Logistic regression analysis was conducted to determine the effec

Logistic regression analysis was conducted to determine the effect of multiple variables on postoperative hyperperfusion.

RESULTS: Transient symptoms of CHS were observed in 3 patients. Cerebral hyperperfusion was detected in 12 patients (24%) as defined by method 1 and in 9 patients (18%) by method 2. Postoperative hyperperfusion occurred significantly more frequently

in patients with the steal phenomenon (regional cerebral selleck products vasoreactivity <= 0%; P = .001 by method 1 and P = .001 by method 2) and correlated with impaired preoperative regional cerebral vasoreactivity (P < .001). Logistic regression analysis revealed that the steal phenomenon was a significant risk factor Lonafarnib manufacturer for hyperperfusion as defined by both methods 1 (P = .009) and 2 (P = .03).

CONCLUSION: The incidence of cerebral blood flow-assessed postoperative hyperperfusion after EC-IC bypass for atherosclerotic occlusive cerebrovascular diseases was not rare. Post EC-IC bypass CHS could be reduced

by continuous, strict blood pressure control under sedation.”
“BACKGROUND: Limited dorsal myeloschisis (LDM) is a distinctive form of spinal dysraphism characterized by 2 constant features: a focal “”closed”" midline defect and a fibroneural stalk that links the skin lesion to the underlying cord. The embryogenesis is hypothesized to be incomplete disjunction between cutaneous and neural ectoderms, thus preventing complete midline skin closure and allowing persistence of a physical link (fibroneural stalk) between the disjunction site and the dorsal neural tube.

OBJECTIVE: To illustrate these features in 51 LDM patients.

METHODS: All patients were studied with magnetic resonance imaging or computed tomography myelography, operated on, and followed for a mean of 7.4 years.

RESULTS: There were 10 cervical, 13 thoracic, 6 thoracolumbar and 22 lumbar lesions. Two main types of skin lesion were saccular (21 patients),

consisting of a skin-base cerebrospinal fluid sac topped Inositol monophosphatase 1 with a squamous epithelial dome, and nonsaccular (30 patients), with a flat or sunken squamous epithelial crater or pit. The internal structure of a saccular LDM could be a basal neural nodule, a stalk that inserts on the dome, or a segmental myelocystocele. In nonsaccular LDMs, the fibroneural stalk has variable thickness and complexity. In all LDMs, the fibroneural stalk was tethering the cord. Twenty-nine patients had neurological deficits. There was a positive correlation between neurological grade and age, suggesting progression with chronicity. Treatment consisted of detaching the stalk from the cord. Most patients improved or remained stable.

The next frontier in MS therapeutics will supplement immunomodula

The next frontier in MS therapeutics will supplement immunomodulation with agents that check details directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.”
“Denoising is a fundamental early stage in 2-DE image analysis strongly influencing spot detection or pixel-based methods. A novel nonlinear

adaptive spatial filter (median-modified Wiener filter, MMWF), is here compared with five well-established denoising techniques (Median, Wiener, Gaussian, and Polynomial-Savitzky-Golay filters; wavelet denoising) to suggest, by means of fuzzy sets evaluation, the best denoising approach to use in practice. Although median filter and wavelet achieved the best performance in spike and Gaussian denoising Selleck QNZ respectively, they are unsuitable for contemporary removal of different types of noise, because

their best setting is noise-dependent. Vice versa, MMWF that arrived second in each single denoising category, was evaluated as the best filter for global denoising, being its best setting invariant of the type of noise. In addition, median filter eroded the edge of isolated spots and filled the space between close-set spots, whereas MMWF because of a novel filter effect (drop-off-effect) does not suffer from erosion problem, preserves the morphology of close-set spots, and avoids spot and spike fuzzyfication, an aberration encountered for almost Wiener filter. In our tests, MMWF was assessed as the best choice when the goal is to minimize spot edge aberrations while removing spike and Gaussian noise.”
“Purpose: We evaluated unrelated living kidney donation in the United States and examined the characteristics of unrelated donor-recipient pairs.

