, a decrease in physical and psychological circadian malaise associated with shift work, improved day sleep quality, less tiredness, and improvements in the quality of home, social and work life. A between-plant comparison of the rapidly rotating 8-hour and 12-hour shift rosters showed greater improvements had been obtained with the 12-hour shift roster, and no significant differences in tiredness or sleep quality between the redesigned 8- and 12-hour shift rosters. However, a within-plant matched-pairs comparison at the 1st plant of the rapidly rotating 8-hour shift roster and the 12-hour shift roster showed no significant differences. The results show that the prior level of support for change may best explain the impact of roster redesign on individual well-being. They lend further support to shift worker participation in roster design.

Association between shift work and obesity among female nurses: Korean Nurses’ Survey

PubMed Central

2013-01-01

Background Shift work has been hypothesized as a risk factor for obesity. In this study, we investigated the association between current shift work and body mass index (BMI) among female nurses in Korea. The relationship between duration of shift work and BMI of the participants was also evaluated. Methods This cross-sectional survey evaluated participants in the Korean Nurses’ Survey, conducted from October to December 2011, using web-based self-administered questionnaires. A total of 9,989 nurses were included among 10,000 who registered on the survey web site (5,287 shift workers and 4,702 non-shift workers). Current shift workers were divided into tertiles of shift work duration (0.08–3.00 years, n = 1,732; 3.08–6.75 years, n = 1,731; and 6.83–38.00 years, n = 1,686). The BMI thresholds of overweight and obesity were ≥23 kg/m2 and ≥25 kg/m2, respectively. Data were analyzed using SPSS software. Results Mean participant age was 33.2 ± 8.6 years and the mean BMI was 20.9 ± 2.5 kg/m2. There were statistically significant differences in current smoking status, regular drinking habit, dietary habits, regular exercise, sleep problems and self-perceived health status according to duration of shift work. The overall prevalence of overweight/obesity (18.6%) and obesity (7.4%) increased significantly as shift work duration increased from the lowest to highest tertile (P for trend <0.001). Multivariate logistic regression analysis revealed no association between current shift work and BMI. However, after adjusting for potential confounders, the participants with the longest duration of shift work were 1.63 (95% CI, 1.22–2.17) times more likely to be overweight or obese than those with the shortest duration. There was a significant positive association between obesity and shift work duration in the unadjusted analysis; however, it was attenuated and no longer significant in the multivariate model. Conclusions The duration of shift work was positively associated with prevalence of overweight/obesity in nurses in Korea. Although these findings need to be confirmed in prospective studies, they suggest that special attention should be paid to female nurses with a long duration of shift work. PMID:24354395

The impact of shift work on the psychological and physical health of nurses in a general hospital: a comparison between rotating night shifts and day shifts.

PubMed

Ferri, Paola; Guadi, Matteo; Marcheselli, Luigi; Balduzzi, Sara; Magnani, Daniela; Di Lorenzo, Rosaria

2016-01-01

Shift work is considered necessary to ensure continuity of care in hospitals and residential facilities. In particular, the night shift is one of the most frequent reasons for the disruption of circadian rhythms, causing significant alterations of sleep and biological functions that can affect physical and psychological well-being and negatively impact work performance. The aim of this study was to highlight if shift work with nights, as compared with day work only, is associated with risk factors predisposing nurses to poorer health conditions and lower job satisfaction. This cross-sectional study was conducted from June 1, 2015 to July 31, 2015 in 17 wards of a general hospital and a residential facility of a northern Italian city. This study involved 213 nurses working in rotating night shifts and 65 in day shifts. The instrument used for data collection was the "Standard Shift Work Index," validated in Italian. Data were statistically analyzed. The response rate was 86%. The nurses engaged in rotating night shifts were statistically significantly younger, more frequently single, and had Bachelors and Masters degrees in nursing. They reported the lowest mean score in the items of job satisfaction, quality and quantity of sleep, with more frequent chronic fatigue, psychological, and cardiovascular symptoms in comparison with the day shift workers, in a statistically significant way. Our results suggest that nurses with rotating night schedule need special attention due to the higher risk for both job dissatisfaction and undesirable health effects.

Influence of night-shift and napping at work on urinary melatonin, 17-β-estradiol and clock gene expression in pre-menopausal nurses.

PubMed

Bracci, M; Copertaro, A; Manzella, N; Staffolani, S; Strafella, E; Nocchi, L; Barbaresi, M; Copertaro, B; Rapisarda, V; Valentino, M; Santarelli, L

2013-01-01

Night-workers experience disruption of the sleep-wake cycle and light at night which may increase breast cancer risk by suppressing the nocturnal melatonin surge, resulting in higher levels of circulating estrogens. Night-work may also deregulate peripheral clock genes which have been found to be altered in breast cancer. This study investigated urinary 6-sulfatoxymelatonin (aMT6s), serum 17-beta-estradiol levels in premenopausal shift nurses at the end of the night-shift compared to a control group of daytime nurses. Peripheral clock gene expression in lymphocytes were also investigated. All participants were sampled in the follicular phase of the menstrual cycle. The effect of nurses’ ability to take a short nap during the night-shift was also explored. The shift-work group had significantly lower aMT6s levels than daytime nurses independently of a nap. Night-shift napping significantly influences 17-beta-estradiol levels resulting in higher outcomes in nurses who do not take a nap compared to napping group and daytime workers. Peripheral clock genes expression investigated was not significantly different among the groups. Our findings suggest that shift nurses experience changes in aMT6s levels after a night-shift. Napping habits influence 17-beta-estradiol levels at the end of a night-shift. These findings might be related to the increased cancer risk reported in night-shift workers and suggest that a short nap during night-shifts may exert a positive effect.

Night-shift work is associated with poorer glycaemic control in patients with type 2 diabetes.

PubMed

Manodpitipong, Areesa; Saetung, Sunee; Nimitphong, Hataikarn; Siwasaranond, Nantaporn; Wongphan, Thanawat; Sornsiriwong, Chotima; Luckanajantachote, Pranee; Mangjit, Prasitchai; Keesukphan, Prasit; Crowley, Stephanie J; Hood, Megan M; Reutrakul, Sirimon

2017-12-01

The circadian system plays a role in regulating metabolism. Night-shift work, a form of circadian misalignment, is associated with increased type 2 diabetes risk. This study aimed to determine if night-shift workers with type 2 diabetes experience poorer glycaemic control than non-shift workers. Patients with type 2 diabetes (104 unemployed, 85 day workers and 60 night-shift workers) participated. Sleep duration, sleep quality, morningness-eveningness preference, depressive symptoms and dietary intake were assessed using standardized questionnaires. Haemoglobin A1c levels were measured. Night-shift workers had significantly higher haemoglobin A1c levels compared with others, while there were no differences between day workers and unemployed participants (median 7.86% versus 7.24% versus 7.09%, respectively). Additionally, night-shift workers were younger, had a higher body mass index, and consumed more daily calories than others. Among night-shift workers, there were no significant differences in haemoglobin A1c levels between those performing rotating versus non-rotating shifts (P = 0.856), or those with clockwise versus counterclockwise shift rotation (P = 0.833). After adjusting for age, body mass index, insulin use, sleep duration, morningness-eveningness preference and percentage of daily intake from carbohydrates, night-shift work, compared with day work, was associated with significantly higher haemoglobin A1c (B = 0.059, P = 0.044), while there were no differences between unemployed participants and day workers (B = 0.016, P = 0.572). In summary, night-shift work is associated with poorer glycaemic control in patients with type 2 diabetes. © The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

Diet quality and sleep quality among day and night shift nurses.

PubMed

Beebe, Deborah; Chang, Jen Jen; Kress, Kathleen; Mattfeldt-Beman, Mildred

2017-10-01

To determine whether night shift workers have a poorer diet quality and sleep quality when compared with day shift nurses. There is a dearth of research investigating the association between diet quality and sleep quality of day and night shift nurses. Data on nurses (n = 103) working either a day or night shift from two Midwestern hospitals were obtained from August 2015 to February 2016. The instruments used were the Diet History Questionnaire and the Pittsburg Sleep Quality Index. Independent samples t-tests were used to examine differences in diet and sleep quality by work shift schedule. There were no statistically significant differences between nurses working day or night shift and sleep quality (P = 0.0684), as well as diet quality (P = 0.6499). There was a significant difference between both body mass index (P = 0.0014) and exercise (P = 0.0020) with regard to diet quality. Body mass index and sleep quality were also significantly associated (P = 0.0032). Our study found no differences between day and night shift with regard to sleep and diet quality among nurses. Deliberate health initiatives and wellness programmes specifically targeting nurses are needed to increase knowledge about maintaining a healthy lifestyle while working as a nurse, whether it is day or night shift. © 2017 John Wiley & Sons Ltd.

Perception of combined translation and rotation in the horizontal plane in humans

PubMed Central

2016-01-01

Thresholds and biases of human motion perception were determined for yaw rotation and sway (left-right) and surge (fore-aft) translation, independently and in combination. Stimuli were 1 Hz sinusoid in acceleration with a peak velocity of 14°/s or cm/s. Test stimuli were adjusted based on prior responses, whereas the distracting stimulus was constant. Seventeen human subjects between the ages of 20 and 83 completed the experiments and were divided into 2 groups: younger and older than 50. Both sway and surge translation thresholds significantly increased when combined with yaw rotation. Rotation thresholds were not significantly increased by the presence of translation. The presence of a yaw distractor significantly biased perception of sway translation, such that during 14°/s leftward rotation, the point of subjective equality (PSE) occurred with sway of 3.2 ± 0.7 (mean ± SE) cm/s to the right. Likewise, during 14°/s rightward motion, the PSE was with sway of 2.9 ± 0.7 cm/s to the left. A sway distractor did not bias rotation perception. When subjects were asked to report the direction of translation while varying the axis of yaw rotation, the PSE at which translation was equally likely to be perceived in either direction was 29 ± 11 cm anterior to the midline. These results demonstrated that rotation biased translation perception, such that it is minimized when rotating about an axis anterior to the head. Since the combination of translation and rotation during ambulation is consistent with an axis anterior to the head, this may reflect a mechanism by which movements outside the pattern that occurs during ambulation are perceived. PMID:27334952

Prism adaptation and neck muscle vibration in healthy individuals: are two methods better than one?

PubMed

Guinet, M; Michel, C

2013-12-19

Studies involving therapeutic combinations reveal an important benefit in the rehabilitation of neglect patients when compared to single therapies. In light of these observations our present work examines, in healthy individuals, sensorimotor and cognitive after-effects of prism adaptation and neck muscle vibration applied individually or simultaneously. We explored sensorimotor after-effects on visuo-manual open-loop pointing, visual and proprioceptive straight-ahead estimations. We assessed cognitive after-effects on the line bisection task. Fifty-four healthy participants were divided into six groups designated according to the exposure procedure used with each: 'Prism' (P) group; 'Vibration with a sensation of body rotation' (Vb) group; 'Vibration with a move illusion of the LED' (Vl) group; 'Association with a sensation of body rotation' (Ab) group; 'Association with a move illusion of the LED' (Al) group; and 'Control' (C) group. The main findings showed that prism adaptation applied alone or combined with vibration showed significant adaptation in visuo-manual open-loop pointing, visual straight-ahead and proprioceptive straight-ahead. Vibration alone produced significant after-effects on proprioceptive straight-ahead estimation in the Vl group. Furthermore all groups (except C group) showed a rightward neglect-like bias in line bisection following the training procedure. This is the first demonstration of cognitive after-effects following neck muscle vibration in healthy individuals. The simultaneous application of both methods did not produce significant greater after-effects than prism adaptation alone in both sensorimotor and cognitive tasks. These results are discussed in terms of transfer of sensorimotor plasticity to spatial cognition in healthy individuals. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Flexion-rotation manoeuvre increases dimension of the acoustic target window for paramedian thoracic epidural access.

PubMed

Ramsay, N; Walker, J; Tang, R; Vaghadia, H; Sawka, A

2014-03-01

The posterior longitudinal ligament (PLL) has been found to be a reliable measure of the acoustic target window for lumbar spinal anaesthesia and a predictive tool for difficult spinals. Currently, there is limited information on the PLL in the thoracic spine and its potential use for optimizing the acoustic target window during thoracic epidural placement. This study examined the effects of changes in body position on the length of the PLL as a measure of the acoustic target window for paramedian thoracic epidural access. We performed thoracic ultrasonography on 30 adult volunteers to measure the length of the PLL at the T9/10 interspace, in five different positions: P1, neutral; P2, thoracic and lumbar flexion; P3, as in position 2 with dorsal table tilt to 10°; P4, as in position 2 with 45° rightward shoulder rotation; and P5, as in position 2 with 45° leftward shoulder rotation. The mean (sd) PLL length increased significantly from 9.9 (3.9) mm in P1 to 11.7 (3.4) mm in P2, 12.9 (3.1) mm in P3, and 13.8 (4.0) mm in P4 (P<0.01, <0.01, and <0.01, respectively). The mean PLL length in P3 and P4 was also significantly longer compared with P2 (P<0.01 and 0.01, respectively). In volunteers, flexion with 10° dorsal table tilt and flexion with right rotation significantly increased the length of the ipsilateral PLL, compared with the standard flexed sitting position, as visualized by paramedian ultrasonography at the level of T9/10.

Graph theory analysis of cortical thickness networks in adolescents with d-transposition of the great arteries.

PubMed

Watson, Christopher G; Stopp, Christian; Newburger, Jane W; Rivkin, Michael J

2018-02-01

Adolescents with d-transposition of the great arteries (d-TGA) who had the arterial switch operation in infancy have been found to have structural brain differences compared to healthy controls. We used cortical thickness measurements obtained from structural brain MRI to determine group differences in global brain organization using a graph theoretical approach. Ninety-two d-TGA subjects and 49 controls were scanned using one of two identical 1.5-Tesla MRI systems. Mean cortical thickness was obtained from 34 regions per hemisphere using Freesurfer. A linear model was used for each brain region to adjust for subject age, sex, and scanning location. Structural connectivity for each group was inferred based on the presence of high inter-regional correlations of the linear model residuals, and binary connectivity matrices were created by thresholding over a range of correlation values for each group. Graph theory analysis was performed using packages in R. Permutation tests were performed to determine significance of between-group differences in global network measures. Within-group connectivity patterns were qualitatively different between groups. At lower network densities, controls had significantly more long-range connections. The location and number of hub regions differed between groups: controls had a greater number of hubs at most network densities. The control network had a significant rightward asymmetry compared to the d-TGA group at all network densities. Using graph theory analysis of cortical thickness correlations, we found differences in brain structural network organization among d-TGA adolescents compared to controls. These may be related to the white matter and gray matter differences previously found in this cohort, and in turn may be related to the cognitive deficits this cohort presents.

Shift Work and the Relationship with Metabolic Syndrome in Chinese Aged Workers

PubMed Central

Guo, Yanjun; Rong, Yi; Huang, Xiji; Lai, Hanpeng; Luo, Xin; Zhang, Zhihong; Liu, Yuewei; He, Meian; Wu, Tangchun; Chen, Weihong

2015-01-01

Background Shift work is indicated to be associated with adverse metabolic disorders. However, potential effects of shift work on metabolic syndrome (MetS) and its components have not been well established. Methods In total, 26,382 workers from Dongfeng-Tongji Cohort were included in this study. Information on shift work history was gathered through questionnaires and metabolic traits were measured. Logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) for long-term shift work related with MetS and each component, respectively. Further stratification analysis was performed to detect the differences on MetS between female and male shift workers. Results Long-term shift work was associated with MetS without adjusting for any confounders. Compared with the group of non-shift work, the multivariate-adjusted ORs (95%CI) of MetS associated with 1–10, 11−20, and ≥20y of shift work were 1.05 (0.95−1.16), 1.14 (1.03−1.26), 1.16 (1.01−1.31), respectively. In female workers, we found a dose-response relationship that every 10 years increase in shift work was associated with a 10% (95% CI: 1%−20%) elevated OR of MetS, while no significant dose-response trend was found among male workers. Furthermore, shift work duration was significantly associated with ORs of high blood pressure (1.07, 1.01−1.13), long waist circumference (1.10, 1.01−1.20) and high glucose levels (1.09, 1.04−1.15). No significant association was observed between shift work and low HDL cholesterol) and raised triglyceride levels. Conclusions Long-term shift work was associated with metabolic syndrome and the association might differ by gender in retired workers. Applicable intervention strategies are needed for prevention of metabolic disorders for shift workers. PMID:25761114

Night shift work exposure profile and obesity: Baseline results from a Chinese night shift worker cohort

PubMed Central

Feng, Wenting; Wang, Feng; Zhang, Liuzhuo; Wu, Zijun; Li, Zhimin; Zhang, Bo; He, Yonghua; Xie, Shaohua; Li, Mengjie; Fok, Joan P. C.; Tse, Gary; Wong, Martin C. S.; Tang, Jin-ling; Wong, Samuel Y. S.; Vlaanderen, Jelle; Evans, Greg; Vermeulen, Roel; Tse, Lap Ah

2018-01-01

Aims This study aimed to evaluate the associations between types of night shift work and different indices of obesity using the baseline information from a prospective cohort study of night shift workers in China. Methods A total of 3,871 workers from five companies were recruited from the baseline survey. A structured self-administered questionnaire was employed to collect the participants’ demographic information, lifetime working history, and lifestyle habits. Participants were grouped into rotating, permanent and irregular night shift work groups. Anthropometric parameters were assessed by healthcare professionals. Multiple logistic regression models were used to evaluate the associations between night shift work and different indices of obesity. Results Night shift workers had increased risk of overweight and obesity, and odds ratios (ORs) were 1.17 (95% CI, 0.97–1.41) and 1.27 (95% CI, 0.74–2.18), respectively. Abdominal obesity had a significant but marginal association with night shift work (OR = 1.20, 95% CI, 1.01–1.43). A positive gradient between the number of years of night shift work and overweight or abdominal obesity was observed. Permanent night shift work showed the highest odds of being overweight (OR = 3.94, 95% CI, 1.40–11.03) and having increased abdominal obesity (OR = 3.34, 95% CI, 1.19–9.37). Irregular night shift work was also significantly associated with overweight (OR = 1.56, 95% CI, 1.13–2.14), but its association with abdominal obesity was borderline (OR = 1.26, 95% CI, 0.94–1.69). By contrast, the association between rotating night shift work and these parameters was not significant. Conclusion Permanent and irregular night shift work were more likely to be associated with overweight or abdominal obesity than rotating night shift work. These associations need to be verified in prospective cohort studies. PMID:29763461

Changes in precipitation regime in the Baltic countries in 1966-2015

NASA Astrophysics Data System (ADS)

Jaagus, Jaak; Briede, Agrita; Rimkus, Egidijus; Sepp, Mait

2018-01-01

The aim of the study was to analyse trends and regime shifts in time series of monthly, seasonal and annual precipitation in the eastern Baltic countries (Lithuania, Latvia, Estonia) during 1966-2015. Data from 54 stations with nearly homogeneous series were used. The Mann-Kendall test was used for trend analysis and the Rodionov test for the analysis of regime shifts. Rather few statistically significant trends ( p < 0.05) and regime shifts were determined. The highest increase (by approximately 10 mm per decade) was observed in winter precipitation when a significant trend was found at the large majority of stations. For monthly precipitation, increasing trends were detected at many stations in January, February and June. Weak negative trends revealed at few stations in April and September. Annual precipitation has generally increased, but the trend is mostly insignificant. The analysis of regime shifts revealed some significant abrupt changes, the most important of which were upward shifts in winter, in January and February precipitation at many stations since 1990 or in some other years (1989, 1995). A return shift in the time series of February precipitation occurred since 2003. The most significant increase in precipitation was determined in Latvia and the weakest increase in Lithuania.

Conditional heteroscedasticity as a leading indicator of ecological regime shifts.

