bluuebunny/crossref_metadata_2025_split huggingface dataset:
The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction
Authors: Milton Amy L. , Everitt Barry J. 
Published: May 2010

AbstractMemory reconsolidation is the process by which memories, destabilised at retrieval, require restabilisation to persist in the brain. It has been demonstrated that even old, well‐established memories require reconsolidation following retrieval; therefore, memory reconsolidation could potentially be exploited to disrupt, or even erase, aberrant memories that underlie psychiatric disorders, thereby providing a novel therapeutic target. Drug addiction is one such disorder; it is both chronic and relapsing, and one prominent risk factor for a relapse episode is the presentation of environmental cues that have previously been associated with drugs of abuse. This ‘cue‐induced relapse’ can be accounted for in psychological terms by reinforcing memories of the pavlovian association between the cue and the drug, which can thus influence behaviour through at least three psychologically and neurobiologically dissociable mechanisms: conditioned reinforcement, conditioned approach and conditioned motivation. As each of these psychological processes could contribute to the resumption of drug‐seeking following abstinence, it is important to develop treatments that can reduce drug‐seeking re‐established via influences on each or all of these pavlovian processes, in order to minimise the risk of a subsequent relapse. Investigation of the memory reconsolidation mechanisms of the memories underlying conditioned reinforcement, conditioned approach and conditioned motivation indicate that they depend upon different neurochemical systems, including the glutamatergic and adrenergic systems within limbic corticostriatal circuitry. We also discuss here the subsequent translation to the clinic of this preclinical work.
Converting juvenile into adult plasticity: a role for the brain’s extracellular matrix
Authors: Gundelfinger Eckart D. , Frischknecht Renato , Choquet Daniel , Heine Martin 
Published: May 2010

AbstractIn higher vertebrates, the extracellular matrix (ECM) wrapping cells of the adult brain differs significantly from that of the developing and juvenile brain. The mature ECM is established at the end of critical periods for wiring and it restricts the regenerative potential and constrains the plasticity of the adult brain. In particular, perineuronal nets, elaborate ECM structures that surround distinct neurons and wrap synapses, are hallmarks of the adult brain and seem to massively affect brain plasticity. Why have these, at first glance futile, limitations evolved? What is the return for these drawbacks? What are the mechanisms of restriction and how is adult plasticity implemented? Recent progress both at the systemic level and at the molecular physiological level has shed some new light on these questions. In this review we will survey the evidence for potential functions of the adult ECM in making established brain features, including imprinted memories, resistant to extinction, and we will discuss potential mechanisms by which the ECM limits juvenile and implements adult plasticity. In particular we will focus on some aspects of adult ECM function. First we will discuss its influence on diffusion of cations in the extracellular space and on volume transmission, second we will consider its potential role in regulating the lateral diffusion of cell surface receptors and finally we will discuss mechanisms to locally modulate ECM functions.
TRPA1‐expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord
Authors: Uta Daisuke , Furue Hidemasa , Pickering Anthony E. , Harunor Rashid Md , Mizuguchi‐Takase Hiroko , Katafuchi Toshihiko , Imoto Keiji , Yoshimura Megumu 
Published: May 2010