Materials and Methods: We accessed United Network for Organ Sharing files to identify adult living donor renal transplant recipients who received a transplant

between 1997 and 2007. We evaluated factors associated with unrelated donation and compared a composite index of the socioeconomic characteristics of donor and recipient ZIP Codes between living unrelated and living related renal transplantation pairs. Spousal pairs were categorized as living related.

Results: Of 39,168 adult renal transplant recipients 19% underwent living unrelated renal transplantation. These recipients were more likely white (vs black, Hispanic and other race OR 0.77-0.82, p < 0.05) and more highly educated (college vs less than high school OR 0.66, 95% CI 0.54-0.77), and more commonly received care at high volume transplant centers (vs lowest volume centers OR 0.89, 95% CI 0.82-0.95). Living unrelated renal transplantation recipients and donors lived in higher socioeconomic status index ZIP Codes than living related recipients (mean +/- SD recipients and donors 0.62 +/- 3.74 and 0.44 +/- 3.63 vs 0.03 +/- 3.85 and 0.

Ligand binding studies using intrinsic tryptophan fluorescence ha

Ligand binding studies using intrinsic tryptophan fluorescence have provided supporting evidence for the apparent preference of this enzyme to bind the beta(1 -> 6) disaccharide acceptor. However, we could not detect binding or Trichostatin A molecular weight gal actofuranosyltransferase activity with an n-octyl beta-D-Gal-(1 -> 4)-alpha-L-Rha acceptor, which mimics the reducing terminus of galactan in the mycobacterial cell wall. Conversely, after an extensive bioinformatics analysis

of the H37Rv genome, further cloning, expression and functional analysis of the Rv3792 open reading frame indicates that this protein affords galactofuranosyltransferase activity against such an acceptor and paves the way for a better understanding of galactan biosynthesis in Mycobacterium tuberculosis. (C) 2007 Elsevier Inc. All rights reserved.”
“Alcohol dependence (AD) is a common,

chronic, relapsing disorder. Compelling epidemiological evidence indicates that >50% of the risk for becoming alcoholic stems from genetic susceptibility and genetic studies have identified several risk genes. Alcohol intake alters gene expression patterns, thereby producing long-lasting cellular and molecular adaptations that might explain the development and maintenance of AD. The heterogeneous nature of AD indicates a complex etiology involving mechanisms related to motivational selleck inhibitor behavior, check details reward and learning, adaptations in signaling pathways owing to interactions between alcohol and target molecules, and chromatin remodeling. Emerging methodologies present opportunities to determine how alcohol might disrupt the synergistic

actions of molecular systems and to assess gene-environment interactions for elucidating the behavioral and physiological dysfunctions underlying AD.”
“For individuals with autism spectrum disorder or ‘ASD’ the ability to accurately process and interpret auditory information is often difficult. Here we review behavioural, neurophysiological and imaging literature pertaining to this field with the aim of providing a comprehensive account of auditory processing in ASD, and thus an effective tool to aid further research. Literature was sourced from peer-reviewed journals published over the last two decades which best represent research conducted in these areas. Findings show substantial evidence for atypical processing of auditory information in ASD at behavioural and neural levels. Abnormalities are diverse, ranging from atypical perception of various low-level perceptual features (i.e. pitch, loudness) to processing of more complex auditory information such as prosody. Trends across studies suggest auditory processing impairments in ASD are most likely to present during processing of complex auditory information and are more severe for speech than for non-speech stimuli.

In this study, we assess the effects of TAU pretreatment

In this study, we assess the effects of TAU pretreatment click here on the behavior of zebrafish in the open tank after acute 1% EtOH (v/v) exposure (20 and 60 min of duration) and on brain alcohol contents. The exposure for 20 min exerted significant anxiolytic effects, which were prevented by 42,150, and 400 mg/L TAU. Conversely, the 60-min condition induced depressant/sedative effects, in which the changes on vertical activity were associated to modifications

on the exploratory profile. Although all TAU concentrations kept locomotor parameters at basal levels, 150 mg/L TAU, did not prevent the impairment on vertical activity of EtOH[60]. Despite the higher brain EtOH content detected in the 60-min exposure, 42, 150, and 400 mg/L TAU attenuated the increase of alcohol content in EtOH[60] group. In conclusion, our data suggest that both protocols of acute EtOH exposure induce significant changes in the spatio-temporal behavior of zebrafish

