bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice
Authors: van der Sluis Ronald J , Nahon Joya E , Reuwer Anne Q , Van Eck Miranda , Hoekstra Menno 
Published: January 2015

Background and PurposeAntipsychotic drugs have been shown to modulate the expression of ATP‐binding cassette transporter A1 (ABCA1), a key factor in the anti‐atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo.Experimental ApproachThioglycollate‐elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low‐density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol‐containing pellet and subsequently fed a Western‐type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo.Key ResultsHaloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP‐1 expression (−70%) and secretion (−28%) by peritoneal macrophages.Conclusions and ImplicationsHaloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis.
Relief learning is dependent on NMDA receptor activation in the nucleus accumbens
Authors: Mohammadi Milad , Fendt Markus 
Published: January 2015

Background and PurposeRecently, we demonstrated that the nucleus accumbens (NAC) is required for the acquisition and expression of relief memory. The purpose of this study was to investigate the role of NMDA receptors within the NAC in relief learning.Experimental ApproachThe NMDA receptor antagonist 2‐amino‐5‐phosphonopentanoic acid (AP‐5) was injected into the NAC. The effects of these injections on the acquisition and expression of relief memory, as well as on the reactivity to aversive electric stimuli, were tested.Key ResultsIntra‐accumbal AP‐5 injections blocked the acquisition but not the expression of relief memory. Furthermore, reactivity to aversive electric stimuli was not affected by the AP‐5 injections.Conclusion and ImplicationThe present data indicate that NMDA‐dependent plasticity within the NAC is crucial for the acquisition of relief memory.
NVP‐QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia
Authors: Coote K J , Paisley D , Czarnecki S , Tweed M , Watson H , Young A , Sugar R , Vyas M , Smith N J , Baettig U , Groot‐Kormelink P J , Gosling M , Lock R , Ethell B , Williams G , Schumacher A , Harris J , Abraham W M , Sabater J , Poll C T , Faller T , Collingwood S P , Danahay H 
Published: January 2015

Background and PurposeInhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism‐based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP‐QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia.Experimental ApproachThe in vitro potency and duration of action of NVP‐QBE170 were compared with amiloride and a newer ENaC blocker, P552‐02, in primary human bronchial epithelial cells (HBECs) by short‐circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC).Key ResultsIn vitro, NVP‐QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP‐QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP‐QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action.Conclusions and ImplicationsNVP‐QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds.
The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice
Authors: Malik Maninder , Rangel‐Barajas Claudia , Sumien Nathalie , Su Chang , Singh Meharvan , Chen Zhenglan , Huang Ren‐Qi , Meunier Johann , Maurice Tangui , Mach Robert H , Luedtke Robert R 
Published: January 2015

Background and PurposeCognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory.Experimental ApproachScopolamine‐induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg−1) were used to evaluate the ability of LS‐1–137, a novel sigma (σ1) receptor‐selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration.Key ResultsLS‐1–137 is a high‐affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80‐fold selective for σ1, compared with σ2 receptors. LS‐1–137 binds with low affinity at D2‐like (D2, D3 and D4) dopamine and muscarinic receptors. LS‐1–137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS‐1–137 treatment was also found to trigger the release of brain‐derived neurotrophic factor from rat astrocytes.Conclusions and ImplicationsThe σ1 receptor‐selective compound LS‐1–137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor‐dependent cognitive deficits.
Schizandrin ameliorates ovariectomy‐induced memory impairment, potentiates neurotransmission and exhibits antioxidant properties
Authors: Jiang Zhong‐Jiao , Wang Chun‐Yang , Xie Xun , Yang Jing‐Fang , Huang Jun‐Ni , Cao Zhi‐Ping , Xiao Peng , Li Chu‐Hua 
Published: January 2015

