bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrimination and the Implicit Association Test
Authors: Rudman Laurie A. , Ashmore Richard D.
Published: July 2007

Prejudice researchers have been criticized for failing to assess behaviors that reflect overtly hostile actions (i.e. racial animus; Arkes & Tetlock, 2004; Mackie & Smith, 1998). Two studies sought to begin to fill this gap in the implicit literature by showing that scores on the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) are linked to harmful intergroup behaviors. In Study 1, the IAT predicted self-reported racial discrimination, including verbal slurs, exclusion, and physical harm. In Study 2, the IAT predicted recommended budget cuts for Jewish, Asian, and Black student organizations (i.e. economic discrimination). In each study, evaluative stereotype (but not attitude) IATs predicted behaviors even after controlling for explicit attitudes. In concert, the findings suggest that implicit stereotypes are more predictive of overtly harmful actions than implicit attitudes in the intergroup relations domain.
What Do We Think About Muslims? The Validity of Westerners' Implicit Theories About the Associations Between Muslims' Religiosity, Religious Identity, Aggression Potential, and Attitudes Toward Terrorism
Authors: Fischer Peter , Greitemeyer Tobias , Kastenmüller Andreas
Published: July 2007

In a series of three studies, we investigated the validity of implicit theories that the German public holds regarding Muslims. German participants expected Muslims to be more aggressive than Christians, and therefore be more supportive of terrorism than Christians. Furthermore, Muslims were assumed to be more intrinsically religious and to hold a stronger identity with their religion than Christians (Study 1). However, self-assessment surveys of Muslims and Christians in the Commonwealth of Independent States (CIS: ex-Soviet Union) revealed that Muslims were not more aggressive, more intrinsically religious, or more supportive of terrorism than Christians. In contrast, Muslims reported a stronger religious identification than Christians (Study 2). Correspondingly, threat to religious identity was found to affect only Muslims', but not Christians', attitudes toward terrorism conducted by outgroup perpetrators. In contrast to Germans' implicit theories regarding Muslims, it was the importance of religious identity and not increased aggression potential that mediated this effect (Study 3).
Perceptions and Metaperceptions of Negative Evaluation: Group Composition and Meta-Accuracy in a Social Relations Model
Authors: Santuzzi Alecia M.
Published: July 2007

This study examined whether socially stigmatized individuals (cigarette smokers) use unique person perception strategies during interaction with out-group individuals (nonsmokers), as well as implications for meta-accuracy. Undergraduate students ( N = 104) were divided into groups of four, representing one of three compositions: all smokers, all nonsmokers, or two smokers with two nonsmokers. Participants interacted with each group member, evaluated each other, and guessed partners' evaluations of themselves (metaperceptions). Contrary to past findings, smokers' metaperceptions of out-group members were not consistent across targets. Instead, smokers' metaperceptions were influenced by the smoking status of interaction partners. Moreover, smokers interacting with nonsmokers were least accurate in their metaperceptions, compared to other dyad combinations. Connections between metaperception and meta-accuracy are discussed.
Is Compensation Enough? Relational Concerns in Responding to Unintended Inequity
Authors: Okimoto Tyler G. , Tyler Tom R.
Published: July 2007

Traditional justice models suggest that monetary compensation is an adequate response to unintended distributive harm. This perspective is widely accepted in real world settings, and is manifested in policies ranging from worker compensation to the court-based tort system. Drawing on the arguments from relational models of authority, we hypothesize that compensation for losses may be viewed by victims as an inadequate response to the situation, even when those losses are accidental and not the result of intentional harm. In four experimental studies, respondents were asked to react to the receipt of monetary compensation for accidental distributive inequities under varying degrees of relational concern. Results indicate that judgments about the favorability of compensation are only one aspect of people's reaction to responses to harm. In each case, victims displayed more favorable reactions toward the group when compensation was supplemented by relational concern.
Structural properties of pulsed laser deposited zinc oxide thin films annealed at various temperatures
Authors: Rusop M. , Uma K. , Soga T. , Jimbo T.
Published: July 2007

Zinc oxide (ZnO) thin films were prepared by pulsed laser deposition (PLD) technique using XeCl excimer laser with a wavelength of 308 nm at room temperature on quartz and single crystal silicon (100) substrates. The oxygen gas pressure was set at 6 torr during the deposition. The deposited films were post-heat treated (HT) in air at different annealing temperatures (ATs) for 30 min. The X-ray diffraction (XRD), optical and electrical properties were measured to study the properties of the films as a function of AT. XRD analysis showed that the strength of (002) peak increases and full width at the half maximum (FWHM) value decreases as the AT increases from 200 to 600°C. The films HT at higher AT of ∼600°C showed dominant c axis oriented hexagonal wurtize crystal structure. The films HT at 600°C exhibit high average transmittance of ∼85% in the visible region and very sharp absorption edge at 376 nm with energy band gap of ∼3·46 eV. Electrical measurement indicates that the resistivity of films decreases with the AT up to 600°C, after which there is an increase at higher AT. The complex of hydrogen defect and oxygen vacancy in the ZnO films may be the reason for low conductivity in undoped ZnO films.
Tribological properties of surface engineered hot work tool steel for aluminium extrusion dies
Authors: Pellizzari M. , Zadra M. , Molinari A.
Published: July 2007

