bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived information needs and non‐adherence: evidence from Greek patients with hypertension
Authors: Stavropoulou Charitini
Published: April 2011

Background  The role of information on patients’ decision to non‐adhere is important, yet not well explored.

Objective  To identify differences between perceived information needs for hypertension and medication to treat it, to explore the information channels used by patients and to test what type of information is more important to adhere to medication.

Design, setting and participants  A questionnaire study was designed and conducted by telephone in the Centre for the Treatment of Hypertension in Athens, Greece, among 743 individuals.

Main variables studied  The main variables included perceived information needs, information channels, non‐adherence to medication and socio‐demographic characteristics.

Main outcome measures  Non‐adherence to medication was measured using the Morisky scale.

Results  Patients reported feeling better informed about hypertension (90%) than medication to treat it (80%). The doctor remains the dominant information source, while the Media and magazines on health issues were reported more frequently than the family and the pharmacist. Feeling well informed about medication for hypertension was a predictor of better adherence. Other determinants of adherence were the use of the Internet and the Media.

Discussion  The results confirm the importance of patients leaving the consultation feeling well informed about their medication as this improves adherence. They also show that the use of the Internet and the Media can be beneficial for adherence.

Conclusions  Given the restricted time the doctor can usually spend with the patient, it is important to know that more emphasis on the information regarding medication is important.
Which anti‐platelet therapies might be beneficial in xenotransplantation?
Authors: Schmelzle Moritz , Cowan Peter J. , Robson Simon C.
Published: April 2011

Schmelzle M, Cowan PJ, Robson SC. Which anti‐platelet therapies might be beneficial in xenotransplantation? Xenotransplantation 2011; 18: 79–87. © 2011 John Wiley & Sons A/S.

Abstract:  Xenotransplantation could provide an unlimited and elective supply of grafts, once mechanisms of graft loss and vascular injury are better understood. The development of α‐1,3‐galactosyltransferase gene‐knockout (GalT‐KO) swine with the removal of a dominant xeno‐antigen has been an important advance; however, delayed xenograft and acute vascular reaction in GalT‐KO animals persist. These occur, at least in part, because of humoral reactions that result in vascular injury. Intrinsic molecular incompatibilities in the regulation of blood clotting and extracellular nucleotide homeostasis between discordant species may also predispose to thrombophilia within the vasculature of xenografts. Although limited benefits have been achieved with currently available pharmacological anti‐thrombotics and anti‐coagulants, the highly complex mechanisms of platelet activation and thrombosis in xenograft rejection also require potent immunosuppressive interventions. We will focus on recent thromboregulatory approaches while elucidating appropriate anti‐platelet mechanisms. We will discuss potential benefits of additional anti‐thrombotic interventions that are possible in transgenic swine and review recent developments in pharmacological anti‐platelet therapy.
Xenotransplantation literature update, January–February 2011
Authors: Schneider Mårten K. J. , Seebach Jörg D.
Published: April 2011

Schneider MKJ, Seebach JD. Xenotransplantation literature update, January–February 2011. Xenotransplantation 2011; 18: 147–150. © 2011 John Wiley & Sons A/S.
Versatile co‐expression of graft‐protective proteins using 2A‐linked cassettes
Authors: Fisicaro Nella , Londrigan Sarah L. , Brady Jamie L. , Salvaris Evelyn , Nottle Mark B. , O’Connell Philip J. , Robson Simon C. , d’Apice Anthony J. F. , Lew Andrew M. , Cowan Peter J.
Published: April 2011

Fisicaro N, Londrigan SL, Brady JL, Salvaris E, Nottle MB, O’Connell PJ, Robson SC, d’Apice AJF, Lew AM, Cowan PJ. Versatile co‐expression of graft‐protective proteins using 2A‐linked cassettes. Xenotransplantation 2011; 18: 121–130. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  Expression of multiple graft‐protective proteins targeted to different locations (i.e., intracellular, cell surface, and secreted) has become an increasingly important goal in xenotransplantation. The 2A “ribosome skip” signal is used as a linker to enable transgene co‐expression, but some studies have shown that post‐translational modification and trafficking of 2A‐linked proteins may be adversely affected depending on their position relative to 2A. We tested whether several relevant proteins, subject to a range of processing and localization mechanisms, could be efficiently co‐expressed using the 2A system.

Methods:  Six expression cassettes were constructed, each containing up to four 2A‐linked open reading frames, encoding combinations of human CD55, thrombomodulin (TBM), CD39, CTLA4‐Ig and hygromycin resistance. Each linker incorporated a furin cleavage site to remove the carboxy‐terminal extension that remains on upstream proteins after 2A processing. The cassettes were used to produce vectors for transfection, adenoviral transduction and transgenesis. Expression was detected by flow cytometry and/or Western blotting.