AbstractThe TRPA1 channel has been proposed to be a molecular transducer of cold and inflammatory nociceptive signals. It is expressed on a subset of small primary afferent neurons both in the peripheral terminals, where it serves as a sensor, and on the central nerve endings in the dorsal horn. The substantia gelatinosa (SG) of the spinal cord is a key site for integration of noxious inputs. The SG neurons are morphologically and functionally heterogeneous and the precise synaptic circuits of the SG are poorly understood. We examined how activation of TRPA1 channels affects synaptic transmission onto SG neurons using whole‐cell patch‐clamp recordings and morphological analyses in adult rat spinal cord slices. Cinnamaldehyde (TRPA1 agonist) elicited a barrage of excitatory postsynaptic currents (EPSCs) in a subset of the SG neurons that responded to allyl isothiocyanate (less specific TRPA1 agonist) and capsaicin (TRPV1 agonist). Cinnamaldehyde evoked EPSCs in vertical and radial but not islet or central SG cells. Notably, cinnamaldehyde produced no change in inhibitory postsynaptic currents and nor did it produce direct postsynaptic effects. In the presence of tetrodotoxin, cinnamaldehyde increased the frequency but not amplitude of miniature EPSCs. Intriguingly, cinnamaldehyde had a selective inhibitory action on monosynaptic C‐ (but not Aδ‐) fiber‐evoked EPSCs. These results indicate that activation of spinal TRPA1 presynaptically facilitates miniature excitatory synaptic transmission from primary afferents onto vertical and radial cells to initiate action potentials. The presence of TRPA1 channels on the central terminals raises the possibility of bidirectional modulatory action in morphologically identified subclasses of SG neurons.
Subjective neuronal coding of reward: temporal value discounting and risk
Authors: Schultz Wolfram 
Published: May 2010

AbstractA key question in the neurobiology of reward relates to the nature of coding. Rewards are objects that are advantageous or necessary for the survival of individuals in a variety of environmental situations. Thus reward appears to depend on the individual and its environment. The question arises whether neuronal systems in humans and monkeys code reward in subjective terms, objective terms or both. The present review addresses this issue by dealing with two important reward processes, namely the individual discounting of reward value across temporal delays, and the processing of information about risky rewards that depends on individual risk attitudes. The subjective value of rewards decreases with the temporal distance to the reward. In experiments using neurophysiology and brain imaging, dopamine neurons and striatal systems discount reward value across temporal delays of a few seconds, despite unchanged objective reward value, suggesting subjective value coding. The subjective values of risky outcomes depend on the risk attitude of individual decision makers; these values decrease for risk‐avoiders and increase for risk‐seekers. The signal for risk and the signal for the value of risky reward covary with individual risk attitudes in regions of the human prefrontal cortex, suggesting subjective rather than objective coding of risk and risky value. These data demonstrate that important parameters of reward are coded in a subjective manner in key reward structures of the brain. However, these data do not rule out that other neurons or brain structures may code reward according to its objective value and risk.
Indirect predator effects on clutch size and the cost of egg production
Authors: Travers Marc , Clinchy Michael , Zanette Liana , Boonstra Rudy , Williams Tony D. 
Published: May 2010

Ecology Letters (2010) 13: 980–988AbstractPredator‐induced changes in physiology and behaviour may negatively affect a prey’s birth rate. Evidence of such indirect predator effects on prey demography remains scarce in birds and mammals despite invertebrate and aquatic studies that suggest ignoring such effects risks profoundly underestimating the total impact of predators. We report the first experimental demonstration of indirect predator effects on the annual ‘birth’ rate resulting from negative effects on the size of subsequent clutches laid by birds. We manipulated the probability of nest predation and measured the size of subsequent clutches and multiple indices of the mother’s physiological condition, while controlling for food availability, date and stage of breeding. Females subject to frequent experimental nest predation laid smaller subsequent clutches and were in poorer physiological condition, particularly regarding non‐resource‐based indices (e.g. oxidative stress and glucocorticoid mobilization) consistent with both a response to the threat of predation and an increased cost of egg production.
Patterns and ecosystem consequences of shark declines in the ocean
Authors: Ferretti Francesco , Worm Boris , Britten Gregory L. , Heithaus Michael R. , Lotze Heike K. 
Published: May 2010