A tribological test aimed at the simulation of aluminium hot extrusion was performed. A 6082-Al disc, induction heated up to a maximum surface temperature of 350°C, is allowed to rotate against a conformal hot work steel block, simulating the extrusion die. The test simulates the wear mechanism observed under in service conditions. After an initial period, the hot plasticised Al progressively adheres to the steel counterpart thus allowing direct Al–Al contact. The high shear stresses given by the strong adhesion produce the nucleation of deep cracks which strongly deteriorate the surface of the steel by delamination. Hot work tool steel (AISI H11) is employed as extrusion dies. Salt bath nitriding (Tenifer) is usually carried out to improve wear resistance. The possible application of PVD (CrN, TiAlN) and CVD (TiC + TiN) hard coatings, exhibiting lower compatibility versus Al, has been evaluated in the present work. The occurrence of two distinct damage regimes was detected. Regime 1 shows minor excursions of the friction coefficient μ and is followed by regime 2 which is characterised by fully plastic Al–Al contact, with large fluctuations of μ. A time to transition tT has been identified as indicative of the ability of a surface layer in delaying the occurrence of regime 2. tT is correlated to the chemical compatibility of the surface layer (compound layer, PVD or CVD coating) versus Al. Furthermore, tT is related to the mechanical stability of the surface layer. A generalised and severe form of wear is displayed by nitrided steel while a localised and less severe form of wear is displayed by duplex treated, nitriding + PVD steel. No wear traces were observed by CVD TiC + TiN coated steel, providing the best performance among the surface treatment investigated.
Paste boriding process: Evaluation of boron mobility on borided steels
Authors: Campos I. , Ramírez G. , Figueroa U. , Velázquez C. Villa
Published: July 2007

The present study evaluates the boron mobility at the material surface of borided steels AISI 1045 and M2 during the paste boriding process. This surface hardening technique produces two characteristic phases on the material, FeB, Fe2B and a transition zone, denominated diffusion zone, in the layer/substrate interface. The thermochemical treatment was performed at three different temperatures: 1193, 1223, 1273 K and two treatment times: 2 and 6 h for the 1045 steel, and 1223, 1253 and 1273 K with the same treatment times for M2 steel, modifying the boron potentials in equilibrium at the substrates surfaces. By using the mass balance equation, and assuming a linear concentration profile at the interfaces, the new model determined the diffusion coefficients of boron in the phases formed at the surface of the substrates, included the diffusion zone for both steels.
Heat treated anodised titanium surfaces showing enhanced photocatalytic inhibition of microbial fouling
Authors: Gopal J. , George R. P. , Muraleedharan P. , Kalavathi S. , Mangamma G. , Khatak H. S.
Published: July 2007

Titanium, an otherwise perfect condenser tube material in sea water applications, is challenged by the problem of severe biofouling. Anatase, one of the two commercially important crystalline forms of titanium dioxide, possesses excellent photocatalytic activity (PCA). It has been shown in the earlier studies by the authors that anodisation of titanium produces anatase type of TiO2 capable of photocatalytic inhibition of microbial adhesion under near UV light illumination. The present study investigates the influence of anodising voltage and anodising time on the photocatalytic inhibition of Pseudomonas sp., a frequent coloniser of natural biofilms formed on titanium surfaces. The effect of heat treatment of anodised surfaces on PCA was also studied. The results showed that heat treatment resulted in a significant enhancement of PCA. The surface oxide was characterised using glancing incidence X-ray diffraction and atomic force microscopy and the results indicate a marked increase in the cystallinity of the anatase film on the heat treated anodised surfaces. Attempts have also been made to understand the mechanism underlying the photocatalytic inactivation of the bacterial cells on TiO2 surfaces by studying their growth characteristics.
Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27
Authors: Brender Christine , Tannahill Gillian M. , Jenkins Brendan J. , Fletcher Joel , Columbus Ruth , Saris Christiaan J. M. , Ernst Matthias , Nicola Nicos A. , Hilton Douglas J. , Alexander Warren S. , Starr Robyn
Published: July 2007

Suppressor of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine responses. SOCS3 is expressed in peripheral T cells, and recent reports have suggested that overexpression of SOCS3 modulates antigen- and/or costimulation-induced T-cell activation. To study the role of SOCS3 in the regulation of T-cell activation, we used a conditional gene-targeting strategy to generate mice that lack SOCS3 in T/natural killer T cells (Socs3ΔLck/ΔLck mice). SOCS3-deficient CD8 T cells showed greater proliferation than wild-type cells in response to T-cell receptor (TCR) ligation despite normal activation of signaling pathways downstream from TCR or CD28 receptors. Signaling in response to the gp130 cytokines interleukin (IL)–6 and IL-27 was prolonged in Socs3ΔLck/ΔLck T cells, and T cells from gp130Y757F/Y757F mice, in which the SOCS3-binding site on gp130 is ablated, showed a striking similarity to SOCS3-deficient CD8 T cells. Although the proliferative defect of Socs3ΔLck/ΔLck T cells was not rescued in the absence of IL-6, suppression of IL-27 signaling was found to substantially reduce anti-CD3–induced proliferation. We conclude that enhanced responses to TCR ligation by SOCS3-deficient CD8 T cells are not caused by aberrant TCR-signaling pathways but, rather, that increased IL-27 signaling drives unregulated proliferation in the absence of SOCS3.
Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo
Authors: Zennadi Rahima , Moeller Benjamin J. , Whalen Erin J. , Batchvarova Milena , Xu Ke , Shan Siqing , Delahunty Martha , Dewhirst Mark W. , Telen Marilyn J.
Published: July 2007

Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial αvβ3 integrin. To determine the contribution of LW activation to vaso-occlusive events in vivo, we investigated whether in vitro treatment of SS RBCs by epinephrine resulted in vaso-occlusion in intact microvasculature after RBC infusion into nude mice. Epinephrine enhanced human SS but not normal RBC adhesion to murine endothelial cells in vitro and to endothelium in vivo, promoting vaso-occlusion and RBC organ sequestration. Murine sickle RBCs also responded to epinephrine with increased adhesion to postcapillary endothelium in nude mice. Epinephrine-induced SS RBC adhesion, vaso-occlusion, and RBC organ trapping could be prevented by the β-adrenergic receptor (β-AR) antagonist, propranolol. Infusion of soluble recombinant LW also significantly reduced adhesion and vaso-occlusion. In addition, epinephrine-treated SS RBCs induced activation of murine leukocyte adhesion to endothelium as well. We conclude that LW activation by epinephrine via β-AR stimulation can promote both SS RBC and leukocyte adhesion as well as vaso-occlusion, suggesting that both epinephrine and LW play potentially pathophysiological roles in SCD.
Phenotypic alterations in type II alveolar epithelial cells in CD4+ T cell mediated lung inflammation
Authors: Gereke Marcus , Gröbe Lothar , Prettin Silvia , Kasper Michael , Deppenmeier Stefanie , Gruber Achim D , Enelow Richard I , Buer Jan , Bruder Dunja
Published: July 2007

Background

Although the contribution of alveolar type II epithelial cell (AEC II) activities in various aspects of respiratory immune regulation has become increasingly appreciated, our understanding of the contribution of AEC II transcriptosome in immunopathologic lung injury remains poorly understood. We have previously established a mouse model for chronic T cell-mediated pulmonary inflammation in which influenza hemagglutinin (HA) is expressed as a transgene in AEC II, in mice expressing a transgenic T cell receptor specific for a class II-restricted epitope of HA. Pulmonary inflammation in these mice occurs as a result of CD4+ T cell recognition of alveolar antigen. This model was utilized to assess the profile of inflammatory mediators expressed by alveolar epithelial target cells triggered by antigen-specific recognition in CD4+ T cell-mediated lung inflammation.

Methods

We established a method that allows the flow cytometric negative selection and isolation of primary AEC II of high viability and purity. Genome wide transcriptional profiling was performed on mRNA isolated from AEC II isolated from healthy mice and from mice with acute and chronic CD4+ T cell-mediated pulmonary inflammation.

Results

T cell-mediated inflammation was associated with expression of a broad array of cytokine and chemokine genes by AEC II cell, indicating a potential contribution of epithelial-derived chemoattractants to the inflammatory cell parenchymal infiltration. Morphologically, there was an increase in the size of activated epithelial cells, and on the molecular level, comparative transcriptome analyses of AEC II from inflamed versus normal lungs provide a detailed characterization of the specific inflammatory genes expressed in AEC II induced in the context of CD4+ T cell-mediated pneumonitis.

Conclusion

An important contribution of AEC II gene expression to the orchestration and regulation of interstitial pneumonitis is suggested by the panoply of inflammatory genes expressed by this cell population, and this may provide insight into the molecular pathogenesis of pulmonary inflammatory states. CD4+ T cell recognition of antigen presented by AEC II cells appears to be a potent trigger for activation of the alveolar cell inflammatory transcriptosome.
An economic model of long-term use of celecoxib in patients with osteoarthritis
Authors: Loyd Michael , Rublee Dale , Jacobs Philip
Published: July 2007

Background

Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA) have produced conflicting results. The recent controversy over the cardiovascular (CV) risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in a population of 60-year-old osteoarthritis (OA) patients with average risks of upper gastrointestinal (UGI) complications who require chronic daily NSAID therapy.

Methods

We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY) gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events.

Results

Our main findings were: 1) the base model incremental cost-effectiveness ratio (ICER) for celecoxib versus nsNSAIDs was $31,097 per QALY; 2) the ICER per QALY was $19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3) the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death) risks with base model assumptions.