Background and PurposeSchizandrin (SCH) has been reported to prevent or reduce learning and memory defects. However, it is not known whether SCH ameliorates cognitive impairments induced by oestrogen deficiency. In the present study, we investigated the effect of SCH on memory in ovariectomized (OVX) and non‐OVX rats.Experimental ApproachA passive avoidance test was used to evaluate the effect of SCH on memory. Field EPSPs were recorded in hippocampal slices using an electrophysiological method. In OVX rats, biochemical parameters in the bilateral hippocampus were measured; these included superoxide dismutase (SOD), malondialdehyde (MDA) and AChE. Also, the number of NADPH‐diaphorase (NADPH‐d) positive neurons was counted by NADPH‐d histochemistry staining technique.Key ResultsOral SCH improved the memory and facilitated the induction of long‐term potentiation in non‐OVX and OVX rats; this effect was more obvious in OVX rats. Similarly, SCH perfusion enhanced synaptic transmission in hippocampal slices from both non‐OVX and OVX rats. However, SCH perfusion reduced the ratio of paired‐pulse facilitation only in OVX but not in non‐OVX rats. In addition, SCH decreased AChE activity and MDA level and increased SOD activity and the number of NADPH‐d‐positive neurons in OVX rats.Conclusions and ImplicationsSCH improves memory in OVX rats and its potential mechanisms may include a reduction in the loss of hippocampal NADPH‐d positive neurons, an increase of antioxidant properties and a potentiation of synaptic transmission that possibly involves to enhance cholinergic function. Overall, our findings indicate that SCH has potential as a therapeutic strategy for the cognitive dysfunctions associated with the menopause.
Ethnic Differences in Associations Among Popularity, Likability, and Trajectories of Adolescents' Alcohol Use and Frequency
Authors: Choukas‐Bradley Sophia , Giletta Matteo , Neblett Enrique W. , Prinstein Mitchell J. 
Published: January 2015

Two‐part latent growth models examined associations between two forms of peer status (popularity, likability) and adolescents' alcohol use trajectories throughout high school; ethnicity was examined as a moderator. Ninth‐grade low‐income adolescents (N = 364; Mage = 15.08; 52.5% Caucasian; 25.8% African American; 21.7% Latino) completed sociometric nominations of peer status and aggression at baseline, and reported their alcohol use every 6 months. After controlling for gender, aggression, ethnicity, and socioeconomic status, popularity—but not likability—prospectively predicted alcohol use trajectories. However, these effects were moderated by ethnicity, suggesting popularity as a risk factor for alcohol use probability and frequency among Caucasian and Latino, but not African American adolescents. Results suggest that developmental correlates of peer status should be considered within cultural context.
Urinary glucocorticoid metabolites: biomarkers to classify adrenal incidentalomas?
Authors: Brossaud Julie , Ducint Dominique , Corcuff Jean‐Benoît 
Published: January 2015

SummaryObjectiveTotal urinary cortisol metabolites represent cortisol production and metabolism. We hypothesized that to assay metabolites could add some information to the one provided by a sole cortisol assay.Design and patientsWe set up an inexpensive multiplex mass spectrometry assay to quantify cortisol metabolites. We investigated 43 patients with benign secreting (AT+) or silent (AT−) adrenal tumours compared to 48 lean (Nl) or 143 obese (Ob) subjects, and to 26 patients with a Cushing's disease (CD). The initial investigation included immunoreactive quantification of urinary free cortisol (UFC).ResultsCortisol metabolites were overexcreted in CD but not in Ob subjects. Nl and Ob were thus pooled in a control population (Ctl). Cortisol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE) excretions were significantly increased in AT compared to Ctl subjects, whereas immunoreactive UFC was similar. A logistic regression retaining cortisol, THF, and α‐ and β‐cortolone as significant analytes allowed the construction of a receiver‐operating characteristics (ROC) curve significantly better than the curve generated by cortisol alone (area under the curve (AUC) 0·927 vs 0·729, respectively; P < 0·0001). More importantly, although there was no significant difference between Ctl vs AT− subjects for cortisol metabolites, a logistic regression retaining cortisol, allo‐THF, and α‐ and β‐cortolone as significant analytes generated a ROC curve performing significantly better than cortisol alone (AUC 0·910 vs 0·635, respectively; P < 0·0001).ConclusionCortisol metabolite excretion is modified in AT, including AT−, patients even without modification of UFC. Clinical usefulness of these biomarkers has to be investigated in prospective studies following up patients with AT.
How many marmoset (Primates: Cebidae: Callitrichinae) genera are there? A phylogenetic analysis based on multiple morphological systems
Authors: Garbino Guilherme S. T. 
Published: January 2015