and that TAU may exert a preventive role by antagonizing the effects induced by EtOH possibly due to its neuromodulatory role and also by decreasing brain EtOH levels. The hormetic dose-response of TAU on vertical exploration suggests a complex interaction between TAU and EtOH in the central nervous system. (C) 2012 Elsevier Ltd. All rights reserved.”
“Recent studies have revealed that E3 ubiquitin ligases have essential functions in the establishment of neuronal circuits. Strikingly, a common emerging theme in these studies is that spatial organization of E3 ubiquitin ligases plays a critical role in the control of neuronal learn more morphology and connectivity. E3 ubiquitin ligases localize to the nucleus, centrosome, Golgi apparatus, axon and

dendrite cytoskeleton, and synapses in neurons. Localization of ubiquitin ligases within distinct subcellular compartments may facilitate neuronal responses to extrinsic cues and the ubiquitination of local substrates. Here, we review the functions of neuronal E3 ubiquitin ligases at distinct subcellular locales and explore how they regulate neuronal morphology Urease and function in the nervous system.”
“Background: Although C-reactive protein (CRP) is significantly increased in patients with diabetic nephropathy, whether CRP exerts direct proinflammatory effects on human renal tubular epithelial cells (HK-2 cells) is still unclear. Methods: HK-2 cells were incubated with purified CRP at clinically relevant concentrations (0, 5, 10, 20 and 40 mu g/ml). The protein and transcript levels of thrombospondin-1 (TSP-1) and interleukin-6 (IL-6) were determined by ELISA and RT-PCR. Phosphorylation of p38MAPK was investigated through Western blot analysis in HK-2 cells induced by CRP. The activation of nuclear factor-kappa B (NF-kappa B) was studied via EMSA. A specific p38MAPK inhibitor (SB203580) and an NF-kappa B inhibitor (PDTC; pyrrolidine dithiocarbamate) were used to analyze the signal transduction in CRP induction.

These results showed that LPS may enhance the oxidative stress in

These results showed that LPS may enhance the oxidative stress induced by amorphous silica ENP to initiate cytotoxicity of these engineered nanoparticles.”

lead exposure is associated with decreased cognitive abilities and executive functioning localized within the prefrontal cortex. Several studies have observed stronger associations between blood lead measurements obtained later in life than earlier measures, but there are no imaging studies investigating the developmental trajectory of blood lead levels taken during childhood on adult gray matter volume. In this study, we recruited 157 adults (20.8 +/- 1.5 years of age) from the Cincinnati Lead 4EGI-1 in vitro Study to undergo high resolution volumetric magnetic resonance imaging. Adjusted voxel-wise regression analyses were performed for associations between adult gray matter volume loss and yearly mean blood lead levels from 1 to 6 years of age in the entire cohort and by sex. We observed significant inverse

associations between gray matter volume loss and annual mean blood lead levels from 3 to 6 years of age. The extent of prefrontal gray matter associated with yearly Tozasertib mean blood lead levels increased with advancing age of the subjects. The inverse associations between gray matter volume loss and yearly mean blood lead measurements were more pronounced in the frontal lobes of men than women. Analysis of women yielded significantly weaker associations between yearly mean blood lead levels and gray matter volume at all ages than either men or the combined cohort of men and women together. check These results suggest that blood lead concentrations obtained during later childhood demonstrate greater loss in gray matter volume than childhood mean or maximum values. The relationship between childhood blood lead levels and

gray matter volume loss was predominantly observed in the frontal lobes of males. This study demonstrates that maximum blood lead levels do not fully account for gray matter changes associated with childhood lead exposure, particularly in the frontal lobes of young men. (C) 2010 Elsevier Inc. All rights reserved.”
“The aim of this study was to examine the plasma, liver, and kidney status of vitamin A (retinol) and vitamin E (-tocopherol) in two groups of Greenland sled dogs (Canis familiaris), with a total number of 16 bitches and 8 pups. The dogs were fed either minke whale (Balaenoptera acuterostrata) blubber (exposed dogs) or uncontaminated (control group) porcine fat for up to 12 to 21 mo of age. The daily intake of 50-200 g whale blubber (mean: 112 g) constituted between 10.4 and 11.7 mu g/kg body weight Sigma organohalogen contaminants (OHC) (or between 4.6 and 6.1 mu g/kg body weight Sigma polychlorinated biphenyls [PCB]). Retinol was approximately 18% and -tocopherol 22% higher in the diet of the exposed dogs compared to controls.