PubMed

Seekell, David A; Carpenter, Stephen R; Pace, Michael L

2011-10-01

Regime shifts are massive, often irreversible, rearrangements of nonlinear ecological processes that occur when systems pass critical transition points. Ecological regime shifts sometimes have severe consequences for human well-being, including eutrophication in lakes, desertification, and species extinctions. Theoretical and laboratory evidence suggests that statistical anomalies may be detectable leading indicators of regime shifts in ecological time series, making it possible to foresee and potentially avert incipient regime shifts. Conditional heteroscedasticity is persistent variance characteristic of time series with clustered volatility. Here, we analyze conditional heteroscedasticity as a potential leading indicator of regime shifts in ecological time series. We evaluate conditional heteroscedasticity by using ecological models with and without four types of critical transition. On approaching transition points, all time series contain significant conditional heteroscedasticity. This signal is detected hundreds of time steps in advance of the regime shift. Time series without regime shifts do not have significant conditional heteroscedasticity. Because probability values are easily associated with tests for conditional heteroscedasticity, detection of false positives in time series without regime shifts is minimized. This property reduces the need for a reference system to compare with the perturbed system.

Co-occurring anxiety influences patterns of brain activity in depression.

PubMed

Engels, Anna S; Heller, Wendy; Spielberg, Jeffrey M; Warren, Stacie L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2010-03-01

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in the dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in the right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in the anterior cingulate cortex (dorsal ACC and rostral ACC) and the bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala).

Co-occurring Anxiety Influences Patterns of Brain Activity in Depression

PubMed Central

Engels, Anna S.; Heller, Wendy; Spielberg, Jeffrey M.; Warren, Stacie L.; Sutton, Bradley P.; Banich, Marie T.; Miller, Gregory A.

2011-01-01

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion-word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in anterior cingulate cortex (dACC and rACC) and bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala). PMID:20233962

[Vertebral artery dissection due to the C6 transverse process and laryngeal cartilage associated with vertebral artery anomaly].

PubMed

Kusunoki Nakamoto, Fumiko; Hashimoto Maeda, Meiko; Mori, Kentaro; Hara, Takayuki; Uesaka, Yoshikazu

2014-01-01

A 52-year-old woman complained of the sudden onset of a left temporal headache, left neck stiffness and dizziness. Brain magnetic resonance imaging showed a high-intensity lesion in the right medial medulla. Dynamic cerebral angiography revealed vertebral artery dissection and compression at the C6 level due to a transverse process at the C6 level associated with rightward head rotation. Removal of bone and decompression of the vertebral artery were performed from the C5 to C6 levels. Intraoperasively, obstruction of blood flow due to a laryngeal cartilage that rotated with the passive rotation of the patient's head to the right was found. To the best of our knowledge this is the first reported case of vertebral artery occlusion due to a laryngeal cartilage associated with head rotation.

Lateral organization and aesthetic preference: the importance of peripheral visual asymmetries.

PubMed

Beaumont, J G

1985-01-01

The observation that right-handers prefer pictures with the important content to the right was examined. In the first experiment, subjects manipulated the two elements of the composition. They showed a bias to place the principal object to the right and, with a central principal object, the secondary object was placed to the left. In a further experiment, eye movements were recorded while subjects scanned the pictures used in the first experiment and a rightward lateral bias in gaze direction was observed. It is argued that lateral asymmetry in preferred picture arrangements is not the result of a counterbalancing of content against perceptual bias, but a consequence of gaze being directed to informative content on the right, leaving more of the secondary content within the left visual field and associated with attentional bias or processes of the right hemisphere.

Circadian Rhythm of Wrist Temperature among Shift Workers in South Korea: A Prospective Observational Study

PubMed Central

Kim, Hyunjoo; Kang, Suk-Hoon; Choo, Sang-Hyo; Lee, In-Seok; Choi, Kyung-Hwa

2017-01-01

Background: Human body temperature varies with circadian rhythm. To determine the effect of shift work on the circadian rhythm of the distal-skin temperature, wrist temperatures were measured. Methods: Wrist-skin temperatures were measured by an iButton® Temperature Logger. It was measured every 3 min for two and eight consecutive working days in the day and shift workers, respectively. Mesor, amplitude, and acrophase were measured by Cosinor analysis. Results: The shift-worker amplitude dropped significantly as the night shift progressed (0.92 to 0.85 °C), dropped further during rest (0.69 °C), and rose during the morning-shift days (0.82 °C). Day workers still had higher amplitudes (0.93 °C) than the morning-shift workers. The acrophase was delayed during the four night-shift days, then advanced during rest days and the morning-shift days. Nevertheless, the morning-shift worker acrophase was still significantly delayed compared to the day workers (08:03 a.m. vs. 04:11 a.m.). Conclusions: The further reduction of wrist-temperature amplitude during rest after the night shift may be due to the signal circadian rhythm disruption. Reduced amplitudes have been reported to be associated with intolerance to shift work. The findings of our study may help to design the most desirable schedule for shift workers. PMID:28946653

Circadian Rhythm of Wrist Temperature among Shift Workers in South Korea: A Prospective Observational Study.

PubMed

Jang, Tae-Won; Kim, Hyunjoo; Kang, Suk-Hoon; Choo, Sang-Hyo; Lee, In-Seok; Choi, Kyung-Hwa

2017-09-24

Background : Human body temperature varies with circadian rhythm. To determine the effect of shift work on the circadian rhythm of the distal-skin temperature, wrist temperatures were measured. Methods : Wrist-skin temperatures were measured by an iButton ® Temperature Logger. It was measured every 3 min for two and eight consecutive working days in the day and shift workers, respectively. Mesor, amplitude, and acrophase were measured by Cosinor analysis. Results : The shift-worker amplitude dropped significantly as the night shift progressed (0.92 to 0.85 °C), dropped further during rest (0.69 °C), and rose during the morning-shift days (0.82 °C). Day workers still had higher amplitudes (0.93 °C) than the morning-shift workers. The acrophase was delayed during the four night-shift days, then advanced during rest days and the morning-shift days. Nevertheless, the morning-shift worker acrophase was still significantly delayed compared to the day workers (08:03 a.m. vs. 04:11 a.m.). Conclusions : The further reduction of wrist-temperature amplitude during rest after the night shift may be due to the signal circadian rhythm disruption. Reduced amplitudes have been reported to be associated with intolerance to shift work. The findings of our study may help to design the most desirable schedule for shift workers.

Catecholamine transport in isolated lung parenchyma of pig

PubMed Central

Goldie, Roy G.; Paterson, James W.

1982-01-01

1 Lung parenchyma strips of the pig incubated at 37°C with [3H]-(-)-noradrenaline ([3H]-NA) or [3H]-(±)-isoprenaline ([3H]-Iso), accumulated radioactivity via saturable, high affinity uptake processes. Apparent saturation constants (Km) for [3H]-NA and [3H]-Iso were 1.34 × 10-6 M and 1.63 × 10-6 M respectively, while apparent transport maxima (Vmax) were 4.86 and 1.63 × 10-9 mol min-1 g-1 respectively. 2 Cellular accumulation of radioactivity from radiolabelled catecholamines was greatly reduced by lowering the temperature to 7°C, pretreatment with ouabain (100 μM), phentolamine (15 μM) or phenoxybenzamine (80 μM). However, accumulation of radioactivity derived from (3H]-NA was inhibited selectively by cocaine (10 μM) and desipramine (1 μM), while normetanephrine (80 μM) and 3-O-methylisoprenaline (50 μM) caused much greater reductions in cellular radioactivity from [3H]-Iso than from (3H]-NA. Taken together with information from kinetic studies, the results indicate that these amines are transported by separate uptake processes. 3 Cocaine (50 μM) which selectively reduced [3H]-NA transport, had no significant effect on the sensitivity (EC50) of isolated parenchyma lung strips of the pig to the contractile effects of cumulative concentrations of NA. The catechol-O-methyl transferase (COMT) inhibitor, U-0521 (60 μM), also failed to alter the potency of NA, while normetanephrine (80 μM) caused a 2 fold decrease in potency. 4 Phentolamine (15 μM), which reduced the cellular accumulation of radioactivity derived from [3H]-Iso by 64%, caused a small potentiation of Iso-induced relaxations of porcine lung strips. Normetanephrine (80 μM) and 3-O-methylisoprenaline (50 μM), which also depressed the accumulation of cellular radioactivity from [3H]-Iso by > 50%, caused rightward shifts in Iso concentration-effect curves as a result of β-adrenoceptor blockade. In sharp contrast, cortisol (80 μM) and U-0521 (60 μM), which caused smaller reductions in the cellular accumulation of radioactivity derived from [3H]-Iso, both caused an approximately 9 fold potentiation of responses to Iso in isolated lung strips. 5 The results indicate that the major sites of uptake and metabolism of NA in porcine parenchyma strip are remote from α-adrenoceptors mediating NA-induced contraction. Similarly, some major sites of uptake of Iso are remote from β-adrenoceptors mediating Iso-induced relaxation. However, β-adrenoceptors are apparently in close proximity to a compartment containing COMT activity. PMID:7104521

β2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post-synaptic Potentials as a Potential Substrate

PubMed Central

Marek, Gerard J.; Ramos, Brian P.

2018-01-01

5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM). Epinephrine (0.3–10 μM) suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM) resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work appears to extend this suppressant action to a Gs-coupled GPCR. Furthermore, the modulation of 5-HT2A receptor activation-induced glutamate release onto mPFC layer V pyramidal neurons apical dendrites by a range GPCRs in rat brain slices appears to results in behaviorally salient effects of relevance when screening for novel CNS therapeutic drugs. PMID:29472863

Effect of beta-alanine supplementation on the onset of blood lactate accumulation (OBLA) during treadmill running: Pre/post 2 treatment experimental design.

PubMed

Jordan, Thomas; Lukaszuk, Judith; Misic, Mark; Umoren, Josephine

2010-05-19

beta-Alanine (betaA) has been shown to improve performance during cycling. This study was the first to examine the effects of betaA supplementation on the onset of blood lactate accumulation (OBLA) during incremental treadmill running. Seventeen recreationally-active men (mean +/- SE 24.9 +/- 4.7 yrs, 180.6 +/- 8.9 cm, 79.25 +/- 9.0 kg) participated in this randomized, double-blind, placebo-controlled pre/post test 2-treatment experimental design. Subjects participated in two incremental treadmill tests before and after 28 days of supplementation with either betaA (6.0 g.d-1)(betaA, n = 8) or an equivalent dose of Maltodextrin as the Placebo (PL, n = 9). Heart rate, percent heart rate maximum (%HRmax), %VO2max@OBLA (4.0 mmol.L-1 blood lactate concentration) and VO2max (L.min-1) were determined for each treadmill test. Friedman test was used to determine within group differences; and Mann-Whitney was used to determine between group differences for pre and post values (p < 0.05). The betaA group experienced a significant rightward shift in HR@OBLA beats.min-1 (p < 0.01) pre/post (161.6 +/- 19.2 to 173.6 +/- 9.9) but remained unchanged in the PL group (166.8 +/- 15.8 to 169.6 +/- 16.1). The %HRmax@OBLA increased (p < 0.05) pre/post in the betaA group (83.0% +/- 9.7 to 88.6% +/- 3.7) versus no change in the PL group (86.3 +/- % 4.8 to 87.9% +/- 7.2). The %VO2max@OBLA increased (p < 0.05) in the betaA group pre/post (69.1 +/- 11.0 to 75.6 +/- 10.7) but remained unchanged in the PL group (73.3 +/- 7.3 to 74.3 +/- 7.3). VO2max (L.min-1) decreased (p < 0.01) in the betaA group pre/post (4.57 +/- 0.8 to 4.31 +/- 0.8) versus no change in the PL group (4.04 +/- 0.7 to 4.18 +/- 0.8). Body mass kg increased (p < 0.05) in the betaA group pre/post (77.9 +/- 9.0 to 78.3 +/- 9.3) while the PL group was unchanged (80.6 +/- 9.1 to 80.4 +/- 9.0). betaA supplementation for 28 days enhanced sub-maximal endurance performance by delaying OBLA. However, betaA supplemented individuals had a reduced aerobic capacity as evidenced by the decrease in VO2max values post supplementation.

Association of eating behaviours with diurnal preference and rotating shift work in Japanese female nurses: a cross-sectional study

PubMed Central

Yoshizaki, Takahiro; Kawano, Yukari; Noguchi, Osamu; Onishi, Junko; Teramoto, Reiko; Sunami, Ayaka; Yokoyama, Yuri; Tada, Yuki; Hida, Azumi; Togo, Fumiharu

2016-01-01

Objectives Our study examines differences in eating behaviour between day workers and rotating shift workers, and considers whether diurnal preference could explain the differences. Methods Japanese female nurses were studied (39 day workers and 123 rotating shift workers, aged 21–63 years) using self-administered questionnaires. The questionnaires assessed eating behaviours, diurnal preference and demographic characteristics. The questionnaire in the Guidelines for the management of obesity disease issued by the Japan Society for the Study of Obesity was used to obtain scores for the levels of obesity-related eating behaviours, including cognition of constitution, motivation for eating, eating as a diversion, feeling of satiety, eating style, meal contents and temporal eating patterns. The Japanese version of the Morningness–Eveningness (ME) questionnaire was used to measure self-rated preference for the degree to which people prefer to be active in the morning or the evening (ME). Results The scores for meal contents and temporal eating patterns in rotating shift workers were significantly higher than those in day workers. The ME score of rotating shift workers was significantly lower, indicating greater eveningness/less morningness among rotating shift workers. Multivariate linear regression revealed that the ME score was significantly negatively associated with temporal eating patterns and showed a negative association with the score for meal contents at a trend level, while current work shift was not significantly correlated with the scores. Conclusions These results suggest that eating behaviours for rotating shift workers are associated with a more unbalanced diet and abnormal temporal eating patterns and that the associations may be explained by diurnal preference rather than by rotating shift work. PMID:27895063

Circadian rhythm adaptation to simulated night shift work: effect of nocturnal bright-light duration.

PubMed

Eastman, C I; Liu, L; Fogg, L F

1995-07-01

We compared bright-light durations of 6, 3 and 0 hours (i.e. dim light) during simulated night shifts for phase shifting the circadian rectal temperature rhythm to align with a 12-hour shift of the sleep schedule. After 10 baseline days there were 8 consecutive night-work, day-sleep days, with 8-hour sleep (dark) periods. The bright light (about 5,000 lux, around the baseline temperature minimum) was used during all 8 night shifts, and dim light was < 500 lux. This was a field study in which subjects (n = 46) went outside after the night shifts and slept at home. Substantial circadian adaptation (i.e. a large cumulative temperature rhythm phase shift) was produced in many subjects in the bright light groups, but not in the dim light group. Six and 3 hours of bright light were each significantly better than dim light for phase shifting the temperature rhythm, but there was no significant difference between 6 and 3 hours. Thus, durations > 3 hours are probably not necessary in similar shift-work situations. Larger temperature rhythm phase shifts were associated with better subjective daytime sleep, less subjective fatigue and better overall mood.

Health consequences of shift-work: the case of iranian hospital security personnel.

PubMed

Abedini, Roghayeh; Soltanzadeh, Ahmad; Faghih, Mohammad Amin; Mohammadi, Heidar; Kamalinia, Mojtaba; Mohraz, Majid Habibi; Arassi, Maziyar; Veyseh, Peyman Piran; Aghaei, Hamed; Hosseini, Seyed Younes

2015-01-01

Shift-work, which is an ergonomics issue in workplaces, can negatively affect workers. The security personnel of medical centers in Iran have multiple responsibilities and consequently are exposed to such unwanted situations as observing patients, disputing with patient's attendants, unwanted shift schedules, and being away from family for long periods. This study assessed health problems of Iranian hospital security personnel (shift-worker personnel) using the Survey of Shift-workers (SOS) questionnaire (Persian version). This cross-sectional study was conducted in seven medical centers (4 hospitals and 3 clinics). A total of 416 workers were surveyed: shift-workers (exposed group) (n=209) and non-shift-workers (unexposed group) (n=207). The prevalence of adverse health effects was higher in shift-workers than day-workers. The level of education and mean Body Mass Index (BMI) in shift-workers were significantly higher compared with day-workers. The prevalence of gastrointestinal disorders, cardiovascular and psychological problems were also significantly higher in shift-workers compared with day-workers. Overall, the prevalence of health problems among the security personnel of medical centers was high. Hence, it is recommended that personnel be put under periodic monitoring and receive medical counseling and treatment if there is any disorder.

The effect of resident physician stress, burnout, and empathy on patient-centered communication during the long-call shift.

PubMed

Passalacqua, Stacey A; Segrin, Chris

2012-01-01

During the long-call shift medical residents experience a number of stressors that could compromise the quality of care they provide to their patients. The aim of this study was to investigate how perceived stress and burnout affect changes in empathy over the long-call shift and how those changes in empathy are associated with patient-centered communication practices. Residents (n=93) completed self-report measures of stress, burnout, and empathy at the start of their long-call shift and then completed measures of empathy and patient-centered communication at the end of the same shift. There was a significant decline in physician empathy from the beginning to the end of the long-call shift. Perceived stress was significantly associated with higher burnout, which was, in turn, significantly associated with declines in empathy from pre- to posttest. Declines in empathy predicted lower self-reported patient-centered communication during the latter half of the shift. This study suggests that residents who perceive high levels of stress are at risk for burnout and deterioration in empathy toward their patients, both of which may compromise the quality of their interactions with patients.

Effect of Positioning of the ROI on BMD of the Forearm and Its Subregions.

PubMed

Rosen, Elizabeth O; McNamara, Elizabeth A; Whittaker, LaTarsha G; Malabanan, Alan O; Rosen, Harold N

2018-03-21

Inconsistent positioning of patients and region of interest (ROI) is known to influence the precision of bone mineral density (BMD) measurements in the spine and hip. However, it is unknown whether minor shifts in the positioning of the ROI along the shaft of the radius affect the measurement of forearm BMD and its subregions. The ultradistal (UD-), mid-, one-third, and total radius BMDs of 50 consecutive clinical densitometry patients were acquired. At baseline the distal end of the ROI was placed at the tip of the ulnar styloid as usual, and then the forearm was reanalyzed 10 more times, each time shifting the ROI 1 mm proximally. No corrections for multiple comparisons were necessary since the differences that were significant were significant at p < 0.001. The UD-radius BMD increased as the ROI was shifted proximally; the increase was significant when shifted even 1 mm proximally (p < 0.001). These same findings held true for the mid- and total radius bone density, though the percent increase with moving proximally was significantly greater for the UD radius than for the other subregions. However, there was no significant change in the one-third radius BMD when shifted proximally 1-10 mm. Minor proximal shifts of the forearm ROI substantially affect the BMD of the UD-, mid- and total radius, while having no effect on the one-third radius BMD. Since the one-third radius is the only forearm region usually reported, minor proximal shifts of the ROI should not influence forearm BMD results significantly. Copyright © 2018 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Sleep, mental health status, and medical errors among hospital nurses in Japan.

PubMed

Arimura, Mayumi; Imai, Makoto; Okawa, Masako; Fujimura, Toshimasa; Yamada, Naoto

2010-01-01

Medical error involving nurses is a critical issue since nurses' actions will have a direct and often significant effect on the prognosis of their patients. To investigate the significance of nurse health in Japan and its potential impact on patient services, a questionnaire-based survey amongst nurses working in hospitals was conducted, with the specific purpose of examining the relationship between shift work, mental health and self-reported medical errors. Multivariate analysis revealed significant associations between the shift work system, General Health Questionnaire (GHQ) scores and nurse errors: the odds ratios for shift system and GHQ were 2.1 and 1.1, respectively. It was confirmed that both sleep and mental health status among hospital nurses were relatively poor, and that shift work and poor mental health were significant factors contributing to medical errors.

Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures

PubMed Central

Barger, Laura K; Ayas, Najib T; Cade, Brian E; Cronin, John W; Rosner, Bernard; Speizer, Frank E; Czeisler, Charles A

2006-01-01

Background A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States. Methods and Findings We conducted a Web-based survey, across the United States, in which 2,737 residents in their first postgraduate year (interns) completed 17,003 monthly reports. The association between the number of extended-duration shifts worked in the month and the reporting of significant medical errors, preventable adverse events, and attentional failures was assessed using a case-crossover analysis in which each intern acted as his/her own control. Compared to months in which no extended-duration shifts were worked, during months in which between one and four extended-duration shifts and five or more extended-duration shifts were worked, the odds ratios of reporting at least one fatigue-related significant medical error were 3.5 (95% confidence interval [CI], 3.3–3.7) and 7.5 (95% CI, 7.2–7.8), respectively. The respective odds ratios for fatigue-related preventable adverse events, 8.7 (95% CI, 3.4–22) and 7.0 (95% CI, 4.3–11), were also increased. Interns working five or more extended-duration shifts per month reported more attentional failures during lectures, rounds, and clinical activities, including surgery and reported 300% more fatigue-related preventable adverse events resulting in a fatality. Conclusions In our survey, extended-duration work shifts were associated with an increased risk of significant medical errors, adverse events, and attentional failures in interns across the United States. These results have important public policy implications for postgraduate medical education. PMID:17194188

Can sleep quality and burnout affect the job performance of shift-work nurses? A hospital cross-sectional study.

PubMed

Giorgi, Fabio; Mattei, Antonella; Notarnicola, Ippolito; Petrucci, Cristina; Lancia, Loreto

2018-03-01

The aim of this study was to investigate any possible relationship between sleep disorders, burnout and job performance in a shift-work population of nurses. Sleep disorders and burnout can affect the job performance of nurses in terms of efficiency, productivity, task execution speed and supervision, which can be compromised when work shifts are organized on a 24-hour schedule and when the shift itself is irregular. A cross-sectional observational study was conducted from August 2014 - January 2015 on a sample of 315 shift-work nurses across 39 wards in seven central Italian hospitals. The Pittsburgh Sleep Quality Index was used to detect the presence of sleep disorders, the Copenhagen Burnout Inventory was used to detect the presence of any possible type of burnout and the Job Performance Scale was used to measure job performance. Data analysis was mainly based on a multivariate logistic regression to identify variables significantly associated with investigated outcomes. On shift-work nurses' sleep quality and burnout correlated positively. The female gender and personal burnout were significantly associated with impaired sleep quality, while working in the psychiatric setting, working a long cycle shift pattern and experiencing daytime dysfunction were significantly associated with burnout. A significant negative association between patient-related burnout and job performance was observed. Specific characteristics of shift-work nurses can directly affect sleep quality and burnout and indirectly job performance. This evidence offers healthcare administrators opportunities to intervene with measures to promote nurse's health, well-being and safety. © 2017 John Wiley & Sons Ltd.

Shift Schedules and Intern Work Hours, Patient Numbers, Conference Attendance, and Sleep at a Single Pediatric Residency Program.

PubMed

Kocolas, Irene; Day, Kristen; King, Marta; Stevenson, Adam; Sheng, Xiaoming; Hobson, Wendy; Bruse, Jaime; Bale, James

2017-03-01

The effects of 2011 Accreditation Council on Graduate Medical Education (ACGME) duty hour standards on intern work hours, patient load, conference attendance, and sleep have not been fully determined. We prospectively compared intern work hours, patient numbers, conference attendance, sleep duration, pattern, and quality in a 2011 ACGME duty hour-compliant shift schedule with a 2003 ACGME duty hour-compliant call schedule at a single pediatric residency program. Interns were assigned to shift or call schedules during 4 alternate months in the winter of 2010-2011. Work hours, patient numbers, conference attendance, sleep duration, pattern, and quality were tracked. Interns worked significantly fewer hours per week on day (73.2 hours) or night (71.6 hours) shifts than during q4 call (79.6 hours; P < .01). During high census months, shift schedule interns cared for significantly more patients/day (8.1/day shift vs 6.2/call; P < .001) and attended significantly fewer conferences than call schedule interns. Night shift interns slept more hours per 24-hour period than call schedule interns (7.2 ± 0.5 vs 6.3 ± 0.9 hours; P < .05) and had more consistent sleep patterns. A shift schedule resulted in reduced intern work hours and improved sleep duration and pattern. Although intern didactic conference attendance declined significantly during high census months, opportunities for experiential learning remained robust with unchanged or increased intern patient numbers. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Effect of Shift Work on Nocturia.

PubMed

Kim, Jin Wook

2016-01-01

To identify the circadian sensitive component of nocturia by comparing nocturia in patients who voluntarily choose a disrupted circadian rhythm, that is, shift workers, with those who maintain normal day-night cycles. Between 2011 and 2013, a total of 1741 untreated patients, 1376 nonshift workers and 365 shift workers, were compared for nocturia indices based on frequency volume charts (FVCs). General linear model of 8-hour interval urine production and frequency were compared between FVCs of nonshift workers, FVCs of night-shift workers, and FVCs of day-shift workers. Nocturia frequency was increased in the night-shift workers (2.38 ± 1.44) compared with nonshift workers (2.18 ± 1.04) (P <.01). Whereas nocturnal polyuria index did not increase significantly (0.33 ± 0.19 for night-shift workers, 0.34 ± 0.13 for nonshift workers, P = .24), nocturnal bladder capacity index increased significantly (1.41 ± 1.06 for night-shift workers, 1.26 ± 0.92 for nonshift workers, P <.01). Eight-hour interval indices show that urine production changed with shift (P <.01), whereas voiding frequency remains unchanged despite shift changes (P = .35). Patients in alternating work shifts showed increased nocturia, especially during their night shift. These changes tended to be more associated with decreased nocturnal bladder capacity than increased nocturnal polyuria. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of shift duration on the efficacy and tolerability of armodafinil in patients with excessive sleepiness associated with shift work disorder.

PubMed

Harsh, John; Yang, Ronghua; Hull, Steven G

2014-05-01

To examine the impact of night-shift duration (≤9 hours or >9 hours) on efficacy and tolerability of armodafinil in patients with shift work disorder (SWD). This was a post hoc analysis of a 6 week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Shift workers with diagnosed SWD and late-in-shift sleepiness (between 4 am and 8 am, including the commute home) received armodafinil 150 mg or placebo before their night shift. Proportion of patients with at least minimal improvement in late-in-shift sleepiness, late-in-shift Clinical Global Impressions-Change (CGI-C) rating and Karolinska Sleepiness Scale (KSS), as well as overall Global Assessment of Functioning (GAF) scale and modified Sheehan Disability Scale (SDS-M), were assessed at baseline and final visit. Of the 383 patients enrolled, 279 (73%) worked shifts ≤9 hours and 104 (27%) worked shifts >9 hours. A greater percentage of patients receiving armodafinil had at least minimal improvement in late-in-shift CGI-C (≤9 hours: 78% vs 60%, P = 0.0017; >9 hours: 77% vs 46%, P = 0.0020) regardless of shift duration. Armodafinil patients also demonstrated significantly greater improvements in GAF score (≤9 hours: 9.5 vs 5.4, P < 0.0001; >9 hours: 9.6 vs 4.3, P = 0.0019) and KSS score (≤9 hours: -2.9 vs -1.9, P = 0.0002; >9 hours: -2.8 vs -1.6, P = 0.00 28). Improvement in SDS-M composite score was significantly greater for armodafinil patients working >9 hours (-6.8 vs -2.7, P = 0.0086). Headache was the most frequent adverse event in all treatment groups. Patients receiving armodafinil had significantly greater improvements in late-in-shift clinical condition and in wakefulness and overall global functioning than did placebo-treated patients, regardless of shift duration. Prospectively designed, randomized clinical trials that include objective measures of sleepiness are needed to support these findings.

An analysis of clock-shift experiments: is scatter increased and deflection reduced in clock-shifted homing pigeons?

PubMed

Chappell

1997-01-01

Clock-shifting (altering the phase of the internal clock) in homing pigeons leads to a deflection in the vanishing bearing of the clock-shifted group relative to controls. However, two unexplained phenomena are common in clock-shift experiments: the vanishing bearings of the clock-shifted group are often more scattered (with a shorter vector length) than those of the control group, and the deflection of the mean bearing of the clock-shifted group from that of the controls is often smaller than expected theoretically. Here, an analysis of 55 clock-shift experiments performed in four countries over 21 years is reported. The bearings of the clock-shifted groups were significantly more scattered than those of controls and less deflected than expected, but these effects were not significantly different at familiar and unfamiliar sites. The possible causes of the effects are discussed and evaluated with reference to this analysis and other experiments. The most likely causes appear to be conflict between the directions indicated by the sun compass and either unshifted familiar visual landmarks (at familiar sites only) or the unshifted magnetic compass (possible at both familiar and unfamiliar sites).

Effect of Phase Shift from Corals to Zoantharia on Reef Fish Assemblages

PubMed Central

Cruz, Igor C. S.; Loiola, Miguel; Albuquerque, Tiago; Reis, Rodrigo; de Anchieta C. C. Nunes, José; Reimer, James D.; Mizuyama, Masaru; Kikuchi, Ruy K. P.; Creed, Joel C.

2015-01-01

Consequences of reef phase shifts on fish communities remain poorly understood. Studies on the causes, effects and consequences of phase shifts on reef fish communities have only been considered for coral-to-macroalgae shifts. Therefore, there is a large information gap regarding the consequences of novel phase shifts and how these kinds of phase shifts impact on fish assemblages. This study aimed to compare the fish assemblages on reefs under normal conditions (relatively high cover of corals) to those which have shifted to a dominance of the zoantharian Palythoa cf. variabilis on coral reefs in Todos os Santos Bay (TSB), Brazilian eastern coast. We examined eight reefs, where we estimated cover of corals and P. cf. variabilis and coral reef fish richness, abundance and body size. Fish richness differed significantly between normal reefs (48 species) and phase-shift reefs (38 species), a 20% reduction in species. However there was no difference in fish abundance between normal and phase shift reefs. One fish species, Chaetodon striatus, was significantly less abundant on normal reefs. The differences in fish assemblages between different reef phases was due to differences in trophic groups of fish; on normal reefs carnivorous fishes were more abundant, while on phase shift reefs mobile invertivores dominated. PMID:25629532

No first night shift effect observed following a nocturnal main sleep and a prophylactic 1-h afternoon nap.

PubMed

Kosmadopoulos, Anastasi; Zhou, Xuan; Roach, Gregory D; Darwent, David; Sargent, Charli

Neurobehavioural impairment on the first night shift is often greater than on subsequent night shifts due to extended wakefulness. The aim of the study was to determine whether a 1-h afternoon nap prior to the first night shift is sufficient to produce neurobehavioural performance at levels comparable to the second night shift. Twelve male volunteers (mean age 22.9 years) participated in a laboratory protocol that simulated two 12-h night shifts. A nap preceded the first shift and a 7-h daytime sleep was scheduled between shifts. Neurobehavioural performance and subjective sleepiness measured across each night did not significantly differ between first and second shifts.

Midlatitude Cloud Shifts, Their Primary Link to the Hadley Cell, and Their Diverse Radiative Effects

NASA Technical Reports Server (NTRS)

Tselioudis, George; Lipat, Bernard R.; Konsta, Dimitra; Grise, Kevin M.; Polvani, Lorenzo M.

2016-01-01

We investigate the interannual relationship among clouds, their radiative effects, and two key indices of the atmospheric circulation: the latitudinal positions of the Hadley cell edge and the midlatitude jet. From reanalysis data and satellite observations, we find a clear and consistent relationship between the width of the Hadley cell and the high cloud field, statistically significant in nearly all regions and seasons. In contrast, shifts of the midlatitude jet correlate significantly with high cloud shifts only in the North Atlantic region during the winter season. While in that region and season poleward high cloud shifts are associated with shortwave radiative warming, over the Southern Oceans during all seasons they are associated with shortwave radiative cooling. Finally, a trend analysis reveals that poleward high cloud shifts observed over the 1983-2009 period are more likely related to Hadley cell expansion, rather than poleward shifts of the midlatitude jets.

The impact of night-shift work on platelet function in healthy medical staff.

PubMed

Nakao, Tomoko; Yasumoto, Atsushi; Tokuoka, Suzumi; Kita, Yoshihiro; Kawahara, Takuya; Daimon, Masao; Yatomi, Yutaka

2018-04-18

Rotating shift work has been reported to increase the risk of cardiovascular diseases. Vascular endothelial dysfunction and platelet activation are among the leading causes of thrombus formation in patients with myocardial infarction or stroke. Endothelial function has been shown to be impaired immediately after night-shift work; however, it is not known whether platelets are also activated. The aim of this study was to investigate the acute impact of night-shift work on platelet function. This observational study included 11 healthy medical staff members (seven women, median age 32 years). We examined each subject's platelet aggregation rates and the serum concentrations of eicosanoid mediators after night-shift work and on day-shift work without preceding night-shift work (baseline). Platelet aggregation did not differ from baseline levels after night-shift work. However, serum cyclooxygenase (COX)-metabolized eicosanoid mediators, particularly thromboxane (Tx) B 2 (a stable metabolite of TxA 2 and the most important marker of platelet activation), were significantly higher after the night-shift than at baseline (median 65.3 vs 180.4 ng/ml). Although platelet aggregation did not increase, there was an increase in serum COX-metabolized eicosanoid mediators such as TxB 2 in healthy medical staff after night-shift work. This platelet hypersensitivity may be one of the mechanisms underlying the significant association between night-shift work and adverse cardiovascular outcomes.

Referential shift in Nicaraguan Sign Language: a transition from lexical to spatial devices

PubMed Central

Kocab, Annemarie; Pyers, Jennie; Senghas, Ann

2015-01-01

Even the simplest narratives combine multiple strands of information, integrating different characters and their actions by expressing multiple perspectives of events. We examined the emergence of referential shift devices, which indicate changes among these perspectives, in Nicaraguan Sign Language (NSL). Sign languages, like spoken languages, mark referential shift grammatically with a shift in deictic perspective. In addition, sign languages can mark the shift with a point or a movement of the body to a specified spatial location in the three-dimensional space in front of the signer, capitalizing on the spatial affordances of the manual modality. We asked whether the use of space to mark referential shift emerges early in a new sign language by comparing the first two age cohorts of deaf signers of NSL. Eight first-cohort signers and 10 second-cohort signers watched video vignettes and described them in NSL. Narratives were coded for lexical (use of words) and spatial (use of signing space) devices. Although the cohorts did not differ significantly in the number of perspectives represented, second-cohort signers used referential shift devices to explicitly mark a shift in perspective in more of their narratives. Furthermore, while there was no significant difference between cohorts in the use of non-spatial, lexical devices, there was a difference in spatial devices, with second-cohort signers using them in significantly more of their narratives. This suggests that spatial devices have only recently increased as systematic markers of referential shift. Spatial referential shift devices may have emerged more slowly because they depend on the establishment of fundamental spatial conventions in the language. While the modality of sign languages can ultimately engender the syntactic use of three-dimensional space, we propose that a language must first develop systematic spatial distinctions before harnessing space for grammatical functions. PMID:25713541

Referential shift in Nicaraguan Sign Language: a transition from lexical to spatial devices.

PubMed

Kocab, Annemarie; Pyers, Jennie; Senghas, Ann

2014-01-01

Even the simplest narratives combine multiple strands of information, integrating different characters and their actions by expressing multiple perspectives of events. We examined the emergence of referential shift devices, which indicate changes among these perspectives, in Nicaraguan Sign Language (NSL). Sign languages, like spoken languages, mark referential shift grammatically with a shift in deictic perspective. In addition, sign languages can mark the shift with a point or a movement of the body to a specified spatial location in the three-dimensional space in front of the signer, capitalizing on the spatial affordances of the manual modality. We asked whether the use of space to mark referential shift emerges early in a new sign language by comparing the first two age cohorts of deaf signers of NSL. Eight first-cohort signers and 10 second-cohort signers watched video vignettes and described them in NSL. Narratives were coded for lexical (use of words) and spatial (use of signing space) devices. Although the cohorts did not differ significantly in the number of perspectives represented, second-cohort signers used referential shift devices to explicitly mark a shift in perspective in more of their narratives. Furthermore, while there was no significant difference between cohorts in the use of non-spatial, lexical devices, there was a difference in spatial devices, with second-cohort signers using them in significantly more of their narratives. This suggests that spatial devices have only recently increased as systematic markers of referential shift. Spatial referential shift devices may have emerged more slowly because they depend on the establishment of fundamental spatial conventions in the language. While the modality of sign languages can ultimately engender the syntactic use of three-dimensional space, we propose that a language must first develop systematic spatial distinctions before harnessing space for grammatical functions.

Integral cross sections for the direct excitation of the A 3 (sigma) u +, B 3 (pi) g, W 3 (delta) u, B' 3 (sigma) u -, a' 1 (sigma) u -, a 1 (pi) g, w 1 (delta) u, and C 3 (pi) u electronic states in

NASA Technical Reports Server (NTRS)

Johnson, P. V.; Malone, C. P.; Kanik, I.

2005-01-01

Integral cross sections for electron impact excitation out of the ground state (X 1(sigma)g +) to the A 3(sigma)u +, B 3(pi)g, W 3(delta)u, B' 3(sigma)u -, a' 1(sigma)u -, a 1(pi)g, w 1(delta)u, and states in N2 are reported at incident energies ranging between 10 and 100 eV. These data have been derived by integrating differential cross sections previously reported by this group. New differential cross section measurements for the a 1(pi)g state at 200 eV are also presented to extend the range of the reported integral cross sections for this state, which is responsible for the emissions of the Lyman-Birge-Hopfield band system (a 1(pi)g (rightwards arrow) X 1(sigma)g +). The present results are compared and critically evaluated against existing cross sec In general, the present cross sections are smaller than previous results at low impact energies from threshold through the excitation function peak regions. These lower cross sections have potentially significant implications on our understanding of UV emissions in the atmospheres of Earth and Titan.

Isolation and characterization of the genes for two small RNAs of herpesvirus papio and their comparison with Epstein-Barr virus-encoded EBER RNAs.

PubMed Central

Howe, J G; Shu, M D

1988-01-01

Genes for the Epstein-Barr virus-encoded RNAs (EBERs), two low-molecular-weight RNAs encoded by the human gammaherpesvirus Epstein-Barr virus (EBV), hybridize to two small RNAs in a baboon cell line that contains a similar virus, herpesvirus papio (HVP). The genes for the HVP RNAs (HVP-1 and HVP-2) are located together in the small unique region at the left end of the viral genome and are transcribed by RNA polymerase III in a rightward direction, similar to the EBERs. There is significant similarity between EBER1 and HVP-1 RNA, except for an insert of 22 nucleotides which increases the length of HVP-1 RNA to 190 nucleotides. There is less similarity between the sequences of EBER2 and HVP-2 RNA, but both have a length of about 170 nucleotides. The predicted secondary structure of each HVP RNA is remarkably similar to that of the respective EBER, implying that the secondary structures are important for function. Upstream from the initiation sites of all four RNA genes are several highly conserved sequences which may function in the regulation of transcription. The HVP RNAs, together with the EBERs, are highly abundant in transformed cells and are efficiently bound by the cellular La protein. Images PMID:2839701

Oral contraceptive therapy modulates hemispheric asymmetry in spatial attention.

PubMed

Cicinelli, Ettore; De Tommaso, Marina; Cianci, Antonio; Colacurci, Nicola; Rella, Leonarda; Loiudice, Luisa; Cicinelli, Maria Vittoria; Livrea, Paolo

2011-12-01

Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The visual line-bisection task administered to normally cycling women showed different patterns of the interhemispheric interactions during menses and the midluteal cycle phase. However, the contribution of estrogens and progestins hormones to this phenomenon is still unclear. The aim of our study was to show a variation of FCAs in women administered oral contraceptives (OCs) using the visual line-bisection task. Visual line-bisection task with three horizontal lines was administered to 36 healthy women taking a 21-day OC. Twenty-nine patients were right handed. The task was administered during OC intake (day 10) and at the end of the pill-free period. The right-handed women showed a significant leftward bias of veridical center on the first and third lines during OC intake compared with an opposite rightward bias during the pill-free period. The same phenomenon of contralateral deviation was observed in left-handed women on day 10 of OC intake. The results of this study confirm a hormonal modulation on interhemispheric interaction and suggest that OCs may improve the interhemispheric interaction reducing FCAs compared with the low hormone level period. This opens new insights in OC prescription and choice of administration schedule in order to improve cognitive performances. Copyright © 2011 Elsevier Inc. All rights reserved.