AbstractThe marmosets, tribe Callitrichini, are the most speciose clade in the subfamily Callitrichinae, containing 21 species. However, there is no consensus among molecular and morphological systematists as to how many genera should be recognized for the group. To test the morphological support for the alternative generic classifications, this study presents a comprehensive phylogenetic analysis. It is the first such analysis to include all 21 species and employ continuous and discrete osteological, pelage and tegument, karyological and vocal characters. This dataset was combined with nucleotide sequences from two mitochondrial and four nuclear regions. Separate analyses showed that, among morphological datasets, osteological characters were best at solving relationships at more inclusive levels, whilst pelage characters were most informative at the interspecific level. This suggests the presence of different transformation rates for the two character sets. When a single most parsimonious tree was obtained using the 83‐character matrix, three main clades were identified, supporting the division of the marmosets into three genera:Callithrix,CebuellaandMico. The total evidence analysis that included an additional 3481 molecular characters corroborated most of the morphology‐based clades and also supported a three‐genus classification of the marmosets. This is the first morphological study to support an Amazonian marmoset clade (Cebuella + Mico), which is also strongly supported in exclusively molecular phylogenies, and to synonimizeCallibellaunderMico.
Conservation Traps and Long‐Term Species Persistence in Human‐Dominated Systems
Authors: Cardador Laura , Brotons Lluís , Mougeot François , Giralt David , Bota Gerard , Pomarol Manel , Arroyo Beatriz 
Published: January 2015

AbstractMajor conservation efforts in human‐dominated systems, such as farmland, have focused on the establishment of subsidies and compensation promoting low‐impact management practices to reverse the impacts of conservation threats in the short term (reactive approaches). In this study, we discuss how a different way of framing conservation policy (proactive approaches) could lead to fundamentally different long‐term conservation outcomes. We define proactive approaches as those not necessarily including measures directly addressing the threats affecting biodiversity, but promoting transitions from current scenarios in which species are threatened to new states in which the threat is no longer present. We illustrate reactive and proactive approaches using as a case study two contrasting conservation frameworks for a vulnerable farmland bird, the Montagu's harrier (Circus pygargus) in northeastern Spain. This example shows that reactive approaches can lead to “conservation traps,” which we defined as situations where the application of biologically focused actions in response to conservation problems results in an unsustainable need to perpetuate the implementation of those actions. Our aim is to offer a fresh perspective on biodiversity conservation in human‐dominated systems and to stimulate alternative, more holistic approaches in conservation promoting transitions to new states not requiring long‐term active and costly conservation action.
Concerns of ABO incompatible and crossmatch‐positive potential donors and recipients about participating in kidney exchanges
Authors: Rodrigue James R. , Leishman Ruthanne , Vishnevsky Tanya , Evenson Amy , Mandelbrot Didier A. 
Published: January 2015

AbstractKidney paired exchanges (KPEs) have increased, yet are still underutilized. This study aimed to develop tools for assessing KPE concerns, identify predictors of KPE concerns, and describe common KPE concerns among potential living donors (LDs) and intended recipients. Incompatible former potential LDs (n = 135) and intended recipients (n = 83) retrospectively completed questionnaires to assess KPE concerns. Healthcare system distrust also was assessed. A minority (n = 48 or 36.5% of potential LDs; n = 25 or 30.1% of intended recipients) had pursued KPE participation. Of those who pursued KPE participation, 11 (22.9%) and 6 (24.0%) completed KPE donation or transplantation, respectively. The questionnaires for potential LDs and recipients showed good internal consistency and preliminary convergent validity. LDs and patients less willing to pursue KPE reported more KPE concerns. Common KPE concerns for both potential LDs and recipients were related to perceived Distrust/Inequity and Inconvenience/Cost. Multivariate predictors of more KPE concerns were as follows: male gender (t = 4.5, p < 0.001) and more healthcare system distrust (t = 2.5, p = 0.01) for potential LDs; black race (t = 2.1, p = 0.04) and more healthcare system distrust (t = 2.3, p = 0.03) for intended recipients. These findings underscore the importance of addressing concerns potential LDs and patients have about KPE if the true potential of KPE is to be realized.
Multivariable risk of developing new onset diabetes after transplant—results from a single‐center study of 481 adult, primary kidney transplant recipients
Authors: Gaynor Jeffrey J. , Ciancio Gaetano , Guerra Giselle , Sageshima Junichiro , Hanson Lois , Roth David , Goldstein Michael J. , Chen Linda , Kupin Warren , Mattiazzi Adela , Tueros Lissett , Flores Sandra , Barba Luis J. , Lopez Adrian , Rivas Jose , Ruiz Phillip , Vianna Rodrigo , Burke George W. 
Published: January 2015