Conclusion

Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.
Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma
Authors: Yu Decai , Zhuang Linyuan , Sun Xitai , Chen Jun , Yao Yongzhong , Meng Kui , Ding Yitao
Published: July 2007

Background

Endoglin (CD105) has been considered a prognostic marker for hepatocellular carcinoma (HCC), and widely used as an appropriate targeting for antiangenesis therapy in some cancers. Our aim was to evaluate the distribution and expression of CD105 in the liver of patients with HCC, and to discuss whether CD105 may be used as an appropriate targeting for antiangenesis therapy in HCC.

Methods

Three parts of liver tissues from each of 64 patients with HCC were collected: tumor tissues (TT), adjacent non-tumor (AT) liver tissues within 2 cm, and tumor free tissues (TF) 5 cm far from the tumor edge. Liver samples from 8 patients without liver diseases served as healthy controls (HC). The distribution and expression of CD105 in tissues were evaluated by immunohistochemistry, Western blotting analysis, and real-time PCR. HIF-1alpha and VEGF165 protein levels in tissues were analyzed by Immunohistochemistry and Western blotting analysis or ELISA.

Results

CD105 was positively stained mostly in a subset of microvessels 'endothelial sprouts' in TT of all patients while CD105 showed diffuse positive staining, predominantly on hepatic sinus endothelial cells in the surrounding of draining veins in TF and AT. The mean score of MVD-CD105 (mean ± SD/0.74 mm2) was 19.00 ± 9.08 in HC, 153.12 ± 53.26 in TF, 191.12 ± 59.17 in AT, and 85.43 ± 44.71 in TT, respectively. Using a paired t test, the expression of CD105 in AT and TF was higher than in TT at protein (MVD, p = 0.012 and p = 0.007, respectively) and mRNA levels (p < 0.001 and p = 0.009, respectively). Moreover, distribution and expression of CD105 protein were consistent with those of HIF-1alpha and VEGF165 protein in liver of patients with HCC. The level of CD105 mRNA correlated with VEGF165 level in TF (r = 0.790, p = 0.002), AT (r = 0.723, p < 0.001), and TT (r = 0.473, p = 0.048), respectively.

Conclusion

It is demonstrated that CD105 was not only present in neovessels in tumor tissues, but also more abundant in hepatic sinus endothelium in non-tumor tissues with cirrhosis. Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.
Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis
Authors: Sow Fatoumata B , Florence William C , Satoskar Abhay R , Schlesinger Larry S , Zwilling Bruce S , Lafuse William P
Published: July 2007

Hepcidin is an antimicrobial peptide produced by the liver in response to inflammatory stimuli and iron overload. Hepcidin regulates iron homeostasis by mediating the degradation of the iron export protein ferroportin 1, thereby inhibiting iron absorption from the small intestine and release of iron from macrophages. Here, we examined the expression of hepcidin in macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis. Stimulation of the mouse RAW264.7 macrophage cell line and mouse bone marrow-derived macrophages with mycobacteria and IFN-γ synergistically induced high levels of hepcidin mRNA and protein. Similar results were obtained using the human THP-1 monocytic cell line. Stimulation of macrophages with the inflammatory cytokines IL-6 and IL-β did not induce hepcidin mRNA expression. Iron loading inhibited hepcidin mRNA expression induced by IFN-γ and M. avium, and iron chelation increased hepcidin mRNA expression. Intracellular protein levels and secretion of hepcidin were determined by a competitive chemiluminescence ELISA. Stimulation of RAW264.7 cells with IFN-γ and M. tuberculosis induced intracellular expression and secretion of hepcidin. Furthermore, confocal microscopy analyses showed that hepcidin localized to the mycobacteria-containing phagosomes. As hepcidin has been shown to possess direct antimicrobial activity, we investigated its activity against M. tuberculosis. We found that hepcidin inhibited M. tuberculosis growth in vitro and caused structural damage to the mycobacteria. In summary, our data show for the first time that hepcidin localizes to the phagosome of infected, IFN-γ-activated cells and has antimycobacterial activity.
Replication and Identification of Novel Variants at TCF7L2 Associated with Type 2 Diabetes in Hong Kong Chinese
Authors: Ng Maggie C. Y. , Tam Claudia H. T. , Lam Vincent K. L. , So Wing-Yee , Ma Ronald C. W. , Chan Juliana C. N.
Published: July 2007

Objective: Variations at a large linkage disequilibrium (LD) block of transcription factor 7-like 2 gene (TCF7L2) were reported to be associated with type 2 diabetes (T2D) in Icelandic, Danish and European-American populations and further replicated in other populations of European, African, and Asian ancestries. However, data for Chinese and comprehensive survey of the whole gene are lacking.

Design: We attempted to examine 22 tagging single-nucleotide polymorphisms (SNPs) spanning across the TCF7L2 gene for association with T2D in Hong Kong Chinese. We first studied a case-control sample involving 433 hospital cases with familial early-onset T2D and 419 normal controls and further studied the associated SNPs in 450 members of 142 diabetic families.