The contribution of collective attack tactics in differentiating handball score efficiency.

PubMed

Rogulj, Nenad; Srhoj, Vatromir; Srhoj, Ljerka

2004-12-01

The prevalence of 19 elements of collective tactics in score efficient and score inefficient teams was analyzed in 90 First Croatian Handball League--Men games during the 1998-1999 season. Prediction variables were used to describe duration, continuity, system, organization and spatial direction of attacks. Analysis of the basic descriptive and distribution statistical parameters revealed normal distribution of all variables and possibility to use multivariate methods. Canonic discrimination analysis and analysis of variance showed the use of collective tactics elements on attacks to differ statistically significantly between the winning and losing teams. Counter-attacks and uninterrupted attacks predominate in winning teams. Other types of attacks such as long position attack, multiply interrupted attack, attack with one circle runner attack player/pivot, attack based on basic principles, attack based on group cooperation, attack based on independent action, attack based on group maneuvering, rightward directed attack and leftward directed attack predominate in losing teams. Winning teams were found to be clearly characterized by quick attacks against unorganized defense, whereas prolonged, interrupted position attacks against organized defense along with frequent and diverse tactical actions were characteristic of losing teams. The choice and frequency of using a particular tactical activity in position attack do not warrant score efficiency but usually are consequential to the limited anthropologic potential and low level of individual technical-tactical skills of the players in low-quality teams.

Epstein-Barr virus miR-BART20-5p regulates cell proliferation and apoptosis by targeting BAD.

PubMed

Kim, Hyoji; Choi, Hoyun; Lee, Suk Kyeong

2015-01-28

Although Epstein-Barr virus (EBV) BamHI A rightward transcript (BART) microRNAs (miRNAs) are ubiquitously expressed in EBV-associated tumors, the role of most BART miRNAs is unclear. In this study, we showed that Bcl-2-associated death promoter (BAD) expression was significantly lower in EBV-infected AGS-EBV cells than in EBV-negative AGS cells and investigated whether BART miRNAs target BAD. Using bioinformatics analysis, five BART miRNAs showing seed match with the 3' untranslated region (3'-UTR) of BAD were selected. Of these, only miR-BART20-5p reduced BAD expression when individually transfected into AGS cells. A luciferase assay revealed that miR-BART20-5p directly targets BAD. The expression of BAD mRNA and protein was decreased by miR-BART20-5p and increased by an inhibitor of miR-BART20-5p. PE-Annexin V staining and cell proliferation assays showed that miR-BART20-5p reduced apoptosis and enhanced cell growth. Furthermore, miR-BART20-5p increased chemoresistance to 5-fluorouracil and docetaxel. Our data suggest that miR-BART20-5p contributes to tumorigenesis of EBV-associated gastric carcinoma by directly targeting the 3'-UTR of BAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Associations of rotational shift work and night shift status with hypertension: a systematic review and meta-analysis.

PubMed

Manohar, Sandhya; Thongprayoon, Charat; Cheungpasitporn, Wisit; Mao, Michael A; Herrmann, Sandra M

2017-10-01

The reported risks of hypertension (HTN) in rotating shift and night shift workers are controversial. The objective of this meta-analysis was to assess the association between shift work status and HTN. A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through October 2016. Studies that reported odds ratios (OR) comparing the risk of HTN in shift workers were included. A prespecified subgroup analysis by rotating shift and night shift statuses were also performed. Pooled OR and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The protocol for this study is registered with International Prospective Register of Systematic Reviews; no. CRD42016051843. Twenty-seven observational studies (nine cohort and 18 cross-sectional studies) with a total of 394 793 individuals were enrolled. The pooled ORs of HTN in shift workers in cohort and cross-sectional studies were 1.31 (95% CI, 1.07-1.60) and 1.10 (95% CI, 1.00-1.20), respectively. When meta-analysis was restricted only to cohort studies in rotating shift, the pooled OR of HTN in rotating shift workers was 1.34 (95% CI, 1.08-1.67). The data regarding night shift and HTN in cohort studies was limited. The pooled OR of HTN in night shift workers in cross-sectional studies was 1.07 (95% CI, 0.85-1.35). Based on the findings of our meta-analysis, shiftwork status may play an important role in HTN, as there is a significant association between rotating shift work and HTN. However, there is no significant association between night shift status and risk of HTN.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

PubMed

Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

Shift work in nursing: is it really a risk factor for nurses' health and patients' safety?

PubMed

Admi, Hanna; Tzischinsky, Orna; Epstein, Rachel; Herer, Paula; Lavie, Peretz

2008-01-01

There is evidence in the scientific literature of the adverse physiological and psychological effects of shift work, including disruption to biological rhythm, sleep disorders, health problems, diminished performance at work, job dissatisfaction, and social isolation. In this study, the results of health problems and sleep disorders between female and male nurses, between daytime and shift nurses, and between sleep-adjusted and non-sleep-adjusted shift nurses were compared. Also the relationship between adjustment to shift work and organizational outcomes (errors and incidents and absenteeism from work) was analyzed. Gender, age, and weight were more significant factors than shift work in determining the well-being of nurses. Shift work by itself was not found to be a risk factor for nurses' health and organizational outcomes in this study. Moreover, nurses who were identified as being "non-adaptive" to shift work were found to work as effectively and safely as their adaptive colleagues in terms of absenteeism from work and involvement in professional errors and accidents. This research adds two additional findings to the field of shift work studies. The first finding is that female shift workers complain significantly more about sleep disorders than male shift workers. Second, although high rates of nurses whose sleep was not adapted to shift work were found, this did not have a more adverse impact on their health, absenteeism rates, or performance (reported errors and incidents), compared to their "adaptive" and "daytime" colleagues.

Self-Reported Recovery from 2-Week 12-Hour Shift Work Schedules: A 14-Day Follow-Up.

PubMed

Merkus, Suzanne L; Holte, Kari Anne; Huysmans, Maaike A; van de Ven, Peter M; van Mechelen, Willem; van der Beek, Allard J

2015-09-01

Recovery from fatigue is important in maintaining night workers' health. This study compared the course of self-reported recovery after 2-week 12-hour schedules consisting of either night shifts or swing shifts (i.e., 7 night shifts followed by 7 day shifts) to such schedules consisting of only day work. Sixty-one male offshore employees-20 night workers, 16 swing shift workers, and 25 day workers-rated six questions on fatigue (sleep quality, feeling rested, physical and mental fatigue, and energy levels; scale 1-11) for 14 days after an offshore tour. After the two night-work schedules, differences on the 1(st) day (main effects) and differences during the follow-up (interaction effects) were compared to day work with generalized estimating equations analysis. After adjustment for confounders, significant main effects were found for sleep quality for night workers (1.41, 95% confidence interval 1.05-1.89) and swing shift workers (1.42, 95% confidence interval 1.03-1.94) when compared to day workers; their interaction terms were not statistically significant. For the remaining fatigue outcomes, no statistically significant main or interaction effects were found. After 2-week 12-hour night and swing shifts, only the course for sleep quality differed from that of day work. Sleep quality was poorer for night and swing shift workers on the 1(st) day off and remained poorer for the 14-day follow-up. This showed that while working at night had no effect on feeling rested, tiredness, and energy levels, it had a relatively long-lasting effect on sleep quality.

Differential relationships between set-shifting abilities and dimensions of insight in schizophrenia.

PubMed

Diez-Martin, J; Moreno-Ortega, M; Bagney, A; Rodriguez-Jimenez, R; Padilla-Torres, D; Sanchez-Morla, E M; Santos, J L; Palomo, T; Jimenez-Arriero, M A

2014-01-01

To assess insight in a large sample of patients with schizophrenia and to study its relationship with set shifting as an executive function. The insight of a sample of 161 clinically stable, community-dwelling patients with schizophrenia was evaluated by means of the Scale to Assess Unawareness of Mental Disorder (SUMD). Set shifting was measured using the Trail-Making Test time required to complete part B minus the time required to complete part A (TMT B-A). Linear regression analyses were performed to investigate the relationships of TMT B-A with different dimensions of general insight. Regression analyses revealed a significant association between TMT B-A and two of the SUMD general components: 'awareness of mental disorder' and 'awareness of the efficacy of treatment'. The 'awareness of social consequences' component was not significantly associated with set shifting. Our results show a significant relation between set shifting and insight, but not in the same manner for the different components of the SUMD general score. Copyright © 2013 S. Karger AG, Basel.

Improving robustness against electrode shift of high density EMG for myoelectric control through common spatial patterns.

PubMed

Pan, Lizhi; Zhang, Dingguo; Jiang, Ning; Sheng, Xinjun; Zhu, Xiangyang

2015-12-02

Most prosthetic myoelectric control studies have concentrated on low density (less than 16 electrodes, LD) electromyography (EMG) signals, due to its better clinical applicability and low computation complexity compared with high density (more than 16 electrodes, HD) EMG signals. Since HD EMG electrodes have been developed more conveniently to wear with respect to the previous versions recently, HD EMG signals become an alternative for myoelectric prostheses. The electrode shift, which may occur during repositioning or donning/doffing of the prosthetic socket, is one of the main reasons for degradation in classification accuracy (CA). HD EMG signals acquired from the forearm of the subjects were used for pattern recognition-based myoelectric control in this study. Multiclass common spatial patterns (CSP) with two types of schemes, namely one versus one (CSP-OvO) and one versus rest (CSP-OvR), were used for feature extraction to improve the robustness against electrode shift for myoelectric control. Shift transversal (ST1 and ST2) and longitudinal (SL1 and SL2) to the direction of the muscle fibers were taken into consideration. We tested nine intact-limb subjects for eleven hand and wrist motions. The CSP features (CSP-OvO and CSP-OvR) were compared with three commonly used features, namely time-domain (TD) features, time-domain autoregressive (TDAR) features and variogram (Variog) features. Compared with the TD features, the CSP features significantly improved the CA over 10 % in all shift configurations (ST1, ST2, SL1 and SL2). Compared with the TDAR features, a. the CSP-OvO feature significantly improved the average CA over 5 % in all shift configurations; b. the CSP-OvR feature significantly improved the average CA in shift configurations ST1, SL1 and SL2. Compared with the Variog features, the CSP features significantly improved the average CA in longitudinal shift configurations (SL1 and SL2). The results demonstrated that the CSP features significantly improved the robustness against electrode shift for myoelectric control with respect to the commonly used features.

Heart rate variability changes in business process outsourcing employees working in shifts.

PubMed

Kunikullaya, Kirthana U; Kirthi, Suresh K; Venkatesh, D; Goturu, Jaisri

2010-10-31

Irregular and poor quality sleep is common in business process outsourcing (BPO) employees due to continuous shift working. The influence of this on the cardiac autonomic activity was investigated by the spectral analysis of heart rate variability (HRV). 36 night shift BPO employees (working from 22:00 to 06:00h) and 36 age and sex matched day shift BPO employees (working from 08:00 to 16:00h) were recruited for the study. Five minute electrocardiogram (ECG) was recorded in all the subjects. Heart rate variability was analyzed by fast Fourier transformation using RMS Vagus HRV software. The results were analyzed using Mann Whitney U test, Student t-test, Wilcoxon signed rank test and were expressed as mean ± SD. Sleepiness was significantly higher among night shift workers as measured by Epworth Sleepiness Scale (p<0.001). Night shift BPO employees were found to have a trend towards lower values of vagal parameters - HF power (ms(2)), and higher values of sympathovagal parameters like LF Power (ms(2)) and the LF/HF power (%) suggesting decreased vagal activity and sympathetic over activity, when compared to day shift employees. However, HRV parameters did not vary significantly between the day shift employees and night shift workers baseline values, and also within the night shift group. Night shift working increased the heart rate and shifted the sympathovagal balance towards sympathetic dominance and decreased vagal parameters of HRV. This is an indicator of unfavorable change in the myocardial system, and thus shows increased risk of cardiovascular disease among the night shift employees.

Circadian Disruptions of Heart Rate Variability among Weekly Consecutive-12-hour 2 Shift Workers in the Automobile Factory in Korea.

PubMed

Son, Mia; Sung, Juhon; Yum, Myunggul; Kong, Jung Ok; Lee, Hye Un; Kim, In A; Kim, Jung Yeon

2004-05-01

The objective of this study is to compare the circadian patterns of heart rate variability assessed by 24-hour ambulatory electrocardiographic (ECG) recordings during day shift and night shift among the workers in the 5 days-concecutive- 12-hour shift in an automobile factory in Korea. The study population consisted 300 workers, who were randomly selected among the 8700 total workers in one car factory. To analyse circadian variation, the 24-hour ECG recordings (Marquette) were measured during day shift (08: 00-20: 00 h) and night shift (20: 00-08: 00 h). Analysis was performed for all time and frequency domain measures of HRV. 233 workers completed taking 24-hour ECG recordings. This study shows that the 24 hourcircadian variation mainly follows work/sleep cycle rather than day/night cycle among shift workers. This study also shows that among the night shift, the circadian variation between work and sleep cycle decreased compared to the work/sleep cycle among day shift workers. All time and frequency domain parameters (except LF/HF ratio) show significantly different between work and sleep in the day shift and night shift. These changes in heart rate variability circadian rhythms reflect significant reductions in cardiac parasympathetic activity with the most marked reduction in normal vagal activity among the shift workers. Especially, it suggests the circadian rhytm has blunted among the night workers. The quantification of the circadian variation in HRV can be a surrogates of workers' potential health risk, as well as suggests possible mechanisms through which the shift works compromise workers' health.

Association of eating behaviours with diurnal preference and rotating shift work in Japanese female nurses: a cross-sectional study.

PubMed

Yoshizaki, Takahiro; Kawano, Yukari; Noguchi, Osamu; Onishi, Junko; Teramoto, Reiko; Sunami, Ayaka; Yokoyama, Yuri; Tada, Yuki; Hida, Azumi; Togo, Fumiharu

2016-11-28

Our study examines differences in eating behaviour between day workers and rotating shift workers, and considers whether diurnal preference could explain the differences. Japanese female nurses were studied (39 day workers and 123 rotating shift workers, aged 21-63 years) using self-administered questionnaires. The questionnaires assessed eating behaviours, diurnal preference and demographic characteristics. The questionnaire in the Guidelines for the management of obesity disease issued by the Japan Society for the Study of Obesity was used to obtain scores for the levels of obesity-related eating behaviours, including cognition of constitution, motivation for eating, eating as a diversion, feeling of satiety, eating style, meal contents and temporal eating patterns. The Japanese version of the Morningness-Eveningness (ME) questionnaire was used to measure self-rated preference for the degree to which people prefer to be active in the morning or the evening (ME). The scores for meal contents and temporal eating patterns in rotating shift workers were significantly higher than those in day workers. The ME score of rotating shift workers was significantly lower, indicating greater eveningness/less morningness among rotating shift workers. Multivariate linear regression revealed that the ME score was significantly negatively associated with temporal eating patterns and showed a negative association with the score for meal contents at a trend level, while current work shift was not significantly correlated with the scores. These results suggest that eating behaviours for rotating shift workers are associated with a more unbalanced diet and abnormal temporal eating patterns and that the associations may be explained by diurnal preference rather than by rotating shift work. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Large deviations in the random sieve

NASA Astrophysics Data System (ADS)

Grimmett, Geoffrey

1997-05-01

The proportion [rho]k of gaps with length k between square-free numbers is shown to satisfy log[rho]k=[minus sign](1+o(1))(6/[pi]2) klogk as k[rightward arrow][infty infinity]. Such asymptotics are consistent with Erdos's challenge to prove that the gap following the square-free number t is smaller than clogt/log logt, for all t and some constant c satisfying c>[pi]2/12. The results of this paper are achieved by studying the probabilities of large deviations in a certain ‘random sieve’, for which the proportions [rho]k have representations as probabilities. The asymptotic form of [rho]k may be obtained in situations of greater generality, when the squared primes are replaced by an arbitrary sequence (sr) of relatively prime integers satisfying [sum L: summation operator]r1/sr<[infty infinity], subject to two further conditions of regularity on this sequence.

Asymmetric otolith function and increased susceptibility to motion sickness during exposure to variations in gravitoinertial acceleration level

NASA Technical Reports Server (NTRS)

Lackner, James R.; Graybiel, Ashton; Johnson, Walter H.; Money, Kenneth E.

1987-01-01

Von Baumgarten and coworkers (1979, 1981) have suggested that asymmetries in otolith function between the left and right labyrinths may result from differences in otoconial mass and could play a role in space motion sickness. Such asymmetries would be centrally compensated for under terrestrial conditions, but on exposure to weightlessness the persisting central compensation would produce a central imbalance that could lead to motion sickness. In this work ocular counterrolling was used as a way of measuring the relative 'efficiency' of the left and right otoliths; the ocular counterrolling scores of individuals were compared with their susceptibility to motion sickness during passive exposure to variations in Gz in parabolic flight maneuvers. The experimental findings indicate that large asymmetries in counterrolling for leftward and rightward body tilts are associated with greater susceptibility to motion sickness in parabolic flight.

Effector identity and orthogonal stimulus-response compatibility in blindness to response-compatible stimuli.

PubMed

Nishimura, Akio; Yokosawa, Kazuhiko

2010-03-01

Perceiving a visual stimulus is hampered when the stimulus is compatible with simultaneously prepared or executed action (blindness effect). We explored the roles of the effector identity of the responding hand and of orthogonal compatibility (above-right/below-left correspondence) in the blindness effect. In Experiment 1, participants conducted bimanual key presses with vertically arranged responses while perceiving a brief presentation of rightward or leftward arrowheads. A blindness effect based on the effector identity did emerge, but only with the above-right/below-left key-hand arrangement. An orthogonal blindness effect was not found in Experiment 2 with a horizontal key-press action task and a vertical arrowhead perception task. We concluded that the anatomical identity of the responding hand was not integrated into the action plan with an orthogonally incompatible key-hand arrangement. The findings are discussed in terms of the generality and limits of the blindness effect, and hierarchical response coding.

The role of verbal memory in regressions during reading.

PubMed

Guérard, Katherine; Saint-Aubin, Jean; Maltais, Marilyne

2013-01-01

During reading, participants generally move their eyes rightward on the line. A number of eye movements, called regressions, are made leftward, to words that have already been fixated. In the present study, we investigated the role of verbal memory during regressions. In Experiment 1, participants were asked to read sentences for comprehension. After reading, they were asked to make a regression to a target word presented auditorily. The results revealed that their regressions were guided by memory, as they differed from those of a control group who did not read the sentences. The role of verbal memory during regressions was then investigated by combining the reading task with articulatory suppression (Exps. 2 and 3). The results showed that articulatory suppression affected the size and the accuracy of the initial regression but had a minimal effect on corrective saccades. This suggests that verbal memory plays an important role in determining the location of the initial saccade during regressions.

Trunk- and head-centred spatial coordinates do not affect free-viewing perceptual asymmetries.

PubMed

Nicholls, Michael E R; Mattingley, Jason B; Bradshaw, John L; Krins, Phillip W

2003-11-01

Turning the trunk or head to the left can reduce the severity of leftward neglect. This study sought to determine whether turning the trunk or head to the right would reduce pseudoneglect: A phenomenon where normal participants underestimate the rightward features of a stimulus. Participants made luminance judgements of two mirror-reversed greyscales stimuli. A preference for selecting the stimulus dark on the left was found. The effect of trunk-centred coordinates was examined in Expt. 1 by facing the head toward the display and turning the trunk to the left, right or toward the display. Head-centred coordinates were examined in Expt. 2 by directing the eyes toward the display and then turning the head and trunk. No effect of rotation was observed. It was concluded that the leftward bias for the greyscales task could be based on an object-centred attentional bias or left-to-right eye scanning habits.