Ecology Letters (2010) 13: 1055–1071AbstractWhereas many land predators disappeared before their ecological roles were studied, the decline of marine apex predators is still unfolding. Large sharks in particular have experienced rapid declines over the last decades. In this study, we review the documented changes in exploited elasmobranch communities in coastal, demersal, and pelagic habitats, and synthesize the effects of sharks on their prey and wider communities. We show that the high natural diversity and abundance of sharks is vulnerable to even light fishing pressure. The decline of large predatory sharks reduces natural mortality in a range of prey, contributing to changes in abundance, distribution, and behaviour of small elasmobranchs, marine mammals, and sea turtles that have few other predators. Through direct predation and behavioural modifications, top‐down effects of sharks have led to cascading changes in some coastal ecosystems. In demersal and pelagic communities, there is increasing evidence of mesopredator release, but cascading effects are more hypothetical. Here, fishing pressure on mesopredators may mask or even reverse some ecosystem effects. In conclusion, large sharks can exert strong top‐down forces with the potential to shape marine communities over large spatial and temporal scales. Yet more empirical evidence is needed to test the generality of these effects throughout the ocean.
Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse‐controlled release for obesity
Authors: Kang J. G. , Park C.‐Y. , Kang J. H. , Park Y.‐W. , Park S. W. 
Published: May 2010

Aim: To evaluate the efficacy and safety of a newly developed formulation of phentermine diffuse‐controlled release (DCR) in patients with obesity. Methods: This was a randomized, double‐blind, placebo‐controlled trial of 12 weeks of treatment with phentermine DCR 30 mg (n = 37) or placebo (n = 37), administered once daily in patients with obesity with controlled diabetes, hypertension or dyslipidaemia. The efficacy was evaluated by changes in body weight and waist circumference from baseline at 12 weeks and also changes in metabolic parameters, including lipid profiles and blood pressure. Results: The participants in the phentermine DCR group showed significant reductions in body weight (−8.1 ± 3.9 vs. −1.7 ± 2.9 kg, p < 0.001) and waist circumference (7.2 ± 0.5 vs. 2.1 ± 0.6 cm, p < 0.001) compared with those in the placebo group. Weight reductions of 5% or greater from the baseline (95.8 vs. 20.8%, p < 0.001) and 10% or more (62.5 vs. 4.7%, p < 0.001) were achieved in the DCR phentermine group and placebo group, respectively. Total cholesterol and low‐density lipoprotein cholesterol (LDL‐C) levels were significantly improved in the phentermine DCR group. However, there were no significant differences in systolic and diastolic blood pressure between the groups. Dry mouth and insomnia were the most common adverse events, but these were mild to moderate and transient. Conclusions: Short‐term phentermine DCR treatment resulted in significant reduction in weight and improvement of metabolic parameters, including waist circumference and some lipid profiles, without clinically severe adverse events. Further study is needed to show long‐term efficacy and safety of phentermine DCR in Korean patients with obesity.
8‐isoprostane F2αup‐regulates the expression of type 5 phosphodiesterase in cavernosal vascular smooth muscle cells: inhibition with sildenafil, iloprost, nitric oxide and picotamide
Authors: Hotston Matthew , Jeremy Jamie Y. , Persad Raj , Bloor Jonathon , Shukla Nilima 
Published: May 2010

OBJECTIVESTo explore the possible role of of 8‐isoprostane F2α(8‐IPF2α) in the aetiology of erectile dysfunction (ED), as the over‐production of superoxide (O2‐) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase results in the formation of 8‐IPF2αin vascular tissue, which has similar properties to thromboxane A2(TXA2). TXA2is vasoconstrictor and up‐regulates the expression of NADPH oxidase and phosphodiesterase type 5 (PDE5).MATERIALS AND METHODSCavernosal vascular smooth muscle cells (CVSMCs) were incubated with 8‐IPF2αor the TXA2analogue, U46619, ±sildenafil, iloprost (a stable prostacyclin [PGI2] analogue) or the nitric oxide (NO) donor NONOate for 16 h. The formation of O2‐was then measured, PDE5 expression assessed using Western blotting and PGI2and 8‐IPF2αformation measured using enzyme‐linked immunoassays.RESULTS8‐IPF2αpromoted the formation of O2‐, an effect inhibited by apocynin (an NADPH oxidase inhibitor) and up‐regulated the expression of PDE5. Under identical incubation conditions, 8‐IPF2αinduced an increase in the formation of 8‐IPF2αbut reduced the formation of PGI2. All, these effects were reversed by sildenafil, iloprost, NONOate and picotamide.CONCLUSIONSThese data show that O2‐derived from NADPH oxidase influences the relative balance of PGI2and 8‐IPF2αin CVSMCs, which in turn alters the degree of PDE5 expression. This is a novel pathogenic mechanism underlying ED and a novel mechanism of action of sildenafil.
Late morbidity and oncological outcome after radical hypofractionated radiotherapy in men with prostate cancer
Authors: Di Staso Mario , Bonfili Pierluigi , Gravina Giovanni L. , Di Genesio Pagliuca Milena , Franzese Pietro , Buonopane Sergio , Osti Mattia F. , Valeriani Maurizio , Festuccia Claudio , Enrici Riccardo Maurizi , Tombolini Vincenzo 
Published: May 2010