Results: Two of the previously reported risk alleles at rs11196205 (C) and rs7903146 (T) were rare in Chinese (0.013 and 0.024, respectively, in controls). Rs11196205 was associated with T2D [odds ratio (OR) [95% confidence interval (CI)] = 2.11 (1.04–4.26)], whereas the association for rs7903146 [OR (95% CI) = 1.27 (0.71–2.29)] was not significant in the case-control sample. Interestingly, another SNP (rs11196218 G allele) located in adjacent LD block conferred independent risk for T2D [OR (95%CI) =1.43 (1.14–1.79)] and contributed high-population attributable risk of 42%. The association finding of rs11196218 and its haplotype for T2D was also replicated in the family sample (P < 0.05).

Conclusions: Our results are consistent with others’ findings that variations at TCF7L2 contribute to T2D, including Chinese. The presence of association signals spanning several LD blocks warrants further examination of extended regions to reveal the causal variant(s) for this important T2D gene.
Thyroid Echogenicity Predicts Outcome of Radioiodine Therapy in Patients with Graves’ Disease
Authors: Marković Vinko , Eterović Davor
Published: July 2007

Context: Despite accounting for variations in gland size and iodine kinetics, the success of radioiodine therapy in patients with Graves’ disease remains moderately common and unpredictable.

Objectives: We hypothesized that hypoechogenic glands, with large, densely packed cells, are more radiosensitive than normoechogenic glands, in which much radiation is wasted on more abundant colloid. We evaluated this hypothesis in a cohort of patients with Graves’ disease.

Design: This was a prospective trial of patients recruited during 4 yr and followed up 1 yr after radioiodine therapy.

Setting: This trial was held in a university hospital-outpatient clinic.

Patients: A total of 177 consecutive patients with first presentation of Graves’ disease (28 males), 23–76 yr old, who relapsed after antithyroid therapy were included in the study.

Intervention: The patients were assigned to an ablative target-absorbed dose of 200 Gy (n = 78) or randomly to 100 or 120 Gy of nonablative dose (n = 99).

Main Outcome Measures: The measures were incidences of hyperthyroidism, euthyroidism, and hypothyroidism at 12-month follow-up.

Results: At follow-up there were 25 hyperthyroid, 44 euthyroid, and 108 hypothyroid patients. Compared with 96 patients with a hypoechogenic gland, in 81 patients with a normoechogenic gland, there were more hyperthyroid (22 vs. 7%) and euthyroid (41 vs. 11%), but less hypothyroid outcomes (37 vs. 81%; P < 0.0001). The other independent predictor of increased radioresistance was the large gland volume.

Conclusion: In patients with Graves’ disease, normoechogenic and large glands are associated with increased radioresistance.
Selective Regulation of Somatostatin Receptor Subtype Signaling: Evidence for Constitutive Receptor Activation
Authors: Ben-Shlomo Anat , Pichurin Oxana , Barshop Nicole J. , Wawrowsky Kolja A. , Taylor John , Culler Michael D. , Chesnokova Vera , Liu Ning-Ai , Melmed Shlomo
Published: July 2007

Anterior pituitary hormone secretion is under tonic suppression by hypothalamic somatostatin signaling through somatostatin receptor subtypes (SSTs). Because some hormonal axes are known to be abnormally regulated by ligand-independent constitutively active G protein-coupled receptors, we tested pituitary SSTs for selective constitutive signaling. We therefore differentially silenced endogenous SST2, SST3, and SST5 in somatostatin-sensitive ACTH-secreting mouse AtT-20 pituitary corticotroph cells using small inhibitory RNA (siRNA) and analyzed downstream SSTs-regulated pathways. Transfection with siRNA reduced specific receptor subtype mRNA expression up to 82%. Specificity of receptor silencing was validated against negative controls with different gene-selective siRNAs, concordance of mRNA and cAMP changes, reduced potency of receptor-selective agonists, and phenotype rescue by overexpression of the silenced receptor. Mouse SST3 > SST5 > SST2 knockdown increased basal cAMP accumulation (up to 200%) and ACTH secretion (up to 60%). SST2- and SST5-selective agonist potencies were reduced by SST3- and SST5-silencing, respectively. SST5 > SST2 = SST3 silencing also increased basal levels of ERK1/2 phosphorylation. SST3- and SST5-knockdown increased cAMP was only partially blocked by pertussis toxin. The results show that SST2, SST3, and SST5 exhibit constitutive activity in mouse pituitary corticotroph cells, restraining adenylate cyclase and MAPK activation and ACTH secretion. SST3 mainly inhibits cAMP accumulation and ACTH secretion, whereas SST5 predominantly suppresses MAPK pathway activation. Therefore, SST receptor subtypes control pituitary cell function not only through somatostatin binding to variably expressed cell membrane receptor subtypes, but also by differential ligand-independent receptor-selective constitutive action.
Elevation of Low-Density Lipoprotein Cholesterol Concentration with Over-the-Counter Fish Oil Supplementation
Authors: Malinowski Jennifer M , Metka Kimberly
Published: July 2007

Objective:

To report a case of elevated low-density lipoprotein cholesterol (LDL-C) concentration in a patient taking fish oil supplements for hypertriglyceridemia.