Night work and health status of nurses and midwives. cross-sectional study.

PubMed

Burdelak, Weronika; Bukowska, Agnieszka; Krysicka, Jolanta; Pepłońska, Beata

2012-01-01

The aim of this study was to assess the association between night shift work and the prevalence of diseases and conditions among nurses and midwives. The study included 725 subjects (354 working on night shifts and 371 working only during the day). The data were collected via an interview based on the "Standard Shiftwork Index". We analyzed the frequency of diseases and conditions and the relative risk expressed as the odds ratio (adjusted for important confounding factors). The most common diseases in the study population were chronic back pain (47.2%), hypertension (24.5%) and thyroid diseases (21.2%). We found no statistically significant increased relative risk of any diseases and conditions among the night shift nurses, compared to the day shift ones. The duration of the work performed on night shifts was significantly associated with the relative risk of thyroid diseases--increased almost two times in the women working for 15 or more years in such system (p for trend: 0.031). The analysis showed the significantly increased (more than eight times higher) relative risk of feet swelling in the women with 8 or more night duties per month, compared to the women having fewer night shifts. We did not observe a higher frequency of diseases in the night shift nurses, compared to the day shift nurses. These results may be related to the so-called "Healthy Worker Effect". There is a need for further long-term observational studies in the populations of nurses.

The generation and gender shifts in medicine: an exploratory survey of internal medicine physicians.

PubMed

Jovic, Emily; Wallace, Jean E; Lemaire, Jane

2006-05-05

Two striking demographic shifts evident in today's workforce are also apparent in the medical profession. One is the entry of a new generation of physicians, Gen Xers, and the other is the influx of women. Both shifts are argued to have significant implications for recruitment and retention because of assumptions regarding the younger generation's and women's attitudes towards work and patient care. This paper explores two questions regarding the generations: (1) How do Baby Boomer and Generation X physicians perceive the generation shift in work attitudes and behaviours? and (2) Do Baby Boomer and Generation X physicians differ significantly in their work hours and work attitudes regarding patient care and life balance? Gen Xers include those born between 1965 and 1980; Baby Boomers are those born between 1945 and 1964. We also ask: Do female and male Generation X physicians differ significantly in their work hours and work attitudes regarding patient care and life balance? We conducted exploratory interviews with 54 physicians and residents from the Department of Medicine (response rate 91%) and asked about their perceptions regarding the generation and gender shifts in medicine. We limit the analyses to interview responses of 34 Baby Boomers and 18 Generation Xers. We also sent questionnaires to Department members (response rate 66%), and this analysis is limited to 87 Baby Boomers' and 65 Generation Xers' responses. The qualitative interview data suggest significant generation and gender shifts in physicians' attitudes. Baby Boomers generally view Gen Xer physicians as less committed to their medical careers. The quantitative questionnaire data suggest that there are few significant differences in the generations' and genders' reports of work-life balance, work hours and attitudes towards patient care. A combined qualitative and quantitative approach to the generation shift and gender shift in medicine is helpful in revealing that the widely held assumptions are not necessarily reflective of any significant differences in actual work attitudes or behaviours of Boomer and Gen X physicians or of the younger generation of women entering medicine.

The generation and gender shifts in medicine: an exploratory survey of internal medicine physicians

PubMed Central

Jovic, Emily; Wallace, Jean E; Lemaire, Jane

2006-01-01

Background Two striking demographic shifts evident in today's workforce are also apparent in the medical profession. One is the entry of a new generation of physicians, Gen Xers, and the other is the influx of women. Both shifts are argued to have significant implications for recruitment and retention because of assumptions regarding the younger generation's and women's attitudes towards work and patient care. This paper explores two questions regarding the generations: (1) How do Baby Boomer and Generation X physicians perceive the generation shift in work attitudes and behaviours? and (2) Do Baby Boomer and Generation X physicians differ significantly in their work hours and work attitudes regarding patient care and life balance? Gen Xers include those born between 1965 and 1980; Baby Boomers are those born between 1945 and 1964. We also ask: Do female and male Generation X physicians differ significantly in their work hours and work attitudes regarding patient care and life balance? Methods We conducted exploratory interviews with 54 physicians and residents from the Department of Medicine (response rate 91%) and asked about their perceptions regarding the generation and gender shifts in medicine. We limit the analyses to interview responses of 34 Baby Boomers and 18 Generation Xers. We also sent questionnaires to Department members (response rate 66%), and this analysis is limited to 87 Baby Boomers' and 65 Generation Xers' responses. Results The qualitative interview data suggest significant generation and gender shifts in physicians' attitudes. Baby Boomers generally view Gen Xer physicians as less committed to their medical careers. The quantitative questionnaire data suggest that there are few significant differences in the generations' and genders' reports of work-life balance, work hours and attitudes towards patient care. Conclusion A combined qualitative and quantitative approach to the generation shift and gender shift in medicine is helpful in revealing that the widely held assumptions are not necessarily reflective of any significant differences in actual work attitudes or behaviours of Boomer and Gen X physicians or of the younger generation of women entering medicine. PMID:16677387

Effects of Napping During Shift Work on Sleepiness and Performance in Emergency Medical Services Personnel and Similar Shift Workers: A Systematic Review and Meta-Analysis.

PubMed

Martin-Gill, Christian; Barger, Laura K; Moore, Charity G; Higgins, J Stephen; Teasley, Ellen M; Weiss, Patricia M; Condle, Joseph P; Flickinger, Katharyn L; Coppler, Patrick J; Sequeira, Denisse J; Divecha, Ayushi A; Matthews, Margaret E; Lang, Eddy S; Patterson, P Daniel

2018-02-15

Scheduled napping during work shifts may be an effective way to mitigate fatigue-related risk. This study aimed to critically review and synthesize existing literature on the impact of scheduled naps on fatigue-related outcomes for EMS personnel and similar shift worker groups. A systematic literature review was performed of the impact of a scheduled nap during shift work on EMS personnel or similar shift workers. The primary (critical) outcome of interest was EMS personnel safety. Secondary (important) outcomes were patient safety; personnel performance; acute states of fatigue, alertness, and sleepiness; indicators of sleep duration and/or quality; employee retention/turnover; indicators of long-term health; and cost to the system. Meta-analyses were performed to evaluate the impact of napping on a measure of personnel performance (the psychomotor vigilance test [PVT]) and measures of acute fatigue. Of 4,660 unique records identified, 13 experimental studies were determined relevant and summarized. The effect of napping on reaction time measured at the end of shift was small and non-significant (SMD 0.12, 95% CI -0.13 to 0.36; p = 0.34). Napping during work did not change reaction time from the beginning to the end of the shift (SMD -0.01, 95% CI -25.0 to 0.24; p = 0.96). Naps had a moderate, significant effect on sleepiness measured at the end of shift (SMD 0.40, 95% CI 0.09 to 0.72; p = 0.01). The difference in sleepiness from the start to the end of shift was moderate and statistically significant (SMD 0.41, 95% CI 0.09 to 0.72; p = 0.01). Reviewed literature indicated that scheduled naps at work improved performance and decreased fatigue in shift workers. Further research is required to identify the optimal timing and duration of scheduled naps to maximize the beneficial outcomes.

Influence of rotating shift work on visual reaction time and visual evoked potential.

PubMed

R V, Hemamalini; N, Krishnamurthy; A, Saravanan

2014-10-01

The present day life style is changing the circadian rhythm of the body especially in rotating night shift workers. The impact of this prolongs their reaction time. Night shift also interferes with the circadian variation of pupil size which may affect the visual evoked potential. To compare the visual reaction time, visual evoked potential (VEP) in rotating night shift workers & day workers and also to correlate the changes in visual reaction time with visual evoked potential. Forty healthy male security guards & staff (25 - 35 y) who did rotating night shifts at least for six months & 40 d workers (25 - 35 y) who did not do night shift in last two years were involved in the study. Visual reaction time and the latency & amplitude of VEP were recorded. Kolmogorov- Smirnov test for normalcy showed the latencies & amplitude of VEP to be normally distributed. Student's unpaired t test showed significant difference (p<0.05) in the visual time and in the latencies of VEP between night shift & day workers. There was no significant difference in the amplitude of VEP. Night shift workers who are prone to circadian rhythm alteration will have prolonged visual reaction time & visual evoked potential abnormalities. Implementation of Bright Light Therapy would be beneficial to the night shift worker.

The role of attentional processes in children's prosocial behavior with peers: attention shifting and emotion.

PubMed

Wilson, Beverly J

2003-01-01

This study evaluated the role of attentional shifting in children's prosocial behavior with peers. Participants were 27 aggressive/rejected and 27 nonaggressive/popular kindergarten and first grade boys and girls. Children's ability to shift attention from one affective state to another was assessed during: (a) a computerized task that required shifting attention between different affective events (i.e., the Children's Attentional Shifting Task, CAST) and (b) an analogue entry task with unacquainted peers. Children's latency for sharing with peers was assessed after they experienced failure during the entry task. Aggressive/rejected children had significant difficulty shifting attention from negative to positive affect during the CAST and were slower to share after experiencing entry failure. In general, aggressive/rejected children were less able to regulate their behavior effectively after experiencing social failure. Girls, regardless of status, had less difficulty than boys shifting attention from one affective state to another during the CAST. In addition, children's social status/aggressiveness, their ability to regulate emotional behavior after social failure and to shift attention effectively on the CAST predicted approximately 31% of the variance in their latency to share. These findings suggest that the ability to shift attention between different affective states plays a significant role in children's prosocial behavior with peers.

Associations of long-term shift work with waking salivary cortisol concentration and patterns among police officers.

PubMed

Fekedulegn, Desta; Burchfiel, Cecil M; Violanti, John M; Hartley, Tara A; Charles, Luenda E; Andrew, Michael E; Miller, Diane B

2012-01-01

The objective of this study was to evaluate whether long-term shift work is associated with both the total hormonal secretion after awakening and the pattern of the cortisol levels during the first hour following awakening, among 65 randomly selected police officers who represent a high stress occupation. Dominant shift (Day, Afternoon, or Midnight) was ascertained using daily payroll records of each participant's work activities during the 6-8 yrs prior to saliva sampling. Four salivary samples were collected at 15 min intervals upon first awakening. After accounting for potential confounders, salivary cortisol concentrations averaged across all four time points and total area under the curve differed significantly across shift with midnight shift workers showing suppressed awakening cortisol response relative to the afternoon and day shift. The percent of hours worked on midnight shift was inversely correlated with total awakening cortisol output. In contrast, the pattern of cortisol secretion during the first hour following waking appeared not to be affected as no significant interaction effect was found between time since awakening and shift work. The results show that long-term midnight shift work is associated with decreased absolute mean level and total volume of cortisol released over the waking period.

Associations of Long-term Shift Work with Waking Salivary Cortisol Concentration and Patterns among Police Officers

PubMed Central

FEKEDULEGN, Desta; BURCHFIEL, Cecil M.; VIOLANTI, John M.; HARTLEY, Tara A.; CHARLES, Luenda E.; ANDREW, Michael E.; MILLER, Diane B.

2015-01-01

The objective of this study was to evaluate whether long-term shift work is associated with both the total hormonal secretion after awakening and the pattern of the cortisol levels during the first hour following awakening, among 65 randomly selected police officers who represent a high stress occupation. Dominant shift (Day, Afternoon, or Midnight) was ascertained using daily payroll records of each participant’s work activities during the 6–8 yrs prior to saliva sampling. Four salivary samples were collected at 15 min intervals upon first awakening. After accounting for potential confounders, salivary cortisol concentrations averaged across all four time points and total area under the curve differed significantly across shift with midnight shift workers showing suppressed awakening cortisol response relative to the afternoon and day shift. The percent of hours worked on midnight shift was inversely correlated with total awakening cortisol output. In contrast, the pattern of cortisol secretion during the first hour following waking appeared not to be affected as no significant interaction effect was found between time since awakening and shift work. The results show that long-term midnight shift work is associated with decreased absolute mean level and total volume of cortisol released over the waking period. PMID:23047078

Postprandial metabolic profiles following meals and snacks eaten during simulated night and day shift work.

PubMed

Al-Naimi, S; Hampton, S M; Richard, P; Tzung, C; Morgan, L M

2004-01-01

Shift workers are known to have an increased risk of developing cardiovascular disease (CVD) compared with day workers. An important factor contributing to this increased risk could be the increased incidence of postprandial metabolic risk factors for CVD among shift workers, as a consequence of the maladaptation of endogenous circadian rhythms to abrupt changes in shift times. We have previously shown that both simulated and real shift workers showed relatively impaired glucose and lipid tolerance if a single test meal was consumed between 00:00-02:00 h (night shift) compared with 12:00-14:00 h (day shift). The objective of the present study was to extend these observations to compare the cumulative metabolic effect of consecutive snacks/meals, as might normally be consumed throughout a period of night or day shift work. In a randomized crossover study, eight healthy nonobese men (20-33 yrs, BMI 20-25kg/m2) consumed a combination of two meals and a snack on two occasions following a standardized prestudy meal, simulating night and day shift working (total energy 2500 kcal: 40% fat, 50% carbohydrate, 10% protein). Meals were consumed at 01:00/ 13:00 h and 07:00/19:00h, and the snack at 04:00/16:00 h. Blood was taken after an overnight fast, and for 8 h following the first meal on each occasion, for the measurement of glucose, insulin, triacylglycerol (TAG), and nonesterified fatty acids (NEFA). RM-ANOVA (factors time and shift) showed a significant effect of shift for plasma TAG, with higher levels on simulated night compared to day shift (p < 0.05). There was a trend toward an effect of shift for plasma glucose, with higher plasma glucose at night (p = 0.08), and there was a time-shift interaction for plasma insulin levels (p < 0.01). NEFA levels were unaffected by shift. Inspection of the area under the plasma response curve (AUC) following each meal and snack revealed that the differences in lipid tolerance occurred throughout the study, with greatest differences occurring following the mid-shift snack. In contrast, glucose tolerance was relatively impaired following the first night-time meal, with no differences observed following the second meal. Plasma insulin levels were significantly lower following the first meal (p < 0.05), but significantly higher following the second meal (p < 0.01) on the simulated night shift. These findings confirm our previous observations of raised postprandial TAG and glucose at night, and show that sequential meal ingestion has a more pronounced effect on subsequent lipid than carbohydrate tolerance.

Transcapillary protein flux following blood volume modification in dog.

PubMed

Miki, K; Nose, H; Tanaka, Y; Morimoto, T

1984-01-01

The net fluid and protein movements between intravascular and interstitial space following blood withdrawal and retransfusion of 15% of circulating blood volume were measured in dogs using a continuous monitoring method of circulating blood volume. A significant (p less than 0.01) increase in transvascular fluid shift was observed after the start of blood withdrawal and a new equilibrium state was reached within 15 to 20 min. Associated with the fluid shift, a significant increase in plasma protein of about 1 g was observed. On the other hand, blood retransfusion caused significant (p less than 0.01) increases in the shift of fluid and protein from intravascular space to interstitial space. The magnitudes of the shift of fluid and protein were almost identical in both blood withdrawal and retransfusion. The Kedem-Katchalsky transport equation was applied to the results obtained in the present study in order to analyze the relative role of diffusion and convection and to estimate the reflection coefficient for protein. A significant (p less than 0.01) linear relationship was observed between fluid and protein movement. These results suggest that the convective process is involved in the shift of protein between intravascular and interstitial space observed after blood volume modification.

The Impact of Different Visual Feedbacks in User Training on Motor Imagery Control in BCI.

PubMed

Zapała, Dariusz; Francuz, Piotr; Zapała, Ewelina; Kopiś, Natalia; Wierzgała, Piotr; Augustynowicz, Paweł; Majkowski, Andrzej; Kołodziej, Marcin

2018-03-01

The challenges of research into brain-computer interfaces (BCI) include significant individual differences in learning pace and in the effective operation of BCI devices. The use of neurofeedback training is a popular method of improving the effectiveness BCI operation. The purpose of the present study was to determine to what extent it is possible to improve the effectiveness of operation of sensorimotor rhythm-based brain-computer interfaces (SMR-BCI) by supplementing user training with elements modifying the characteristics of visual feedback. Four experimental groups had training designed to reinforce BCI control by: visual feedback in the form of dummy faces expressing emotions (Group 1); flashing the principal elements of visual feedback (Group 2) and giving both visual feedbacks in one condition (Group 3). The fourth group participated in training with no modifications (Group 4). Training consisted of a series of trials where the subjects directed a ball into a basket located to the right or left side of the screen. In Group 1 a schematic image a face, placed on the controlled object, showed various emotions, depending on the accuracy of control. In Group 2, the cue and targets were flashed with different frequency (4 Hz) than the remaining elements visible on the monitor. Both modifications were also used simultaneously in Group 3. SMR activity during the task was recorded before and after the training. In Group 3 there was a significant improvement in SMR control, compared to subjects in Group 2 and 4 (control). Differences between subjects in Groups 1, 2 and 4 (control) were insignificant. This means that relatively small changes in the training procedure may significantly impact the effectiveness of BCI control. Analysis of behavioural data acquired from all participants at training showed greater effectiveness in directing the object towards the right side of the screen. Subjects with the greatest improvement in SMR control showed a significantly lower difference in the accuracy of rightward and leftward movement than others.

Influence of parainfluenza-1 respiratory tract viral infection on endothelin receptor-effector systems in mouse and rat tracheal smooth muscle.

PubMed Central

Knott, P. G.; Henry, P. J.; McWilliam, A. S.; Rigby, P. J.; Fernandes, L. B.; Goldie, R. G.

1996-01-01

1. In this study we have compared the effects of parainfluenza-1 respiratory tract viral infection on the density and function of ETA and ETB receptors in rat and mouse tracheal airway smooth muscle. 2. The bronchoconstrictor effect of inhaled methacholine was significantly enhanced in virus-infected rats, at both 4 and 12 days post-inoculation. That is, the concentration of methacholine causing an increase in resistance of 100% (PC100 methacholine) was significantly lower in virus-infected animals at both 4 and 12 days post-inoculation (n = 6-8; P < 0.05). 3. Total specific binding of [125I]-endothelin-1 and the relative proportions of ETA and ETB binding sites for [125I]-endothelin-1 were assessed in tracheal airway smooth muscle in parainfluenza-1-infected rats and mice at days 2, 4 and 12 post-inoculation using the ligands BQ-123 (1 microM; ETA receptor-selective) and sarafotoxin S6c (100 nM; ETB receptor-selective). Total specific binding in mice was significantly reduced at day 2 post-inoculation (n = 5; P < 0.05) but not at days 4 and 12 post-inoculation (n = 5). In control mice, the proportions of ETA and ETB binding sites were 53%:47% at day 2 and 43%:57% at day 4 and these were significantly altered by parainfluenza-1 infection such that, the ratios were 81%:19% at day 2 and 89%:11% at day 4 (P < 0.05). By day 12 post-inoculation, the proportion of ETA and ETB binding sites in tracheal smooth muscle from mice infected with parainfluenza-1 was not significantly different from control. In rat tracheal airway smooth muscle, neither total specific binding nor the ETA and ETB binding site ratio (64%:36%) were significantly altered in virus-inoculated rats at days 2, 4 or 12 post-inoculation (n = 5). 4. Parainfluenza-1 infection in mice had no effect on the sensitivity or maximal contractile effect of endothelin-1 in tracheal smooth muscle at days 2, 4 or 12 post-inoculation (n = 4). In contrast, contraction in response to the ETB receptor-selective agonist sarafotoxin S6c was attenuated by 39% at day 2 and by 93% at day 4 post-inoculation (P < 0.05). However, by day 12 post-inoculation, contractions to sarafotoxin S6c were not significantly different between control and virus-infected mice. In parainfluenza-1-infected rats, there were small but significant reductions in the sensitivity to carbachol, endothelin-1 and sarafotoxin S6c whilst the maximal responses to the highest concentrations of these agonists were not significantly altered by virus infection (n = 8). 5. BQ-123 (3 microM) had no significant effect on cumulative concentration-effect curves to endothelin-1 in tracheal preparations from control mice (n = 4) or parainfluenza-1-infected rats (n = 8). In contrast, in tissues taken from virus-infected mice at day 4 post-inoculation, BQ-123 caused a marked 9.6 fold rightward shift in the concentration-effect curve to endothelin-1 (n = 4). 6. In summary, we have demonstrated that parainfluenza-1 infection in mice transiently reduced the density of tracheal airway smooth muscle ETB receptors and this was reflected in reduced responsiveness to the ETB receptor-selective agonist sarafotoxin S6c. In contrast, whilst parainfluenza-1 infection in rats was associated with the pathological features and bronchial hyperresponsiveness common to respiratory tract viral infection, there was no selective down-regulation of ETB receptor expression or functional activity. The reasons for these species differences are not clear, but may relate to differences in the airway inflammatory response to parainfluenza-1 virus. PMID:8886411

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

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

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribedburn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changes inmore » urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

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

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

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

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

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

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changesmore » in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

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

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2008-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Clinical investigation of set-shifting subtypes in anorexia nervosa.