MZR 150 mg was administered once a day After 6 months, the remis

MZR 150 mg was administered once a day. After 6 months, the remission rate was 72.7 % (2 subjects achieved complete remission, and

Nutlin3a 9 partial remission). After 3 and 6 months, significant reductions (p < 0.01) were obtained in 24-h proteinuria (g/day). In the subjects switched to MZR due to lack of efficacy with CTX, the dose was increased from MZR 150-200 mg due to inadequate improvement in proteinuria, and this dose escalation resulted in complete remission after 6 months. It is believed that this kind of dose escalation is one possible treatment option for lupus nephritis. In this study, no adverse events occurred in any of the subjects. We therefore concluded that this first use in China as remission induction therapy in lupus nephritis patients of MZR, which is recognized

as an effective maintenance therapy in Japan, was effective. The results also suggest that MZR could be effective in patients for whom other drugs have been insufficiently effective.”
“In recent years, scientific efforts on the topic “”gout”" have focused on pathogenetic aspects. This has opened new strategies of anti-inflammatory Selleckchem LY2835219 therapy and has improved urate-lowering therapy. So far, a scientometric analysis of the topic “”gout”" has not been generated despite an increased need for it in times of modified evaluation criteria for academic personnel and a subsequent tendency to co-authorship and author self-citation. The study aims to evaluate quality and quantity of scientific research dealing with the topic “”gout”" and to contribute to distinguish relevant research output. The current study uses scientometric methods and large-scale data analysis to evaluate quality

and quantity of scientific efforts in the field of “”gout.”" Data were gained from PubMed and ISI-Web. In the last 22 years (1990-2012), science 4,424 items were published by 71 countries, of which the USA have been the most productive supplier with 32 % of all publications, followed in considerable distance by the United Kingdom, Japan, Spain and Germany, respectively. The USA have established their position as center of international cooperation. The most prolific journals in the field of gout were “”Arthritis and Rheumatism,”" “”Annals of the Rheumatic diseases”" and the “”Journal of Rheumatology.”" Our analysis specifies the most productive authors and institutions engaged with the topic, the most successful international and national cooperation and the most prolific journals and subject areas. Nevertheless, scientometric indicators, such as h-index, citation rate and impact factor, commonly used for assessment of scientific quality, should be seen critically due to distortion by bias of self-citation and co-authorship.”
“Subclinical atherosclerosis has been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs of cardiovascular disease (CVD).

Intra-CeA R121919 blocked both excessive palatable food intake an

Intra-CeA R121919 blocked both excessive palatable food intake and anxiety-like behavior in Chow/Palatable rats, without affecting chow hypophagia. Conversely, intra-BlA R121919 reduced the chow hypophagia in Chow/Palatable rats, without affecting excessive palatable food intake or anxiety-like behavior. Intra-BNST treatment had no effect. The treatments did not modify the behavior of Chow/Chow rats. Immunohistochemistry revealed an increased number of CRF-positive cells in CeA-but not in BlA Volasertib mouse or BNST-of Chow/Palatable

rats, during both withdrawal and renewed access to the palatable diet, compared with controls. These results provide functional evidence that the CRF-CRF1 receptor system in CeA and BlA has a differential role in mediating maladaptive behaviors resulting from palatable diet cycling. Neuropsychopharmacology (2013)”
“Alpha interferon (IFN-alpha)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-alpha therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-alpha treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-alpha-induced miR-122 downregulation was only partly due to transcriptional

suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, C646 order efficiently inhibited miR-122 by binding and sequestering nearly miR-122 with its mRNA 3′-untranslated region (3′-UTR), indicating that this ISG is involved in IFN-alpha-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-alpha on miR-122 was completely abolished by blocking IFN-alpha-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-alpha-mediated HBV-inhibitory effects could be enhanced significantly

by blocking IFN-alpha-induced downregulation of miR-122. We therefore concluded that IFN-alpha-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-alpha. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-alpha and raise further potential interest in enhancing its anti-HBV efficacy.”
“Clinical proteomics faces extremely complex and variable data. Here, we present an updated version of the Griss Proteomics Database Engine (GPDE): A free biological proteomic database specifically designed for clinical proteomics and biomarker discovery (http://gpde.sourceforge.net). It combines experiments based on investigated cell types thereby supporting customizable biological meta-analyses. Through the new features described here, the GPDE now became a powerful yet easy-to-use tool to support the fast identification and reliable evaluation of biomarker candidates.

Both the severity and incidence of spontaneous recurrent seizures

Both the severity and incidence of spontaneous recurrent seizures tended to progress with time, and

their incidence increased from ASP2215 ic50 50% to 87.5% at 5 and 7 months, respectively. Morphometric analysis and stereologic assessment of hilar neurons performed after video-EEG monitoring revealed atrophy of temporal brain structures, enlargement of lateral ventricles, and loss of hilar neurons in both age groups. In P12 rats, morphologic damage also tended to progress over time. Performance of animals in the Morris water maze correlated with the severity of damage, but not with seizure parameters. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The ability to form spatial representations of object locations is an important component of successful spatial navigation. Evidence from behavioral studies

suggests that environmental features that have a salient coordinate axis (e.g., a rectangular building or a geometrical room) may provide a reference frame for the encoding of object-location information. Here we used functional magnetic resonance imaging (fMRI) to determine the brain networks engaged when object-location representations are stored with respect learn more to an extrinsic reference frame. Participants learned the layout of an object array in an active, virtual-navigation paradigm. A square mat positioned on the floor of the virtual arena acted as the extrinsic reference frame. Knowledge of the spatial arrangement of the object array was probed while participants PTK6 underwent fMRI, using a spatial judgment task that required them to imagine orientations of the learned array that were either aligned or misaligned with the geometry of the mat. Consistent with previous findings, participants responded faster and were more accurate when the imagined orientation was aligned, as opposed to misaligned, with the extrinsic reference frame. Analysis of the fMRI data revealed important

differences in brain activity between the two conditions. Significantly greater activity was observed in the aligned condition compared with the misaligned condition across a bilateral network of brain areas that included the inferior occipital gyri, inferior and middle temporal gyri, and fusiform gyri. By contrast, activity in the misaligned condition was significantly greater than in the aligned condition in bilateral dorsolateral prefrontal and anterior cingulate cortex, and in the right anterior prefrontal and anterior insular cortex. These results suggest that retrieval of spatial locations that are aligned with an extrinsic reference frame involve direct access to detailed and accurate representations within the ventral visual pathway, whereas spatial locations that are misaligned with this reference frame are only weakly represented and require active inferential processes through the recruitment of prefrontal cortical networks.

Fish and mammalian IFN-gamma thus show strikingly similar gene in

Fish and mammalian IFN-gamma thus show strikingly similar gene induction properties. Interestingly, the antiviral activity of IFN-gamma against IPNV and SAV3 and its ability to induce Mx and ISG15 markedly decreased

in the presence of neutralizing antiserum against IFNa1. In contrast, antiIFNa1 had no effect on the induction of IRF-1 and IP-10 by IFN-gamma. This suggests that the antiviral activity of IFN-gamma is partially dependent on IFNa induction. However, because antiIFNa1 could not abolish the IFN-gamma-mediated induction of Mx and ISG15 completely, IFN-gamma may possibly also induce such genes directly.”
“Transcranial Direct Current Stimulation (tDCS) enhances performance on working memory tasks. However, such effects may be dependent on modulation of specific aspects of working memory. We therefore tested the hypothesis that tDCS improves selective attention in the context of a Sternberg task. Subjects C646 molecular weight had to maintain a memory set while responding to distracter stimuli. Probes consisted of one item from the memory set, and one item that could have been presented as a distracter. TDCS was found to improve reaction time significantly only when Thiazovivin solubility dmso the incorrect choice had been a distracter stimulus. The results thus support the notion that tDCS effects on working memory might be mediated by a specific effect on selective attention. (C) 2012