Case Summary:

A 63-year-old white woman had been taking 2.7 g of eico-sapentaenotc acid (EPA) and docosahexaenoic acid (DHA) daily in 9 g of over-the-counter (OTC) fish oil capsules for triglyceride lowering. Prior to the adverse event, she had baseline fasting triglyceride (TG) and LDL-C concentrations of 278 mg/dL and 106 mg/dL, respectively. After 6 weeks of treatment with fish oil, fasting TG levels decreased by 47.5% (-132 mg/dL) and the LDL-C increased by 75% (+80 mg/dL). Discontinuation of therapy for 6 weeks resulted in TG returning to high concentrations (334 mg/dL; +56 mg/dL change from baseline) and LDL-C decreasing toward baseline (143 mg/dL; +37 mg/dL change from baseline).

Discussion:

Fish oil, an omega-3 polyunsaturated fatty acid, consists of EPA and DHA. EPA and DHA are thought to inhibit the synthesis of triglycerides in the liver. Type IV dyslipidemic patients may develop increased LDL-C levels while taking fish oil to lower triglycerides due to possible down-regulation of the LDL-C receptor in hepatic cells and formation of larger LDL particles. Use of the Naranjo probability scale indicates a probable relationship between elevations in LDL-C from baseline and initiation of fish oil treatment for hypertriglyceridemia. It is unknown whether any component within this particular product could have contributed to such an unusual elevation in LDL-C.

Conclusions:

This case documents a much higher LDL-C elevation associated with OTC fish oil supplementation than has been previously identified in the literature. Healthcare providers should be advised that LDL-C levels may increase with use of OTC fish oil and should monitor patients periodically for such elevations. The significance of this Increase on clinical outcomes is not known.
Antidepressant-lnduced Liver Injury
Authors: DeSanty Kevin P , Amabile Celene M
Published: July 2007

Objective:

To review principles of drug-induced liver injury (DILI), summarize characteristics of antidepressant-mediated liver Injury, and provide recommendations for monitoring and management.

Data Sources:

A search relating to antidepressant-induced liver injury was performed using MEDLINE (1966–March 2007). Search terms included antidepressant, cholestasis, hepatotoxicity, jaundice, liver injury, toxic hepatitis, and transaminases. Reference citations not Identified in the initial database search were also utilized.

Study Selection and Data Extraction:

All English-language case reports, letters, and review articles identified from the data sources were used. Case reports and letters relating to hepatotoxicity from antidepressant overdose were excluded.

Data Synthesis:

Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin–norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxiciiy. The tricyclic antidepressants and monoamine oxidase Inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease.

Conclusions:

Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.
Rabeprazole and Psychiatric Symptoms
Authors: Polimeni Giovanni , Cutroneo Paola , Gallo Adele , Gallo Salvatore , Spina Edoardo , Caputi Achille P
Published: July 2007

Objective:

To report the case of a patient who developed marked anxiety associated with episodes of panic attacks after starting rabeprazole therapy.

Case Summary:

An otherwise healthy 55-year-old woman was prescribed rabeprazole 20 mg/day administered in the morning tor persistent symptoms of dyspepsia. Ten days later, she presented with a 7 day history of marked anxiety associated with panic attacks, night terror (pavor nocturnus), episodic mental confusion, and attention deficit. Within 2 days of discontinuing rabeprazole, the patient recovered completely from the neuropsychiatric manifestations. Subsequent esomeprazole therapy did not cause psychiatric symptoms.

Discussion:

Rabeprazole-induced hypergastrinemia may have played a role in this neuropsychiatric adverse reaction. Several lines of evidence have indicated that gastrin-releasing peptide, whose release is mediated by proton pump inhibitor (PPI)–induced secretion of gastrin, is involved in regulating aspects of behavior that might be altered in disorders such as anxiety, depression, and dementia. The fact that rabeprazole has the highest capacity of inducing gastrin increase compared with other PPIs might explain why our patient's panic symptoms disappeared after switching to esomeprazole. Based on the Naranjo probability scale, rabeprazole was the probable cause of the adverse reaction.

Conclusions:

Specific studies are needed to investigate the potential role of PPI-induced hypergastrinemia in neuropsychiatrie adverse reactions.
Collapsing Self/Other positions: Identification through differentiation
Authors: Gillespie Alex
Published: July 2007

There is a widely recognized tendency for people to positively differentiate Self from Other. The present paper asks: What counter dynamic constrains this othering tendency? A phenomenon, termed identification through differentiation is presented in which the positive differentiation of Self from Other collapses in a moment of identification. This phenomenon is demonstrated and explored using quasi‐naturalistic group discussions with tourists in India. Three excerpts are analysed. The first demonstrates a tourist's attempt to positively differentiate him from other tourists. The second demonstrates how such an effort can collapse in a moment of identification with the previously derogated ‘other’ tourists. The third is used to explore how issues of self‐presentation complicate identification through differentiation. The discussion uses concepts from Mead (1934) and Ichheiser (1949) in order to theorize about the preconditions, interactional mechanisms and wider applicability of the phenomenon.
Binaural Helmet: Improving Speech Recognition in Noise with Spatialized Sound
Authors: Abouchacra Kim S. , Breitenbach Jean , Mermagen Timothy , Letowski Tomasz
Published: July 2007