PubMed

Abbate-Daga, Giovanni; Buzzichelli, Sara; Marzola, Enrica; Amianto, Federico; Fassino, Secondo

2014-11-30

While evidence continues to accumulate on the relevance of cognitive inflexibility in anorexia nervosa (AN), its clinical correlates remain unclear. We aimed at examining the relationship between set-shifting and clinical variables (i.e., eating psychopathology, depression, and personality) in AN. Ninety-four individuals affected by AN and 59 healthy controls (HC) were recruited. All participants were assessed using: Eating Disorders Inventory-2 (EDI-2), Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST). The AN group scored worse than HCs on set-shifting. According to their neuropsychological performances, AN patients were split into two groups corresponding to poor (N=30) and intact (N=64) set-shifting subtypes. Interoceptive awareness, impulse regulation, and maturity fears on the EDI-2 and depression on the BDI differed across all groups (HC, intact, and poor set-shifting subtype). Self-directedness on the TCI differed significantly among all groups. Cooperativeness and reward dependence differed instead only between HC and AN poor set-shifting subtype. After controlling for depression, only interoceptive awareness remained significant with reward dependence showing a trend towards statistical significance. These findings suggest that multiple clinical variables may be correlated with set-shifting performances in AN. The factors contributing to impaired cognitive inflexibility could be more complex than heretofore generally considered. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effect of parents' joint work schedules on infants' behavior over the first two years of life: evidence from the ECLSB.

PubMed

Rosenbaum, Emily; Morett, Christopher R

2009-11-01

We test whether infants living with employed, co-resident parents where at least one parent works a non-standard work shift exhibit significantly more behavior problems than children whose parents both work traditional day shifts. We use a sample of infants living with employed, co-resident parents and two waves of data from the Early Childhood Longitudinal Survey, Birth Cohort (ECLSB) to test whether infants' scores on the Infant-Toddler Symptom Checklist (ITSC) at the second wave (average age of 24.3 months) is affected by parents' shift work at the baseline (average age 10.3 months). Infants with at least one parent who works nonstandard hours have significantly more behavior problems than do infants with parents who both work regular day shifts. This relationship is partly accounted for by shift work's negative association with father-child interaction, marital quality, the frequency of shared family dinners, and parental health, including paternal depression. The results also indicate that shift work has larger effects on children's behavior when mothers, rather than fathers, work nonstandard shifts, and when mothers' day shifts regularly oppose fathers' evenings/night shifts. Policy should focus on giving individuals more choice in their work shift as well as more flexibility in when they start and stop working for the day. Given the importance of mediating factors, we should also focus on ameliorating the negative impacts of shift work when they do arise. This includes addressing issues of employee health and stress, and relationship conflict within couples where one or both partners work a non-standard shift.

Fluid losses and hydration status of industrial workers under thermal stress working extended shifts

PubMed Central

Brake, D; Bates, G

2003-01-01

Aims: To assess whether workers under significant thermal stress necessarily dehydrated during their exposure and whether "involuntary dehydration" was inevitable, as supported by ISO 9866 and other authorities. Other objectives were to quantify sweat rates against recommended occupational limits, to develop a dehydration protocol to assist with managing heat exposures, and to understand the role of meal breaks on extended shifts in terms of fluid replacement. Methods: A field investigation to examine the fluid consumption, sweat rates, and changes in the hydration state of industrial workers on extended (10, 12, and 12.5 hour) shifts under significant levels of thermal stress (wet bulb globe temperature (WBGT) >28°C) was conducted on 39 male underground miners. Urinary specific gravity was measured before, during, and at the completion of the working shift. Environmental conditions were measured hourly during the shift. Fluid replacement was measured during the working periods and during the meal breaks. Results: Average environmental conditions were severe (WBGT 30.9°C (SD 2.0°C), range 25.7–35.2°C). Fluid intake averaged 0.8 l/h during exposure (SD 0.3 l/h, range 0.3–1.5 l/h). Average urinary specific gravity at start, mid, and end of shift was 1.0251, 1.0248, and 1.0254 respectively; the differences between start and mid shift, mid and end shift, and start and end shift were not significant. However, a majority of workers were coming to work in a moderately hypohydrated state (average urinary specific gravity 1.024 (SD 0.0059)). A combined dehydration and heat illness protocol was developed. Urinary specific gravity limits of 1.022 for start of shift and 1.030 for end of shift were selected; workers exceeding these values were not allowed into the workplace (if the start of shift limit was exceeded) or were retested prior to their next working shift (if the end of shift limit was exceeded). A target of 1.015 as a euhydrated state for start of shift was adopted for workforce education. Conclusions: This study found that "involuntary dehydration" did not occur in well informed workers, which has implications for heat stress standards that do not make provision for full fluid replacement during heat exposure. Fluid replacement during meal breaks was not significantly increased above fluid replacement rates during work time, with implications for the duration and spacing of meal breaks on long shifts. Testing of urinary specific gravity was found to be a good indication of hydration status and a practical method of improving workforce awareness and understanding of this important risk factor. Approximately 10 000 dehydration tests have been conducted under the dehydration protocol in a workforce of 2000 persons exposed to thermal stress and has proved practical and reliable. PMID:12554834

Nutrition and health in hotel staff on different shift patterns.

PubMed

Seibt, R; Süße, T; Spitzer, S; Hunger, B; Rudolf, M

2015-08-01

Limited research is available that examines the nutritional behaviour and health of hotel staff working alternating and regular shifts. To analyse the nutritional behaviour and health of employees working in alternating and regular shifts. The study used an ex post facto cross-sectional analysis to compare the nutritional behaviour and health parameters of workers with alternating shifts and regular shift workers. Nutritional behaviour was assessed with the Food Frequency Questionnaire. Body dimensions (body mass index, waist hip ratio, fat mass and active cell mass), metabolic values (glucose, triglyceride, total cholesterol and low- and high-density lipoprotein), diseases and health complaints were included as health parameters. Participants worked in alternating (n = 53) and regular shifts (n = 97). The average age of subjects was 35 ± 10 years. There was no significant difference in nutritional behaviour, most surveyed body dimensions or metabolic values between the two groups. However, alternating shift workers had significantly lower fat mass and higher active cell mass but nevertheless reported more pronounced health complaints. Sex and age were also confirmed as influencing the surveyed parameters. Shift-dependent nutritional problems were not conspicuously apparent in this sample of hotel industry workers. Health parameters did not show significantly negative attributes for alternating shift workers. Conceivably, both groups could have the same level of knowledge on the health effects of nutrition and comparable opportunities to apply this. Further studies on nutritional and health behaviour in the hotel industry are necessary in order to create validated screening programmes. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Self-Reported Recovery from 2-Week 12-Hour Shift Work Schedules: A 14-Day Follow-Up

PubMed Central

Merkus, Suzanne L.; Holte, Kari Anne; Huysmans, Maaike A.; van de Ven, Peter M.; van Mechelen, Willem; van der Beek, Allard J.

2015-01-01

Background Recovery from fatigue is important in maintaining night workers' health. This study compared the course of self-reported recovery after 2-week 12-hour schedules consisting of either night shifts or swing shifts (i.e., 7 night shifts followed by 7 day shifts) to such schedules consisting of only day work. Methods Sixty-one male offshore employees—20 night workers, 16 swing shift workers, and 25 day workers—rated six questions on fatigue (sleep quality, feeling rested, physical and mental fatigue, and energy levels; scale 1–11) for 14 days after an offshore tour. After the two night-work schedules, differences on the 1st day (main effects) and differences during the follow-up (interaction effects) were compared to day work with generalized estimating equations analysis. Results After adjustment for confounders, significant main effects were found for sleep quality for night workers (1.41, 95% confidence interval 1.05–1.89) and swing shift workers (1.42, 95% confidence interval 1.03–1.94) when compared to day workers; their interaction terms were not statistically significant. For the remaining fatigue outcomes, no statistically significant main or interaction effects were found. Conclusion After 2-week 12-hour night and swing shifts, only the course for sleep quality differed from that of day work. Sleep quality was poorer for night and swing shift workers on the 1st day off and remained poorer for the 14-day follow-up. This showed that while working at night had no effect on feeling rested, tiredness, and energy levels, it had a relatively long-lasting effect on sleep quality. PMID:26929834

The Differential Effects of Regular Shift Work and Obstructive Sleep Apnea on Sleepiness, Mood and Neurocognitive Function.

PubMed

Cori, Jennifer M; Jackson, Melinda L; Barnes, Maree; Westlake, Justine; Emerson, Paul; Lee, Jacen; Galante, Rosa; Hayley, Amie; Wilsmore, Nicholas; Kennedy, Gerard A; Howard, Mark

2018-06-15

To assess whether poor sleep quality experienced by regular shift workers and individuals with obstructive sleep apnea (OSA) affects neurobehavioral function similarly, or whether the different etiologies have distinct patterns of impairment. Thirty-seven shift workers (> 24 hours after their last shift), 36 untreated patients with OSA, and 39 healthy controls underwent assessment of sleepiness (Epworth Sleepiness Scale [ESS]), mood (Beck Depression Index, State Trait Anxiety Inventory [STAI], Profile of Mood States), vigilance (Psychomotor Vigilance Task [PVT], Oxford Sleep Resistance Test [OSLER], driving simulation), neurocognitive function (Logical Memory, Trails Making Task, Digit Span Task, Victoria Stroop Test) and polysomnography. Sleepiness (ESS score; median, interquartile range) did not differ between the OSA (10.5, 6.3-14) and shift work (7, 5-11.5) groups, but both had significantly elevated scores relative to the control group (5, 3-6). State anxiety (STAI-S) was the only mood variable that differed significantly between the OSA (35, 29-43) and shift work (30, 24-33.5) groups, however both demonstrated several mood deficits relative to the control group. The shift work and control groups performed similarly on neurobehavioral tasks (simulated driving, PVT, OSLER and neurocognitive tests), whereas the OSA group performed worse. On the PVT, lapses were significantly greater for the OSA group (3, 2-6) than both the shift work (2, 0-3.5) and control (1, 0-4) groups. Shift workers and patients with OSA had similar sleepiness and mood deficits relative to healthy individuals. However, only the patients with OSA showed deficits on vigilance and neurocognitive function relative to healthy individuals. These findings suggest that distinct causes of sleep disturbance likely result in different patterns of neurobehavioral dysfunction. © 2018 American Academy of Sleep Medicine.

Roles of safety climate and shift work on perceived injury risk: a multi-level analysis.

PubMed

Huang, Yueng-Hsiang; Chen, Jiu-Chiuan; DeArmond, Sarah; Cigularov, Konstantin; Chen, Peter Y

2007-11-01

This study evaluated the relationship between employees' work shift (i.e., day shift versus night shift) and perceptions of injury risk, and how the relationship is affected by company level safety climate and injury frequency. The results showed that night shift workers perceived a higher level of injury risk compared to day shift workers. Both company level safety climate and injury frequency played critical roles in predicting individual perceived work injury risk. Perception of injury risk of night shift workers was significantly lower when they perceived high-level rather than low-level safety climate. However, this pattern was not noticeable for day shift workers. These findings highlighted the importance of considering company level factors when attempting to understand the differences between day shift and night shift work on an individual's perception of injury risk.

Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the guinea-pig ileum and proximal colon.

PubMed Central

Maggi, C. A.; Patacchini, R.; Meini, S.; Quartara, L.; Sisto, A.; Potier, E.; Giuliani, S.; Giachetti, A.

1994-01-01

1. The aim of this study was the pharmacological characterization of tachykinin NK1 and NK2 receptors mediating contraction in the circular muscle of the guinea-pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA) and of the synthetic agonists [Sar9]SP sulphone, [Glp6,Pro9]SP(6-11) (septide) and [beta Ala8]NKA(4-10) was investigated. The affinities of various peptide and nonpeptide antagonists for the NK1 and NK2 receptor was estimated by use of receptor selective agonists. 2. The natural agonists, SP and NKA, produced concentration-dependent contraction in both preparations. EC50 values were 100 pM and 5 nM for SP, 1.2 nM and 19 nM for NKA in the ileum and colon, respectively. The action of SP and NKA was not significantly modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). 3. Synthetic NK1 and NK2 receptor agonists produced concentration-dependent contraction of the circular muscle of the ileum and proximal colon. EC50 values were 83 pM, 36 pM and 10 nM in the ileum, 8 nM, 0.7 nM and 12 nM in the colon for [Sar9]SP sulphone, septide and [beta Ala8]NKA-(4-10), respectively. The pseudopeptide derivative of NKA(4-10), MDL 28,564 behaved as a full or near-to-full agonist in both preparations, its EC50s being 474 nM and 55 nM in the ileum and colon, respectively. 4. Nifedipine (1 microM) abolished the response to septide and [Sar9]SP sulphone in the ileum and produced a rightward shift and large depression of the response in the colon. The response to [beta Ala8]NKA(4-10) was abolished in the ileum and largely unaffected in the colon. 5. The NK1 receptor antagonists, (+/-)-CP 96,34, FK 888 and GR 82,334 competitively antagonized the response to septide and [Sar9]SP sulphone in both preparations without affecting that to [beta Ala8]NKA(4-10). In general, the NK1 receptor antagonists were significantly more potent toward septide than [Sar9]SP sulphone in both preparations. 6. The NK2 receptor antagonists, GR 94,800 and SR 48,968 selectively antagonized the response to [beta Ala8]NKA(4-10) without affecting that to [Sar9]SP sulphone or septide in the ileum and colon. SR 48,968 produced noncompetitive antagonism of the response to the NK2 receptor agonist in the ileum and competitive antagonism in the colon. 7. MEN 10,376 and the cyclic pseudopeptide MEN 10,573 antagonized in a competitive manner the response to [beta Ala8]NKA(4-10) in the ileum and colon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7518302

A prospective study of psychomotor performance of driving among two kinds of shift work in Iran

PubMed Central

Saadat, Soheil; Karbakhsh, Mojgan; Saremi, Mahnaz; Alimohammadi, Iraj; Ashayeri, Hassan; Fayaz, Mahsa; Rostami, Reza

2018-01-01

Background and aim Driving after a night shift imposes a risk on health care professionals and other road users. The aim of this study was to measure psychomotor performance of driving of night shift nurses compared to day-shift nurses. Methods Forty-seven volunteer female nurses working at Sina hospital in Tehran, Iran, with a call in all departments of hospital, participated in this study (23 night shift and 24 day shift nurses) in 2016. The tests included RT for simple reaction time, ATAVT for perceptual speed, LVT for visual orientation and ZBA for time anticipation. Data collection tools were individual characteristics, 11-item circadian type inventory (CTI), Stanford sleepiness scale (SSS), and Swedish occupational fatigue inventory (SOFI-20) questionnaires. Psychomotor driving performance was assessed using validated computerized traffic psychological battery of Vienna Test System (VTS), before and after the shifts. Data analysis was performed using paired-samples t-test and Linear Regression. Results The mean age of day and night-shift nurses were 31.4±5.6 and 28.7±3.9 years respectively, no significant difference between two groups. Thirty percent of night shift and 16.7% of day shift nurses reported traffic accidents in the past year. The results revealed that, scores based on viewing times in visual orientation test (p=0.005), and median reaction time score in choice reaction time and reactive stress tolerance test (p=0.045), had a significant association with a 12-hour night shift with a 3-hour nap. Conclusions Twelve-hour night shift work impairs choice reaction time and visual orientation in nurses, even though they take a 3- hour nap during the shift. These skills are required for safe driving. PMID:29629067

Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine.

PubMed Central

Souness, J. E.; Brazdil, R.; Diocee, B. K.; Jordan, R.

1989-01-01

1. The mechanism by which M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine (MIMAX), which have been described as selective cyclic GMP phosphodiesterase (PDE) inhibitors, relax rat aorta was investigated. 2. Three cyclic nucleotide PDEs were identified in the soluble fraction of rat aorta; a Ca2+-insensitive form exhibiting substrate selectivity for cyclic GMP (cGMP PDE), a Ca2+/calmodulin-stimulated form which also preferentially hydrolyzed cyclic GMP (Ca2+ PDE), and a form demonstrating substrate selectivity for cyclic AMP (cAMP PDE). 3. M&B 22,948 and MIMAX inhibited cGMP PDE (Ki = 0.16 microM and 0.43 microM, respectively) and Ca2+ PDE (Ki = 9.9 microM and 0.55 microM, respectively), but exhibited weak activity against cAMP PDE (Ki = 249 microM and 42 microM, respectively). MY-5445 selectivity inhibited cGMP PDE (Ki = 1.3 microM) and vinpocetine selectively inhibited Ca2+ PDE (Ki = 14 microM). 4. M&B 22,948 and MIMAX induced dose-dependent increases in the accumulation of cyclic GMP, but not cyclic AMP, in rat aorta pieces. These effects were greatly reduced by endothelial denudation and by methylene blue (5 microM) which blocks the actions of endothelium-derived relaxant factor. MY-5445 and vinpocetine had no effect on rat aorta cyclic GMP or cyclic AMP accumulation. 5. All four compounds caused dose-related relaxation of 5-hydroxytryptamine (10 microM) contracted, endothelium-intact rat aorta, the effects of M&B 22,948 and MIMAX being greatly reduced by methylene blue (5 microM). Methylene blue also caused 10 fold and 100 fold rightward shifts in the dose-response curves of MY-5445 and vinpocetine, respectively. 6. The results are consistent with the smooth muscle relaxant actions of M&B 22,948 and MIMAX, but not vinpocetine and MY-5445, being mediated through a mechanism involving inhibition of cyclic GMP hydrolysis. PMID:2480168

Progression from homologous to heterologous desensitization of contraction in gastric smooth muscle cells.

PubMed

Severi, C; Carnicelli, V; di Giulio, A; Romano, G; Bozzi, A; Oratore, A; Strom, R; delle Fave, G

1999-02-01

Acute desensitization of contraction and its relative mechanisms have been studied in smooth muscle cells isolated from guinea pig stomach. Desensitization was induced by pre-exposure of the cells to one of the excitatory neuropeptides linked to the phospholipase C intracellular cascade, i.e., cholecystokinin (CCK), gastrin-releasing peptide, and Substance P. Desensitization was homologous after a 30-s pre-exposure and heterologous if pre-exposure lasted for 5 min or longer. Homologous desensitization was studied in a more detailed way after pre-exposure to CCK. Preincubation with increasing concentrations of CCK (10 pM-1 microM) induced a progressive rightward shift of the dose-response curves associated with both a decrease in potency (ED50 4.5 pM-2.2 nM) and a maximum response that were not related to a modification of response kinetics. After brief pre-exposure to 1 nM CCK (Dmax), an inhibition of contraction was observed in response to an identical dose of CCK (45.1 +/- 8.6%), the decreased response being associated with an inhibition of inositol phosphates and [Ca++]i mobilization. Both inositol trisphosphate (InsP3)-induced contraction and [Ca++]i mobilization were inhibited to a lesser extent than CCK-induced responses. Any longer pre-exposure of cells to one of the above-mentioned neuropeptides caused heterologous desensitization, with an observed inhibition of contraction in response to all tested agonists (CCK, 60.3 +/- 5.9%; gastrin-releasing peptide: 56.7 +/- 3. 5%; Substance P, 60.6 +/- 6.5%). A similar decrease was observed in InsP3-induced contractions resulting in a desensitization of the InsP3 response as well. Full recovery of contractile responses appeared within 30 min from the end of preincubation, thus indicating that degradation of membrane receptors did not occur. Although pre-exposure of the cells to protein kinase C inhibitor GF109203X did not modify CCK-induced homologous desensitization, it blocked CCK-induced heterologous desensitization. This study demonstrates that excitatory phospholipase C-coupled enteric neuropeptides induce a time-dependent homologous as well as heterologous desensitization of smooth muscle contraction occurring at receptor and postreceptor levels.