Study Type – Therapy (case control) Level of Evidence 3bOBJECTIVETo test the hypothesis that three‐dimensional hypofractionated radiotherapy (3D‐HFRT) is well tolerated and not worse than 3‐D conventional RT (3D‐CRT) for oncological outcome.PATIENTS AND METHODSIn all, 162 men with hystologically confirmed prostate adenocarcinoma were included in the analysis. In all, 82 men were treated with 3D‐HFRT (15 fractions of 3.62 Gy delivered 3 times/week; a total dose of 54.3 Gy). This group was retrospectively compared with 80 men who met the same inclusion criteria and who were treated with 3D‐CRT (39 fractions of 2 Gy delivered daily; a total dose of 78 Gy). A short course of hormone therapy was administered concomitantly with the RT.RESULTSOnly one (1.7%) patient in the 3D‐CRT group and two (4.0%) in the 3D‐HFRT group had Grade 3 genitourinary toxicity. There was late gastrointestinal morbidity of ≥ grade 3 in only 5.1% of men treated with 3D‐HFRT and in 4.0% of men treated with 3D‐CRT. In both groups there was no Grade 4 toxicity. At the median (range) follow‐up of 45 (39.4–51) months for the 3D‐HFRT group and 57.5 (54.9–59.1) months for 3D‐CRT group the progression rate was 18/82 (21.9%) and 20/80 (25.0%), respectively, with no significant worsening in the risk of biochemical failure (BCF; log‐rank test, P= 0.222).CONCLUSIONSIn the present study, men with clinically localized prostate cancer had similar levels of morbidity irrespective of whether they received HFRT or CRT without any worsening in the early risk of BCF. Thus, the present data provide some clinical evidence to justify trends already emerging toward HF regimens for treating clinically localised prostate cancer.
25‐year experience in the outcome of artificial urinary sphincter in the treatment of female urinary incontinence
Authors: Chung Eric , Cartmill Ross A. 
Published: May 2010

Study Type – Therapy (outcomes research) Level of Evidence 2cOBJECTIVETo report the outcome of artificial urinary sphincter (AUS) in female patients for the treatment of stress urinary incontinence (SUI).PATIENTS AND METHODSWe retrospectively reviewed all female patients with AUS implanted over the last 25 years in one institution. Patient demographics, renal tract imaging and urodynamics assessment were documented. Outcomes measures included complications, duration and cause of AUS failure. Urinary continence was defined as no pad use after AUS insertion. AUS failure was defined as malfunction, infection or erosion. AUS malfunction included either mechanical (fluid leak) or non‐mechanical (infection or surgical damage to AUS). A Kaplan–Meier analysis was used to determine device failure over time.RESULTSIn all, 47 consecutive women with a mean (range) age of 51 (17–78) years received an AUS for the treatment of UI. Of these, 35 women had failed anti‐incontinence surgery previously. There were two wound infections after AUS insertion but no mortality. Of the 47 AUS implanted, 39 (83%) AUS remained in situ. Eight (17%) AUS were removed due to AUS erosion or infection. There were 20 AUS revisions, 16 of which were primary AUS revisions. Most of the AUS revisions were related to mechanical malfunctions. Comparison of the proportion of AUS device survival over time using Kaplan–Meier analysis showed >80% of AUS remained functioning after 100 months. At the time of review, 83% of patients had a device in situ and the continence rate with no pads use was 59% with AUS only; this figure increased to 85% when concurrent clean intermittent self‐catheterization was performed.CONCLUSIONSAUS is an effective and durable treatment option for female SUI. In properly selected women, high continence rates can be achieved. Most patients maintained satisfactory long‐term continence rates despite revision surgery.
Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis
Authors: Black Peter C. , Shetty Anil , Brown Gordon A. , Esparza‐Coss Emilio , Metwalli Adam R. , Agarwal Piyush K. , McConkey David J. , Hazle John D. , Dinney Colin P.N. 
Published: May 2010