This study assessed the effects of spatialized sound presentation on a listener's ability to monitor target (T) messages in the presence of competing (C) messages and high-level (110 dB[A]) background noise (BGN). In a simulated military environment, 8 participants wore two-channel, active noise reduction (ANR) equipped helmets and listened to combinations of T and C messages (89 dB[A] at the ear). T messages were presented synchronously with 0, 1, 2, and 3 C messages in four listening modes: (a) BGN + diotic, (b) BGN + dichotic, (c) BGN + spatial audio, and (d) quiet + spatial audio. Best overall performance occurred in the spatialized modes (c and d) and poorest in the diotic mode (a). As expected, speech recognition was better in quiet than in BGN when multiple C messages were present. Findings indicate that message spatialization in acoustic space improves auditory performance during times of heavy message competition, even in high-level noise. The proposed technology has numerous applications, such as multichannel communications in tactical operations centers, monitoring of complex security systems, and air traffic control.
Context-Dependent Memory under Stressful Conditions: The Case of Skydiving
Authors: Thompson Laura A. , Williams Keith L. , L'Esperance Paul R.
Published: July 2007

Two experiments examined the effect of differing levels of emotional arousal on learning and memory for words in matching and mismatching contexts. In Experiment 1, experienced skydivers learned words either in the air or on the ground and recalled them in the same context or in the other context. Experiment 2 replicated the stimuli and design of the first experiment except that participants were shown a skydiving video in lieu of skydiving. Recall was poor in air-learning conditions with actual skydiving, but when lists were learned on land, recall was higher in the matching context than in the mismatching context. In the skydiving video experiment, recall was higher in matching learn-recall contexts regardless of the situation in which learning occurred. We propose that under extremely emotionally arousing circumstances, environmental and/or mood cues are unlikely to become encoded or linked to newly acquired information and thus cannot serve as cues to retrieval. Results can be applied to understanding variations in context-dependent memory in occupations (e.g., police, military special operations, and Special Weapons and Tactics teams) in which the worker experiences considerable emotional stress while learning or recalling new information.
Team Training in the Skies: Does Crew Resource Management (CRM) Training Work?
Authors: Salas Eduardo , Burke C. Shawn , Bowers Clint A. , Wilson Katherine A.
Published: July 2007

The aviation community has invested great amounts of money and effort into crew resource management (CRM) training. Using D. L. Kirkpatrick's (1976) framework for evaluating training, we reviewed 58 published accounts of CRM training to determine its effectiveness within aviation. Results indicated that CRM training generally produced positive reactions, enhanced learning, and promoted desired behavioral changes. However, we cannot ascertain whether CRM has an effect on an organization's bottom line (i.e., safety). We discuss the state of the literature with regard to evaluation of CRM training programs and, as a result, call for the need to conduct systematic, multilevel evaluation efforts that will show the true effectiveness of CRM training. As many evaluations do not collect data across levels (as suggested by D. L. Kirkpatrick, 1976, and by G. M. Alliger, S. I. Tannenbaum, W. Bennett, Jr., & H. Traver, 1997), the impact of CRM cannot be truly determined; thus more and better evaluations are needed and should be demanded.
Activation of Astrocytes by CNTF Induces Metabolic Plasticity and Increases Resistance to Metabolic Insults
Authors: Escartin Carole , Pierre Karin , Colin Angélique , Brouillet Emmanuel , Delzescaux Thierry , Guillermier Martine , Dhenain Marc , Déglon Nicole , Hantraye Philippe , Pellerin Luc , Bonvento Gilles
Published: July 2007

High energy demands of neurons make them vulnerable to adverse effects of energy impairment. Recently, astrocytes were shown to regulate the flux of energy substrates to neurons. In pathological situations, astrocytes are activated but the consequences on brain energy metabolism are still poorly characterized. We found that local lentiviral-mediated gene transfer of ciliary neurotrophic factor (CNTF), a cytokine known to activate astrocytes, induced a stable decrease in the glycolytic flux in the rat striatumin vivoas measured by 2-[18F]-2-deoxy-d-glucose autoradiography and micro-positron emission tomography imaging. The activity of the mitochondrial complex IV enzyme cytochrome oxidase was not modified, suggesting maintenance of downstream oxidative steps of energy production. CNTF significantly increased the phosphorylation level of the intracellular energy sensor AMP-activated protein kinase (AMPK), supporting a specific reorganization of brain energy pathways. Indeed, we found that different key enzymes/transporters of fatty acids β-oxidation and ketolysis were overexpressed by CNTF-activated astrocytes within the striatum. In primary striatal neuron/astrocyte mixed cultures exposed to CNTF, the AMPK pathway was also activated, and the rate of oxidation of fatty acids and ketone bodies was significantly enhanced. This metabolic plasticity conferred partial glial and neuronal protection against prolonged palmitate exposure and glycolysis inhibition. We conclude that CNTF-activated astrocytes may have a strong protective potential to face severe metabolic insults.
SPARC from Olfactory Ensheathing Cells Stimulates Schwann Cells to Promote Neurite Outgrowth and Enhances Spinal Cord Repair
Authors: Au Edmund , Richter Miranda W. , Vincent Adele J. , Tetzlaff Wolfram , Aebersold Ruedi , Sage E. Helene , Roskams A. Jane
Published: July 2007