Analyses of frameshifting at UUU-pyrimidine sites.

PubMed

Schwartz, R; Curran, J F

1997-05-15

Others have recently shown that the UUU phenylalanine codon is highly frameshift-prone in the 3'(rightward) direction at pyrimidine 3'contexts. Here, several approaches are used to analyze frameshifting at such sites. The four permutations of the UUU/C (phenylalanine) and CGG/U (arginine) codon pairs were examined because they vary greatly in their expected frameshifting tendencies. Furthermore, these synonymous sites allow direct tests of the idea that codon usage can control frameshifting. Frameshifting was measured for these dicodons embedded within each of two broader contexts: the Escherichia coli prfB (RF2 gene) programmed frameshift site and a 'normal' message site. The principal difference between these contexts is that the programmed frameshift contains a purine-rich sequence upstream of the slippery site that can base pair with the 3'end of 16 S rRNA (the anti-Shine-Dalgarno) to enhance frameshifting. In both contexts frameshift frequencies are highest if the slippery tRNAPhe is capable of stable base pairing in the shifted reading frame. This requirement is less stringent in the RF2 context, as if the Shine-Dalgarno interaction can help stabilize a quasi-stable rephased tRNA:message complex. It was previously shown that frameshifting in RF2 occurs more frequently if the codon 3'to the slippery site is read by a rare tRNA. Consistent with that earlier work, in the RF2 context frameshifting occurs substantially more frequently if the arginine codon is CGG, which is read by a rare tRNA. In contrast, in the 'normal' context frameshifting is only slightly greater at CGG than at CGU. It is suggested that the Shine-Dalgarno-like interaction elevates frameshifting specifically during the pause prior to translation of the second codon, which makes frameshifting exquisitely sensitive to the rate of translation of that codon. In both contexts frameshifting increases in a mutant strain that fails to modify tRNA base A37, which is 3'of the anticodon. Thus, those base modifications may limit frameshifting at UUU codons. Finally, statistical analyses show that UUU Ynn dicodons are extremely rare in E.coli genes that have highly biased codon usage.

Analyses of frameshifting at UUU-pyrimidine sites.

PubMed Central

Schwartz, R; Curran, J F

1997-01-01

Others have recently shown that the UUU phenylalanine codon is highly frameshift-prone in the 3'(rightward) direction at pyrimidine 3'contexts. Here, several approaches are used to analyze frameshifting at such sites. The four permutations of the UUU/C (phenylalanine) and CGG/U (arginine) codon pairs were examined because they vary greatly in their expected frameshifting tendencies. Furthermore, these synonymous sites allow direct tests of the idea that codon usage can control frameshifting. Frameshifting was measured for these dicodons embedded within each of two broader contexts: the Escherichia coli prfB (RF2 gene) programmed frameshift site and a 'normal' message site. The principal difference between these contexts is that the programmed frameshift contains a purine-rich sequence upstream of the slippery site that can base pair with the 3'end of 16 S rRNA (the anti-Shine-Dalgarno) to enhance frameshifting. In both contexts frameshift frequencies are highest if the slippery tRNAPhe is capable of stable base pairing in the shifted reading frame. This requirement is less stringent in the RF2 context, as if the Shine-Dalgarno interaction can help stabilize a quasi-stable rephased tRNA:message complex. It was previously shown that frameshifting in RF2 occurs more frequently if the codon 3'to the slippery site is read by a rare tRNA. Consistent with that earlier work, in the RF2 context frameshifting occurs substantially more frequently if the arginine codon is CGG, which is read by a rare tRNA. In contrast, in the 'normal' context frameshifting is only slightly greater at CGG than at CGU. It is suggested that the Shine-Dalgarno-like interaction elevates frameshifting specifically during the pause prior to translation of the second codon, which makes frameshifting exquisitely sensitive to the rate of translation of that codon. In both contexts frameshifting increases in a mutant strain that fails to modify tRNA base A37, which is 3'of the anticodon. Thus, those base modifications may limit frameshifting at UUU codons. Finally, statistical analyses show that UUU Ynn dicodons are extremely rare in E.coli genes that have highly biased codon usage. PMID:9115369

Hydration amongst nurses and doctors on-call (the HANDS on prospective cohort study).

PubMed

El-Sharkawy, Ahmed M; Bragg, Damian; Watson, Phillip; Neal, Keith; Sahota, Opinder; Maughan, Ronald J; Lobo, Dileep N

2016-08-01

Dehydration of as little 2% of total body weight may impair physical and cognitive performance. The aim of this study was to investigate the prevalence of dehydration at the start and end of shifts in nurses and doctors on-call. The secondary aims were to assess the relation between hydration status and cognitive function. This prospective cohort study was conducted on nurses and doctors working on medical and surgical admissions wards at a university teaching hospital. Participants arrived on the ward approximately 20 min before their shift and were asked to provide a urine sample. Height and weight were then measured. A 10 mL blood sample was analysed for full blood count, serum urea and electrolytes, and blood glucose. Cognitive function was assessed using a series of computer-based tests including the Stroop Colour Naming Interference Test and Sternberg Memory Paradigm. Participants then worked normally but were asked to keep a fluid diary for the duration of their shift and fluid balance was estimated. Tests were repeated at the end of the shift. Dehydration was defined as urine osmolality >800 mOsmol/kg and oliguria was defined as urine output <0.5 ml/kg/hour. We recruited 92 nurses and doctors, of whom 88 completed the study, amounting to 130 shifts. 52% participated for one shift, and 48% for two shifts. Thirty-six percent of participants were dehydrated at the start of the shift and 45% were dehydrated at the end of their shift. Mean (SD) urinary osmolality was significantly greater at the end of the shift when compared with the start [720 (282) vs. 622 (297) mOsm/kg, P = 0.031). Moreover, 41% were oliguric at the end of the shift. Single number and five-letter Sternberg short-term memory tests were significantly impaired in dehydrated participants (P < 0.05). This study highlights that a significant proportion of nurses and doctors were dehydrated at the start and end of medical and surgical shifts. Dehydration was associated with some impairment of cognitive function. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Effects of pharmacological agents on subcortical resistance shifts

NASA Technical Reports Server (NTRS)

Klivington, K. A.

1975-01-01

Microliter quantities of tetrodotoxin, tetraethylammonium chloride, and picrotoxin injected into the inferior colliculus and superior olive of unanesthetized cats differentially affect the amplitude and waveform of click-evoked potentials and evoked resistance shifts. Tetrodotoxin simultaneously reduces the negative phase of the evoked potential and eliminates the evoked resistance shift. Tetraethylammonium enhances the negative evoked potential component, presumably of postsynaptic origin, without significantly altering evoked resistance shift amplitude. Picrotoxin also enhances the negative evoked potential wave but increases evoked resistance shift amplitude. These findings implicate events associated with postsynaptic membrane depolarization in the production of the evoked resistance shift.

Overnight shift work: factors contributing to diagnostic discrepancies.

PubMed

Hanna, Tarek N; Loehfelm, Thomas; Khosa, Faisal; Rohatgi, Saurabh; Johnson, Jamlik-Omari

2016-02-01

The aims of the study are to identify factors contributing to preliminary interpretive discrepancies on overnight radiology resident shifts and apply this data in the context of known literature to draw parallels to attending overnight shift work schedules. Residents in one university-based training program provided preliminary interpretations of 18,488 overnight (11 pm–8 am) studies at a level 1 trauma center between July 1, 2013 and December 31, 2014. As part of their normal workflow and feedback, attendings scored the reports as major discrepancy, minor discrepancy, agree, and agree--good job. We retrospectively obtained the preliminary interpretation scores for each study. Total relative value units (RVUs) per shift were calculated as an indicator of overnight workload. The dataset was supplemented with information on trainee level, number of consecutive nights on night float, hour, modality, and per-shift RVU. The data were analyzed with proportional logistic regression and Fisher's exact test. There were 233 major discrepancies (1.26 %). Trainee level (senior vs. junior residents; 1.08 vs. 1.38 %; p < 0.05) and modality were significantly associated with performance. Increased workload affected more junior residents' performance, with R3 residents performing significantly worse on busier nights. Hour of the night was not significantly associated with performance, but there was a trend toward best performance at 2 am, with subsequent decreased accuracy throughout the remaining shift hours. Improved performance occurred after the first six night float shifts, presumably as residents acclimated to a night schedule. As overnight shift work schedules increase in popularity for residents and attendings, focused attention to factors impacting interpretative accuracy is warranted.

Localizing and tracking electrodes using stereovision in epilepsy cases

NASA Astrophysics Data System (ADS)

Fan, Xiaoyao; Ji, Songbai; Roberts, David W.; Paulsen, Keith D.

2015-03-01

In epilepsy cases, subdural electrodes are often implanted to acquire intracranial EEG (iEEG) for seizure localization and resection planning. However, the electrodes may shift significantly between implantation and resection, during the time that the patient is monitored for iEEG recording. As a result, the accuracy of surgical planning based on electrode locations at the time of resection can be compromised. Previous studies have only quantified the electrode shift with respect to the skull, but not with respect to the cortical surface, because tracking cortical shift between surgeries is challenging. In this study, we use an intraoperative stereovision (iSV) system to visualize and localize the cortical surface as well as electrodes, record three-dimensional (3D) locations of the electrodes in MR space at the time of implantation and resection, respectively, and quantify the raw displacements, i.e., with respect to the skull. Furthermore, we track the cortical surface and quantify the shift between surgeries using an optical flow (OF) based motion-tracking algorithm. Finally, we compute the electrode shift with respect to the cortical surface by subtracting the cortical shift from raw measured displacements. We illustrate the method using one patient example. In this particular patient case, the results show that the electrodes not only shifted significantly with respect to the skull (8.79 +/- 3.00 mm in the lateral direction, ranging from 2.88 mm to 12.87 mm), but also with respect to the cortical surface (7.20 +/- 3.58 mm), whereas the cortical surface did not shift significantly in the lateral direction between surgeries (2.23 +/- 0.76 mm).

Shift work and hypertension: Prevalence and analysis of disease pathways in a German car manufacturing company.

PubMed

Ohlander, Johan; Keskin, Mekail-Cem; Stork, Joachim; Radon, Katja

2015-05-01

Hypertension and cardiovascular disease (CVD) may share a similar pathophysiology. Despite shift workers' CVD excess risk, studies on shift work and hypertension are inconclusive. Blood pressure and shift status for 25,343 autoworkers were obtained from medical check-ups and company registers. Cross-sectional associations modeling the total effect from shift work (day shifts, shift work without nights, rotating shift work with nights, and night shifts) on hypertension were assessed. By sequential adjustments, the influence of behavioral, psychosocial, and physiological factors on the total effect was examined, with subsequent mediation and moderation analyses. Adjusted for confounders, shift work without nights (vs. day shifts) was significantly associated with hypertension (OR 1.15, 95%CI 1.02-1.30). The total effect was mediated by BMI, physical inactivity, and sleep disorders. No moderation of the total effect by behaviors was found. The association between shift work and hypertension seems mainly attributable to behavioral mechanisms. © 2015 Wiley Periodicals, Inc.

Restless Legs Syndrome/Willis-Ekbom Disease Is Prevalent in Working Nurses, but Seems Not to Be Associated with Shift Work Schedules.

PubMed

Waage, Siri; Pallesen, Ståle; Moen, Bente Elisabeth; Bjorvatn, Bjørn

2018-01-01

Insomnia and excessive sleepiness are among the most commonly reported sleep problems related to shift work. Sleep-related movement disorders have, however, received far less attention in relation to such work schedules. The objective of this study was to investigate the association between different shift work schedules and the prevalence of Restless legs syndrome/Willis-Ekbom disease (RLS/WED) in a large sample of Norwegian nurses. Our hypothesis was that shift working nurses would report higher prevalence of RLS/WED compared to day workers. A total of 1,788 nurses with different work schedules (day work, two-shift rotation, night work, three shift rotation) participated in a cohort study, started in 2008/2009. Four questions about RLS/WED based on the diagnostic criteria were included in wave 4 (2012). RLS/WED prevalence rates across different shift schedules were explored by the Pearson chi-square test. Logistic regression analysis was used to assess the association between RLS/WED and work schedules and shift work disorder (SWD) with adjustment for sex, age, marital status, smoking, and caffeine use. In total, 90.0% of the nurses were females, mean age 36.5 years (SD = 8.6, range 25-67). The overall prevalence of RLS/WED was 26.8%. We found no significant differences between the prevalence of RLS/WED across the different shift schedules, ranging from 23.3% (day work) to 29.4% (night work). There was a significant difference ( p  < 0.001) in the prevalence of RLS/WED between nurses having SWD (33.5%) compared to nurses not having SWD (23.8%). SWD remained significantly associated with RLS/WED in the adjusted logistic regression analysis (1.56, CI: 1.24-1.97). This study did not support the hypothesis. RLS/WED was associated with SWD, which might indicate that nurses vulnerable to shift work also are sensitive to other complaints related to a misalignment of the biological clock.

Response shift in quality of life assessment among cancer patients: A study from Iran

PubMed Central

Hosseini, Bayan; Nedjat, Saharnaz; Zendehdel, Kazem; Majdzadeh, Reza; Nourmohammadi, Azam; Montazer, Ali

2017-01-01

Background: During the course of disease, particularly of chronic diseases, changes in internal standards cause certain changes in the estimation of quality of life (QOL). These changes indicate the phenomenon of ‘response shift’. The present study aimed at assessing response shift in different scales of QOL in Iranian cancer patients. Methods: To assess response shift through the ‘then test’ approach, we asked 211 cancer patients to complete the EORTC QLQ-C30 questionnaire at pretest (at the beginning of the study), posttest (3 months later), and then test (administered immediately after the posttest). Paired t test and Cohen’s effect size were used for comparison. Results: Response shift was significant in all 4 scales under study, i.e. fatigue, pain, emotional functioning, and general QOL (p<0.001). Fatigue, pain, and global QOL have deteriorated significantly with then test approach and emotional function was significantly improved. Conclusion: We observed a response shift in Iranian cancer patients in our study. Thus, in light of the multifactorial nature of QOL and the effect of the response shift bias on different aspects of QOL changes, it is of utmost importance to keep this bias in mind when interpreting the results and managing cancer patients’ treatment regimens. PMID:29951421

Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.

PubMed

Ko, Andrew L; Magown, Philippe; Ozpinar, Alp; Hamzaoglu, Vural; Burchiel, Kim J

2018-05-30

Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement. © 2018 S. Karger AG, Basel.

Rotating night shift work, sleep quality, selected lifestyle factors and prolactin concentration in nurses and midwives.

PubMed

Bukowska, Agnieszka; Sobala, Wojciech; Peplonska, Beata

2015-04-01

The pattern of secretion of many hormones, including prolactin, is dependent on the circadian rhythm. Night shift work involves exposure to artificial light at night and sleep deficiency, which in turn can affect prolactin synthesis. The aim of this study was to evaluate a possible association between night shift work characteristics, sleep quality, lifestyle factors and prolactin concentration, using data from a cross-sectional study of nurses and midwives. A cross-sectional study was conducted among 327 nurses and midwives currently working on rotating night shifts, and 330 nurses and midwives working during the day (aged 40-60 years) (388 premenopausal and 269 postmenopausal). Information about night shift work characteristics, lifestyle, reproductive factors, sleep pattern and other covariates was collected through a face-to-face interview, and from a one-week work and sleep diary completed by the subjects. Weight and height were measured. Prolactin concentration was measured in the morning blood sample using the electrochemiluminesence immunoassay method. Associations were analyzed using linear regression models adjusted for important confounders. Analyses were carried out separately in pre- and postmenopausal women. None of the night shift work or sleep characteristics was significantly associated with prolactin concentration. Prolactin concentration was significantly (p < 0.05) inversely associated with smoking and time of blood sample collection. These results were consistent among both pre- and postmenopausal women. Nulliparity was significantly positively associated with prolactin among premenopausal women, but inversely among postmenopausal. Age was related to prolactin among postmenopausal women only. Our study indicates that rotating night shift work is not associated with prolactin concentration. Smoking, parity, time of blood collection and age among postmenopausal women were significant determinants of prolactin.

Shift Work and Shift Work Sleep Disorder: Clinical and Organizational Perspectives.

PubMed

Wickwire, Emerson M; Geiger-Brown, Jeanne; Scharf, Steven M; Drake, Christopher L

2017-05-01

Throughout the industrialized world, nearly one in five employees works some form of nontraditional shift. Such shift work is associated with numerous negative health consequences, ranging from cognitive complaints to cancer, as well as diminished quality of life. Furthermore, a substantial percentage of shift workers develop shift work disorder, a circadian rhythm sleep disorder characterized by excessive sleepiness, insomnia, or both as a result of shift work. In addition to adverse health consequences and diminished quality of life at the individual level, shift work disorder incurs significant costs to employers through diminished workplace performance and increased accidents and errors. Nonetheless, shift work will remain a vital component of the modern economy. This article reviews seminal and recent literature regarding shift work, with an eye toward real-world application in clinical and organizational settings. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Associations between shift schedule characteristics with sleep, need for recovery, health and performance measures for regular (semi-)continuous 3-shift systems.

PubMed

van de Ven, Hardy A; Brouwer, Sandra; Koolhaas, Wendy; Goudswaard, Anneke; de Looze, Michiel P; Kecklund, Göran; Almansa, Josue; Bültmann, Ute; van der Klink, Jac J L

2016-09-01

In this cross-sectional study associations were examined between eight shift schedule characteristics with shift-specific sleep complaints and need for recovery and generic health and performance measures. It was hypothesized that shift schedule characteristics meeting ergonomic recommendations are associated with better sleep, need for recovery, health and performance. Questionnaire data were collected from 491 shift workers of 18 companies with 9 regular (semi)-continuous shift schedules. The shift schedule characteristics were analyzed separately and combined using multilevel linear regression models. The hypothesis was largely not confirmed. Relatively few associations were found, of which the majority was in the direction as expected. In particular early starts of morning shifts and many consecutive shifts seem to be avoided. The healthy worker effect, limited variation between included schedules and the cross-sectional design might explain the paucity of significant results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overnight fluid shifts in subjects with and without obstructive sleep apnea

PubMed Central

Ding, Ning; Lin, Wei; Zhang, Xi-Long; Ding, Wen-Xiao; Gu, Bing; Ni, Bu-Qing; Zhang, Wei; Zhang, Shi-Jiang

2014-01-01

Objective To investigate the characteristics of baseline body fluid content and overnight fluid shifts between non-obstructive sleep apnea (non-OSA) and obstructive sleep apnea (OSA) subjects. Methods A case-controlled study was performed between February 2013 and January 2014, with 36 (18 OSA and 18 non-OSA) outpatients enrolled in this study. Polysomnographic parameters and results of body fluid were compared between the two groups. Results There were no differences in age, weight, and body mass index (BMI) between groups. Compared with the non-OSA group, OSA group had significantly higher neck circumference (NC) and fluid volume shift in the legs. OSA patients had higher left and right leg fluid indices than non-OSA subjects. There were significant correlations between apnoea-hypopnoea index and baseline fluid indices in both legs as well as the reduction in overnight change in both legs fluid volume. The increase in NC was also significantly correlated with the reduction in overnight change in both legs fluid volume, but not with the change in head and neck fluid volume. There were significant correlations between change in NC and increased fluid shifts in head and neck volume. Conclusions OSA patients had a higher baseline fluid content in both legs as compared with non-OSA subjects, which may be the basic factor with regards to fluid shifts in OSA patients. The increase in head and neck fluid shift volume did not directly correlate with the severity of OSA. PMID:25589967

Variations of cortisol, fatigue and sleep disturbances in sound engineers: effect of job task and fast backward-rotating shifts.