OBJECTIVETo assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy.MATERIALS AND METHODSOrthotopic bladder tumours were established in nude mice with KU7 and 253J B‐V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1‐mm step‐sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified.RESULTSThe correlation between MRI volume and BLI was weak in KU7 xenografts (R2 < 0.1) but strong in 253J B‐V (R2= 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R2= 0.42).CONCLUSIONThe correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method.
Nutritively sweetened beverage consumption and body weight: a systematic review and meta‐analysis of randomized experiments
Authors: Mattes R. D. , Shikany J. M. , Kaiser K. A. , Allison D. B. 
Published: May 2010

SummaryNutritively sweetened beverages (NSBs) may play a role in the obesity epidemic. We abstracted data from randomized controlled trials (RCTs) and evidence‐based reviews through January 2009 concerning effects of consumption of NSBs on changes in body weight and adiposity. Studies included were those (i) conducted in humans; (ii) lasting at least 3 weeks; (iii) incorporating random assignment of subjects to conditions that differed only in the consumption of NSBs and (iv) including an adiposity indicator as an outcome. Twelve studies met the inclusion criteria. Meta‐analysis of six studies that added NSBs to persons' diets showed dose‐dependent increases in weight. Contrarily, meta‐analysis of studies that attempted to reduce NSB consumption consistently showed no effect on body mass index (BMI) when all subjects were considered. Meta‐analysis of studies providing access to results separately for subjects overweight at baseline showed a significant effect of a roughly 0.35 standard deviations lesser BMI change (i.e. more weight loss or less weight gain) relative to controls. The current evidence does not demonstrate conclusively that NSB consumption has uniquely contributed to obesity or that reducing NSB consumption will reduce BMI levels in general. We recommend an adequately powered RCT with overweight persons, for whom there is suggestive evidence of an effect.
‘Every space is claimed’: smokers’ experiences of tobacco denormalisation
Authors: Bell Kirsten , McCullough Lucy , Salmon Amy , Bell Jennifer 
Published: May 2010

AbstractOver the past decade, the strategy of ‘denormalising’ tobacco use has become one of the cornerstones of the global tobacco control movement. Although tobacco denormalisation policies primarily affect people on the lowest rungs of the social ladder, few qualitative studies have explicitly set out to explore how smokers have experienced and responded to these legislative and social changes in attitudes towards tobacco use. Drawing on a qualitative study of interviews with 25 current and ex‐smokers living in Vancouver, Canada, this paper examines the ways they interpret and respond to the new socio‐political environment in which they must manage the increasingly problematised practice of tobacco smoking. Overall, while not opposed to smoking restrictions per se, study participants felt that recent legislation, particularly efforts to prohibit smoking in a variety of outdoor settings, was overly restrictive and that all public space had increasingly been ‘claimed’ by non‐smokers. Also apparent from participants’ accounts was the high degree of stigma attached to smoking. However, although the ‘denormalisation’ environment had encouraged several participants to quit smoking, the majority continued to smoke, raising ethical and practical questions about the value of denormalisation strategies as a way of reducing smoking‐related mortality and morbidity.