Olfactory ensheathing cells (OECs) transplanted into the lesioned CNS can stimulate reportedly different degrees of regeneration, remyelination, and functional recovery, but little is known about the mechanisms OECs may use to stimulate endogenous repair. Here, we used a functional proteomic approach, isotope-coded affinity tagging and mass spectrometry, to identify active components of the OEC secreteome that differentially stimulate outgrowth. SPARC (secreted protein acidic rich in cysteine) (osteonectin) was identified as an OEC-derived matricellular protein that can indirectly enhance the ability of Schwann cells to stimulate dorsal root ganglion outgrowthin vitro. SPARC stimulates Schwann cell-mediated outgrowth by cooperative signal with laminin-1 and transforming growth factor β. Furthermore, when SPARC-null OECs were transplanted into lesioned rat spinal cord, the absence of OEC-secreted SPARC results in an attenuation of outgrowth of specific subsets of sensory and supraspinal axons and changes the pattern of macrophage infiltration in response to the transplanted cells. These data provide the first evidence for a role for SPARC in modulating different aspects of CNS repair and indicate that SPARC can change the activation state of endogenous Schwann cells, resulting in the promotion of outgrowthin vitro, andin vivo.
Syntabulin–Kinesin-1 Family Member 5B-Mediated Axonal Transport Contributes to Activity-Dependent Presynaptic Assembly
Authors: Cai Qian , Pan Ping-Yue , Sheng Zu-Hang
Published: July 2007

The mechanism by which microtubule-based axonal transport regulates activity-dependent presynaptic plasticity in developing neurons remains mostly unknown. Our previous studies established that syntabulin is an adaptor capable of conjoining the kinesin family member 5B (KIF5B) motor and syntaxin-1. We now report that the complex of syntaxin-1–syntabulin–KIF5B mediates axonal transport of the active zone (AZ) components essential for presynaptic assembly. Syntabulin associates with AZ precursor carriers and colocalizes and comigrates with green fluorescent protein (GFP)-Bassoon-labeled AZ transport cargos within developing axons. Knock-down of syntabulin or disruption of the syntaxin-1–syntabulin–KIF5B complex impairs the anterograde transport of GFP-Bassoon out of the soma and reduces the axonal densities of synaptic vesicle (SV) clusters and FM4-64 [N-(3-triethylammoniumpropyl)-4-(p-dibutylaminostyryl)pyridinium, dibromide] loading. Furthermore, syntabulin loss of function results in a reduction in both the amplitude of postsynaptic currents and the frequency of asynchronous quantal events, and abolishes the activity-induced recruitment of new GFP-Bassoon into the axons and subsequent coclustering with SVs. Consequently, syntabulin loss of function blocks the formation of new presynaptic boutons during activity-dependent synaptic plasticity in developing neurons. These studies establish that a kinesin motor–adaptor complex is critical for the anterograde axonal transport of AZ components, thus contributing to activity-dependent presynaptic assembly during neuronal development.
Glucagon-Like Peptide 1 Stimulates Hypothalamic Proopiomelanocortin Neurons
Authors: Ma Xiaosong , Bruning Jens , Ashcroft Frances M.
Published: July 2007

Glucagon-like peptide 1 (GLP-1) is a potent inhibitor of food intake. GLP-1 receptor mRNA is densely expressed in hypothalamic arcuate nucleus (ARC) and precisely overlaps the area occupied by proopiomelanocortin (POMC) neurons. Activation of POMC neurons suppresses appetite, and lack of POMC-derived peptides or inhibition of POMC neuronal firing causes obesity. Here, we identify living POMC cells in mouse ARC brain slices by targeted expression of green fluorescent protein. Using whole-cell patch-clamp recordings, we show that GLP-1 increases the spontaneous action-potential firing of POMC neurons. The stimulatory effect of GLP-1 was mimicked by GLP-1 receptor agonist exendin-4 and abolished by the receptor antagonist exendin 9-39. The effect of GLP-1 was unchanged in the presence of the synaptic blockers DAP5 (d(-)-2-amino-5-phosphonopentanoic acid)/CNQX (6-cyano-7-nitroquinoxaline-2,3-dione disodium salt) and picrotoxin. These results suggest that GLP-1 excites POMC neurons postsynaptically, via interaction with GLP-1 receptors on POMC cells. Whole-cell Ca2+currents increased ∼70% in the presence of GLP-1, and this effect was abolished by L-type Ca2+channel antagonist nifedipine. Forskolin (which activates cAMP) mimicked the effects of GLP-1 and the PKA inhibitor Rp-8-Bromo-cAMPS (8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer) blocked GLP-1 action. These data indicate that GLP-1 stimulates the electrical activity of hypothalamic POMC neurons by activation of PKA and a subsequent increase in L-type Ca2+current. This effect may contribute to the anorectic action of GLP-1, because excitation of POMC cells is well established to reduce food intake.