AbstractBackgroundUnderstanding the relative contributions of baseline demographics and immunosuppressive therapy on NODAT risk may help in developing preventive strategies.MethodsUsing our prospectively followed cohort of 481 adult, primary kidney transplant recipients without pre‐transplant diabetes, we determined the significant baseline predictors for the hazard rate of developing NODAT via Cox stepwise regression. The multivariable influence of first BPAR (defined as a time‐dependent covariate) was also tested.ResultsMedian follow‐up was 57 mo post‐transplant; the overall percentage who developed NODAT was 22.5% (108/481). Four baseline predictors of a greater NODAT hazard rate were found (by order of selection): higher BMI (p < 0.000001), planned maintenance with SRL (p = 0.0003), non‐white recipient (p = 0.0004), and older recipient age (p = 0.0004). Approximately one‐half of the 106 patients in the highest demographic risk category (BMI ≥25 kg/m2, non‐white race, and age at transplant ≥40 yr) developed NODAT; actuarial NODAT risk ranged from 10% to 30% in the lower demographic risk categories. First BPAR was also associated with significantly higher NODAT in multivariable analysis (p = 0.02)—the highly elevated NODAT rate observed during the first few months post‐transplant and following first BPAR appears to demonstrate the diabetogenic effect of using high‐dose (intravenous) corticosteroids.ConclusionsThe disturbingly high NODAT rate found among patients having multiple demographic risk factors is still an important problem that awaits a better solution.
Health‐related quality of life may improve after transplantation in pancreas–kidney recipients
Authors: Martins La Salete , Outerelo Cristina , Malheiro Jorge , Fonseca Isabel M. , Henriques António C. , Dias Leonídio S. , Rodrigues Anabela S. , Cabrita António M. , Noronha Irene L. 
Published: January 2015

AbstractPancreas–kidney transplantation (PKT) may significantly improve quality of life (HRQOL) in patients with type 1 diabetes. We have assessed the changes felt by PKT patients, using the Gastrointestinal Quality of Life Index (GIQLI) and EuroQol‐5D questionnaires. Patients were asked to compare how their HRQOL had changed from pre‐transplantation to the last visit. The 60 men and 66 women enrolled had a mean follow‐up of five yr; 84.1% with both grafts, 15.9% with one graft functioning. In all domains of EuroQol‐5D scores improved after PKT, as well as the visual analogue scale health state (from 38% to 84%, p < 0.001; effect size 3.34). In GIQLI, physical function was felt better after PKT than before (14.83 ± 3.86 vs. 7.86 ± 4.43, p < 0.001; effect size 1.68); the same was observed for psychological status, social function, and GI complaints. Concerning the burden of medical treatment, the score significantly improved (from 1.31 to 3.63, p < 0.001, effect size 2.02). The rate of unemployed patients decreased after PKT (from 50.8% to 36.5%, p < 0.001). Multivariate analysis showed that having only one functioning graft was associated with worse HRQOL scores (B = −5.157, p = 0.015). In conclusion, for all assessed domains, patients reported a significant improvement in HRQOL after PKT. Maintenance of the two grafts functioning predicted higher improvement of HRQOL scores.
“An Arena Where Meaning and Identity Are Debated and Contested on a Global Scale”: Narrative Discourses in British Museum Exhibitions, 1972–2013
Authors: Francis David 
Published: January 2015

AbstractFollowing the so‐called narrative turn in the social sciences, museums have increasingly been conceptualized as narrative environments (MacLeod 2012). This narrative approach is characterized by a focus on museum exhibitions as spaces that tell stories rather than as repositories of knowledge (Roberts ). Despite the ubiquity of the term “narrative” in museums, relatively few studies have attempted to use literary theory to understand how these narrative spaces function. This paper attempts to apply some of the analytical models of the Russian literary theorist Mikhail Bakhtin to museum displays in order to examine how competing internal and external discourses shape exhibition narratives. This study looks at eight British Museum exhibitions beginning with Treasures of Tutankhamun in 1972 and ending with Hajj: Journey to the Heart of Islam in 2012. It explores how Bakhtin's theoretical concepts, including the “dialogic nature of discourse,” “heteroglossia” and the “carnivalesque,” can aid our critical understanding of museum displays as discursive spaces. External discourses often enter the museum unnoticed, regardless of authorial/curatorial intent, and are often impossible to keep out. However, by being critically aware of how discourse functions, museum professionals can use the techniques of literary theory to create innovative exhibitions that promote reflection and discussion about the connections between the historical past and the world in which we live today.