Elsevier Ireland Ltd. All rights reserved.”
“Soft X-ray tomography (SXT) is ideally suited to imaging sub-cellular architecture and organization, particularly in eukaryotic cells. SXT is similar in concept to the

well-established medical diagnostic technique computed axial tomography (CAT), except SXT is capable of imaging with a spatial resolution of 50 nm, or better. In SXT, cells are imaged using photons from a region of the spectrum known as the ‘water window’. This results in quantitative, high-contrast images of intact, fully hydrated cells without Adenosine triphosphate the need to use contrast-enhancing agents. The cells that are visualized are in close-to-native, fully functional state. The utility of SXT has recently been enhanced by the development of high numerical aperture cryogenic light microscopy for correlated imaging. This multi-modal approach allows labelled molecules to be localized in the context of a high-resolution 3-D tomographic reconstruction of the cell.”
“Adolescents and adult rodents have differing sensitivities to the acute effects of ethanol on a variety of behavioral and electrophysiological measures. Often, these differences are revealed using high ethanol doses and consequently little is known about these age-related effects using lower ethanol doses. We sought to determine if low-dose ethanol produces differential effects on cognition and motor behavior in adolescent and adult rats.

Hence, the signaling mechanism of muscarinic Ca(V)2 1 channel mod

Hence, the signaling mechanism of muscarinic Ca(V)2.1 channel modulation has

remained elusive. The present paper shows that inactivation of phospholipase C (PLC) abolishes this modulation while inhibition of phosphoinositide kinases, PI-3K and PI-4K, prevents its reversibility, suggesting that the reconstitution of muscarinic modulation depends on phosphoinositide rephosphorylation. In support of this hypothesis, the supply of intracellular phosphatidylinositol (4,5) bisphosphate [PI(4,5)P-2] blocked all muscarinic modulation of this channel. The results indicate selleck screening library that muscarinic M-1 modulation of Ca(V)2.1 Ca2+ channels in these neurons involves phosphoinositide SIS3 mouse hydrolysis. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The Claudication: Exercise vs Endoluminal Revascularization (CLEVER) Study is a prospective multicenter randomized clinical trial designed to compare the relative clinical and cost-effectiveness of invasive revascularization with stents to supervised exercise rehabilitation in a cohort with moderate to severe claudication due to aortoiliac insufficiency.

The study is currently enrolling at twenty-eight sites in the US and Canada. Enrollment of 217 participants is planned, with data collected at baseline, six months, and 18 months. The primary study endpoint is maximum walking duration (MWD) on a graded treadmill test; secondary

endpoints include community-based walking, markers of cardiovascular disease risk (body mass index, waist circumference, blood pressure, lipid profile, glucose tolerance, and plasma fibrinogen), health-related quality of life, and cost effectiveness. There are currently sixty randomized participants; recruitment is projected to end in July 2010 and final study results reported in June 2012. (J Vase Surg 2009;50:942-5.)”
“Relapse Selleckchem Lenvatinib to drug craving is problematic in treatment for drug abuse. Evidence suggests inactivation of dopaminergic neurotransmission during drug withdrawal. Meanwhile, a tryptamine analogue, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], has been reported to enhance electrical stimulation of monoamine release. This study examined the effect of (-)-BPAP on reinstatement of methamphetamine-seeking behavior in an animal model of relapse to drug abuse. Rats were trained to i.v. self-administer methamphetamine paired with a light and tone (methamphetamine-associated cues) under a fixed-ratio 1 schedule of reinforcement for 10 days. After extinction session under saline infusions without cues, a reinstatement test under saline infusions was begun. Reinstatement induced by methamphetamine-associated cues or methamphetamine-priming injections was attenuated by repeated administration of (-)BPAP during the extinction phase.