PubMed

Vangelova, Katia K

2008-01-01

The aim was to study the effect of job task and fast backward-rotating shifts on the time-of-day variations of cortisol, fatigue, and sleep disturbances in broadcasting sound engineers. The concentration of saliva cortisol and ratings of stress, sleepiness, and fatigue were followed at 3-hour intervals during the fast backward-rotating shifts in 26 sound engineers: 14 subjects from control rooms, aged 45.1 +/- 7.3 years, and 12 subjects working in direct transmissions, aged 51.7 +/- 6.0 years. Saliva cortisol was assessed using an radioimmunology kit. The participants reported for stress symptoms after the shifts and filled a sleep diary. The effects of job task, shift, and time-of-day were analyzed by tests of between-subjects effects (SPSS). Cortisol retained the typical diurnal pattern with a highly significant effect of the shift. The job task and the shift interacted significantly. Higher cortisol values during the morning and night shifts in engineers working in direct transmissions were found. Their stress ratings were also higher, as well as the ratings of sleepiness and fatigue. The quality of sleep was worse in engineers working in direct transmissions. In conclusion, our data indicate that stress and fast backward-rotating shifts in sound engineers working in direct transmissions affect physiological stress markers such as cortisol and increase sleepiness, fatigue, and sleep problems.

Changes in nurses' decision making during a 12-h day shift.

PubMed

McClelland, L E; Switzer, F S; Pilcher, J J

2013-01-01

Although shift work is necessary in many health-care settings, research suggests that it can have detrimental effects on performance in health-care providers. To determine if a change in decision-making occurred across a 12-h day shift in a sample of registered nurses. The participants were nurses working a 12-h day shift (7 a.m.-7 p.m.) at a large hospital in the south-eastern USA. Participants completed a policy-capturing questionnaire, examining their likelihood of calling a physician in response to specific patient symptoms, at the beginning and end of the shift. They also completed self-report surveys on alertness, stress and sleepiness. Sixty-five nurses completed the study, an overall response rate of 41%. Participants significantly changed their decision-making policies from the beginning to the end of the work shift and also became significantly less alert and more stressed. However, there was no correlation between decision-making and reported alertness and stress. These results suggest that medical judgment in registered nurses changed from the beginning to the end of a 12-h day shift. One possible underlying mechanism responsible for the changes seen across the shift could be the ability to maintain attention, as suggested by the Controlled Attention Model. The current results expand upon previous research, indicating there are a variety of negative outcomes associated with shift work.

The effect of work shift configurations on emergency medical dispatch center response.

PubMed

Montassier, Emmanuel; Labady, Julien; Andre, Antoine; Potel, Gilles; Berthier, Frederic; Jenvrin, Joel; Penverne, Yann

2015-01-01

It has been proved that emergency medical dispatch centers (EMDC) save lives by promoting an appropriate allocation of emergency medical service resources. Indeed, optimal dispatcher call duration is pivotal to reduce the time gap between the time a call is placed and the delivery of medical care. However, little is known about the impact of work shift configurations (i.e., work shift duration and work shift rotation throughout the day) and dispatcher call duration. Thus, the objective of our study was to assess the effect of work shift configurations on dispatcher call duration. During a 1-year study period, we analyzed the dispatcher call durations for medical and trauma calls during the 4 different work shift rotations (day, morning, evening, and night) and during the 10-hour work shift of each dispatcher in the EMDC of Nantes. We extracted dispatcher call durations from our advanced telephone system, configured with CC Pulse + (Genesys, Alcatel Lucent), and collected them in a custom designed database (Excel, Microsoft). Afterward, we analyzed these data using linear mixed effects models. During the study period, our EMDC received 408,077 calls. Globally, the mean dispatcher call duration was 107 ± 45 seconds. Based on multivariate linear mixed effects models, the dispatcher call duration was affected by night work shift and work shift duration greater than 8 hours, increasing it by about 10 ± 1 seconds and 4 ± 1 seconds, respectively (both p < 0.001). Our study showed that there was a statistically significant difference in dispatcher call duration over work shift rotation and duration, with longer durations seen over night shifts and shifts over 8 hours. While these differences are small and may not have clinical significance, they may have implications for EMDC efficiency.

Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women.

PubMed

Vetter, Céline; Devore, Elizabeth E; Wegrzyn, Lani R; Massa, Jennifer; Speizer, Frank E; Kawachi, Ichiro; Rosner, Bernard; Stampfer, Meir J; Schernhammer, Eva S

2016-04-26

Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up. To determine whether rotating night shift work is associated with CHD risk. Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS [1988-2012]: N = 73,623 and NHS2 [1989-2013]: N = 115,535). Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2). Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty. During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). [table: see text] Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics.

Shift Work Disorder, Depression, and Anxiety in the Transition to Rotating Shifts: The Role of Sleep Reactivity

PubMed Central

Kalmbach, David A; Pillai, Vivek; Cheng, Philip; Arnedt, J Todd; Drake, Christopher L

2016-01-01

Objectives To investigate premorbid sleep reactivity as a vulnerability to incident shift work disorder and related changes in depression and anxiety following a transition to a rotating shifts work schedule. Methods This is a longitudinal study with two waves of data collection. The community-based sample included normal sleeping non-shift workers (N=96; 62.5% female; 47.9±13.3 yo) without a lifetime history of insomnia or baseline excessive daytime sleepiness who transitioned to rotating shift work one year later. Participants reported demographic characteristics, trait sleep reactivity on the Ford Insomnia Response to Stress Test, depression symptoms on the Quick Inventory of Depression Symptomatology, and anxiety symptoms on the Beck Anxiety Inventory. Shift work disorder was determined based on significant sleep disturbance and/or excessive sleepiness in the context of working a rotating shifts schedule. Results Analyses revealed that the odds were over five times greater for highly sleep reactive individuals to develop shift work disorder after transitioning to rotating shifts (OR=5.59, p=.04). Nearly 90% of shift work disorder sufferers were accurately identified as high risk at 1-y prior to disease onset. Furthermore, individuals who developed SWD reported greater increases in symptoms of depression and anxiety. Finally, analyses revealed significant indirect effects wherein high sleep reactivity increased risk for SWD, which led to greater severity of anxiety and depression symptoms. Conclusions The FIRST accurately identifies a focused target population in which the premorbid psychobiological processes complicit in SWD onset and progression, as well as shift work-related depression and anxiety changes, can be better investigated, thus improving future preventative efforts. PMID:26611952

Sleep Quality and Vigilance Differ Among Inpatient Nurses Based on the Unit Setting and Shift Worked.

PubMed

Surani, Salim; Hesselbacher, Sean; Guntupalli, Bharat; Surani, Sara; Subramanian, Shyam

2015-12-01

Sleepiness in nurses has been shown to impact patient care and safety. The objectives of this study are to measure sleep quality, sleepiness, fatigue, and vigilance in inpatient nurses and to assess how setting (intensive care unit versus the general floor) and shift worked (day versus night) affect these measures. Nurses from both the ICU and floor were included in the study. Participants completed questionnaires assessing self-reported sleep quality (Pittsburgh Sleep Quality Index, PSQI), sleepiness (Stanford Sleepiness Scale and Epworth Sleepiness Scale, ESS), and fatigue (Fatigue Severity Scale, FSS). Vigilance was measured by means of the psychomotor vigilance test (PVT), before and after a 12-hour duty shift. The ESS was abnormal in 22% of all nurses, the FSS was abnormal in 33%, and the global PSQI was abnormal in 63%. More ICU nurses than floor nurses reported abnormal sleep quality (component 5) on the PSQI. Sleep medication use (PSQI component 6) was higher in night shift nurses. The FSS was greater in night shift nurses. On preshift PVT testing, day-shift nurses overall provided faster mean reaction time (RT) than night-shift nurses. ICU nurses working the day shift made more than twice as many total errors and false starts than day shift floor nurses. Floor nurses demonstrated a significant decrease from preshift to postshift in the mean of the fastest 10% RT. Our data indicate that a significant number of inpatient nurses have impaired sleep quality, excessive sleepiness, and abnormal fatigue, which may place them at a greater risk of making medical errors and harming patients; these problems are especially pronounced in night shift workers. PVT results were inconsistent, but floor and day shift nurses performed better on some tasks than ICU and night shift nurses.

Direct and Nondirect Marathon Group Therapy and Internal---External Control

ERIC Educational Resources Information Center

Kilmann, Peter R.

1974-01-01

Investigates whether direct and nondirect therapist techniques within a 23-hour marathon format would differentially induce client shifts in locus of control. The no-treatment control group experienced a significant shift toward externality, while the marathon subjects did not fluctuate significantly from pretherapy to posttherapy. (Author)

Beyond reward prediction errors: the role of dopamine in movement kinematics

PubMed Central

Barter, Joseph W.; Li, Suellen; Lu, Dongye; Bartholomew, Ryan A.; Rossi, Mark A.; Shoemaker, Charles T.; Salas-Meza, Daniel; Gaidis, Erin; Yin, Henry H.

2015-01-01

We recorded activity of dopamine (DA) neurons in the substantia nigra pars compacta in unrestrained mice while monitoring their movements with video tracking. Our approach allows an unbiased examination of the continuous relationship between single unit activity and behavior. Although DA neurons show characteristic burst firing following cue or reward presentation, as previously reported, their activity can be explained by the representation of actual movement kinematics. Unlike neighboring pars reticulata GABAergic output neurons, which can represent vector components of position, DA neurons represent vector components of velocity or acceleration. We found neurons related to movements in four directions—up, down, left, right. For horizontal movements, there is significant lateralization of neurons: the left nigra contains more rightward neurons, whereas the right nigra contains more leftward neurons. The relationship between DA activity and movement kinematics was found on both appetitive trials using sucrose and aversive trials using air puff, showing that these neurons belong to a velocity control circuit that can be used for any number of purposes, whether to seek reward or to avoid harm. In support of this conclusion, mimicry of the phasic activation of DA neurons with selective optogenetic stimulation could also generate movements. Contrary to the popular hypothesis that DA neurons encode reward prediction errors, our results suggest that nigrostriatal DA plays an essential role in controlling the kinematics of voluntary movements. We hypothesize that DA signaling implements gain adjustment for adaptive transition control, and describe a new model of the basal ganglia (BG) in which DA functions to adjust the gain of the transition controller. This model has significant implications for our understanding of movement disorders implicating DA and the BG. PMID:26074791

Atypical hemispheric specialization for faces in infants at risk for autism spectrum disorder.

PubMed

Keehn, Brandon; Vogel-Farley, Vanessa; Tager-Flusberg, Helen; Nelson, Charles A

2015-04-01

Among the many experimental findings that tend to distinguish those with and without autism spectrum disorder (ASD) are face processing deficits, reduced hemispheric specialization, and atypical neurostructural and functional connectivity. To investigate the earliest manifestations of these features, we examined lateralization of event-related gamma-band coherence to faces during the first year of life in infants at high risk for autism (HRA; defined as having an older sibling with ASD) who were compared with low-risk comparison (LRC) infants, defined as having no family history of ASD. Participants included 49 HRA and 46 LRC infants who contributed a total of 127 data sets at 6 and 12 months. Electroencephalography was recorded while infants viewed images of familiar/unfamiliar faces. Event-related gamma-band (30-50 Hz) phase coherence between anterior-posterior electrode pairs for left and right hemispheres was computed. Developmental trajectories for lateralization of intra-hemispheric coherence were significantly different in HRA and LRC infants: by 12 months, HRA infants showed significantly greater leftward lateralization compared with LRC infants who showed rightward lateralization. Preliminary results indicate that infants who later met criteria for ASD were those that showed the greatest leftward lateralization. HRA infants demonstrate an aberrant pattern of leftward lateralization of intra-hemispheric coherence by the end of the first year of life, suggesting that the network specialized for face processing may develop atypically. Further, infants with the greatest leftward asymmetry at 12 months where those that later met criteria for ASD, providing support to the growing body of evidence that atypical hemispheric specialization may be an early neurobiological marker for ASD. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Asymmetries of the central sulcus in young adults: Effects of gender, age and sulcal pattern.

PubMed

Sun, Bo; Ge, Haitao; Tang, Yuchun; Hou, Zhongyu; Xu, Junhai; Lin, Xiangtao; Liu, Shuwei

2015-08-01

In this study, we clarified the gender and age-related asymmetries of the central sulcus (CS) in early adulthood using a parametric ribbon method. The CS was reconstructed and parameterized automatically from 3D MR images of 112 healthy right-handed subjects. The 3D anatomic morphology of the CS was presented using 5 sulcal parameters, including sulcal depth position-based profile (DPP), average depth (AD), average width (AW), top length (TL) and bottom length (BL). Asymmetry differences in DPPs were found in the medial and lateral part of the CS. In addition, significant gender differences were observed in the medial and middle parts of the right CS DPPs but scattered in the left side. We found leftward asymmetries of TL in males, but rightward asymmetries of AW in females. Males had a greater AW than females in the right hemisphere. Moreover, the females had bilateral longer TL and a longer left BL than did males. We also found significant age-related reductions in bilateral TL and increases in bilateral AW, with males presenting more obvious age-related change than females. There were sexual differences of the CS patterns, in which Type b was the most dominant sulcal pattern in males, whereas Type a was dominant in females. Three-way ANOVA revealed sexual and asymmetry changes of TL and BL among different CS patterns. Our findings indicate that the lateralization performances of the CS manifest as sexually and regionally different. In addition, it is suggested that males may undergo a faster progress of aging compared to females. Copyright © 2015 ISDN. Published by Elsevier Ltd. All rights reserved.

Representational neglect for words as revealed by bisection tasks.

PubMed

Arduino, Lisa S; Marinelli, Chiara Valeria; Pasotti, Fabrizio; Ferrè, Elisa Raffaella; Bottini, Gabriella

2012-03-01

In the present study, we showed that a representational disorder for words can dissociate from both representational neglect for objects and neglect dyslexia. This study involved 14 brain-damaged patients with left unilateral spatial neglect and a group of normal subjects. Patients were divided into four groups based on presence of left neglect dyslexia and representational neglect for non-verbal material, as evaluated by the Clock Drawing test. The patients were presented with bisection tasks for words and lines. The word bisection tasks (with words of five and seven letters) comprised the following: (1) representational bisection: the experimenter pronounced a word and then asked the patient to name the letter in the middle position; (2) visual bisection: same as (1) with stimuli presented visually; and (3) motor bisection: the patient was asked to cross out the letter in the middle position. The standard line bisection task was presented using lines of different length. Consistent with the literature, long lines were bisected to the right and short lines, rendered comparable in length to the words of the word bisection test, deviated to the left (crossover effect). Both patients and controls showed the same leftward bias on words in the visual and motor bisection conditions. A significant difference emerged between the groups only in the case of the representational bisection task, whereas the group exhibiting neglect dyslexia associated with representational neglect for objects showed a significant rightward bias, while the other three patient groups and the controls showed a leftward bisection bias. Neither the presence of neglect alone nor the presence of visual neglect dyslexia was sufficient to produce a specific disorder in mental imagery. These results demonstrate a specific representational neglect for words independent of both representational neglect and neglect dyslexia. ©2011 The British Psychological Society.

Armodafinil for treatment of excessive sleepiness associated with shift work disorder: a randomized controlled study.

PubMed

Czeisler, Charles A; Walsh, James K; Wesnes, Keith A; Arora, Sanjay; Roth, Thomas

2009-11-01

To assess the effect of armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (> or =3 months) shift work disorder (SWD) of moderate or greater severity. This 12-week, randomized controlled study was conducted at 42 sleep research facilities in North America from April 2 through December 23, 2004, and enrolled 254 permanent or rotating night shift workers with SWD. Entry criteria included excessive sleepiness during usual night shifts for 3 months or longer (corroborated by mean sleep latency of < or =6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency < or =87.5% during daytime sleep), and SWD that was judged clinically to be of moderate or greater severity. Patients received armodafinil, 150 mg, or placebo 30 to 60 minutes before each night shift. Physiologic sleep propensity during night shift hours, clinical impression of severity, patient-reported sleepiness, and cognitive function were assessed during laboratory night shifts at weeks 4, 8, and 12. Armodafinil significantly improved mean (SD) sleep latency from 2.3 (1.6) minutes at baseline to 5.3 (5.0) minutes at final visit, compared with a change from 2.4 (1.6) minutes to 2.8 (2.9) minutes in the placebo group (P<.001). Clinical condition ratings improved in more patients receiving armodafinil (79%) vs placebo (59%) (P=.001). As reported by patients' diaries, armodafinil significantly reduced sleepiness during laboratory nights (P<.001), night shifts at work (P<.001), and the commute home (P=.003). Armodafinil improved performance on standardized memory (P<.001) and attention (power, P=.001; continuity, P<.001) tests compared with placebo. Armodafinil was well tolerated and did not affect daytime sleep, as measured by polysomnography. In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention. clinicaltrials.gov Identifier: NCT00080288.

Health and Occupational Outcomes Among Injured, Nonstandard Shift Workers.

PubMed

Wong, Imelda S; Smith, Peter M; Mustard, Cameron A; Gignac, Monique A M

2015-11-01

This study compares health and occupational outcomes following a work-related injury for nonstandard and day-shift workers. National Population Health Survey data were used to explore outcomes 2 years post-work injury. Retrospective-matched cohort analyses examined main effects and interactions of shift schedule and work injury with changes in health, shift schedule, and labor force status. Models were adjusted for respondent characteristics, baseline health status, and occupational strength requirements. Injured nonstandard shift workers reported lower health utility index scores, compared with uninjured and injured daytime workers and uninjured nonstandard-shift workers. No significant interactions between shift and injury were found with schedule change and leaving the labor force. Injured nonstandard-shift workers are as likely to remain employed as other groups, but may be vulnerable in terms of diminished health.

Mandibular kinematic changes after unilateral cross-bite with lateral shift correction.

PubMed

Venancio, F; Alarcon, J A; Lenguas, L; Kassem, M; Martin, C

2014-10-01

The aim of this randomised prospective study was to evaluate the effects of slow maxillary expansion with expansion plates and Hyrax expanders on the kinematics of the mandible after cross-bite correction. Thirty children (15 boys and 15 girls), aged 7·1-11·8, with unilateral cross-bite and functional shift were divided into two groups: expansion plate (n = 15) and Hyrax expander (n = 15). Thirty children with normal occlusion (14 boys and 16 girls, aged 7·3-11·6) served as control group. The maximum vertical opening, lateral mandibular shift (from maximum vertical opening to maximum intercuspation, from rest position to maximum intercuspation and from maximum vertical opening to rest position) and lateral excursions were recorded before and 4 months after treatment. After treatment, the expansion plate group showed a greater lateral shift from rest position to maximum intercuspation than did the control group. The expansion plate patients also presented greater left/contralateral excursion than did the control group. Comparisons of changes after treatment in the cross-bite groups showed significant decreases in the lateral shift from the maximum vertical opening to maximum intercuspation and from the maximum vertical opening to rest position, a significant increase in the homolateral excursion and a significant decrease in the contralateral excursion in the Hyrax expander group, whereas no significant differences were found in the expansion plate group. In conclusion, the Hyrax expander showed better results than did the expansion plate. The Hyrax expander with acrylic occlusal covering significantly improved the mandibular lateral shift and normalised the range of lateral excursion. © 2014 John Wiley & Sons Ltd.