Results:  All proteins were expressed in the appropriate location following transient transfection of COS‐7 cells, irrespective of the number of linked genes. The percentage of stable transfectants expressing a linked gene was increased 10‐fold (from 4–5% to 58–67%) by incorporating the hygromycin resistance gene into the cassette. Stable transfection of transgenic GalT KO pig fibroblasts with a hygromycin‐ TBM‐CD39 construct resulted in surface expression of both TBM and CD39 by the majority of hygromycin‐resistant cells. Expression was maintained after flow cytometric sorting and expansion. Adenoviral transduction of NIT‐1 mouse insulinoma cells with a TBM‐CD39 construct resulted in strong expression of both genes on the cell surface. Mice transgenic for 3‐gene (CD55‐ TBM‐CD39) or 4‐gene (CD55‐ TBM‐CTLA4Ig‐CD39) constructs expressed all genes except CD55.

Conclusions:  These results confirm the versatility of the 2A system, and demonstrate that careful construct design can minimize potential problems with post‐translational modification and trafficking. In addition, incorporation of a selection marker into the 2A‐linked chain can dramatically increase the proportion of stable transfectants expressing proteins of interest. This provides a powerful method for the rapid modification of existing genetically modified pigs.
Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection
Authors: Nguyen Bao‐Ngoc H. , Azimzadeh Agnes M. , Schroeder Carsten , Buddensick Thomas , Zhang Tianshu , Laaris Amal , Cochrane Megan , Schuurman Henk‐Jan , Sachs David H. , Allan James S. , Pierson III Richard N.
Published: April 2011

Nguyen B‐NH, Azimzadeh AM, Schroeder C, Buddensick T, Zhang T, Laaris A, Cochrane M, Schuurman H‐J, Sachs DH, Allan JS, Pierson RN. Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection. Xenotransplantation 2011; 18: 94–107. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  Galactosyl transferase gene knock‐out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection.

Methods:  We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild‐type and human decay‐accelerating factor‐transgenic (hDAF+/+) pig lungs.

Results:  GalTKO lungs survived 132 ± 52 min compared to 10 ± 9 min for wild‐type lungs (P = 0.001) and 45 ± 60 min for hDAF+/+ lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild‐type or hDAF+/+ lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild‐type or hDAF+/+ lungs. However, GalTKO lungs adsorbed cytotoxic anti‐non‐Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points.

Conclusions:  In summary, GalTKO lungs are substantially protected from injury but, in addition to anti‐non‐Gal antibody and complement, platelet adhesion and non‐physiologic intravascular coagulation contribute to Gal‐independent lung injury mechanisms.
Identification of soluble and membrane‐bound isoforms of porcine tumor necrosis factor receptor 2
Authors: Uribe‐Herranz Mireia , Casinghino Sandra R. , Bosch‐Presegué Laia , Fodor William L. , Costa Cristina
Published: April 2011

Uribe‐Herranz M, Casinghino SR, Bosch‐Presegué L, Fodor WL, Costa C. Identification of soluble and membrane‐bound isoforms of porcine tumor necrosis factor receptor 2. Xenotransplantation 2011; 18: 131–146. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  TNF and its receptors TNF‐Receptor 1 (TNFR1, CD120a) and TNF‐Receptor 2 (TNFR2, CD120b) have been implicated in the rejection of transplanted cells and organs. Although pig TNFR1 (pTNFR1) is known to mediate the effects of human TNF in a xenogeneic setting, it is unclear whether pig TNFR2 (pTNFR2) could contribute to xenograft rejection.

Methods:  We have cloned the cDNA of various pTNFR2 variants by reverse transcription–polymerase chain reaction (RT‐PCR) and rapid amplification of cDNA ends. We have characterized the predicted proteins with bioinformatic tools and conducted expression, affinity, and functional studies to investigate their roles.

Results:  We have identified four isoforms of pTNFR2: one comprising the four cysteine‐rich domains (CRD) conserved between species, a shorter variant (pTNFR2ΔE7‐10) encoding for a soluble isoform, another with only three CRD due to the lack of exon 4 (pTNFR2ΔE4), and a fourth variant containing both modifications. Accordingly, multiple mRNA transcripts were observed by northern blotting. Quantitative RT‐PCR determined high pTNFR2 expression in lung and immune cells and detected the two alternative splicings in all cells/tissues examined. The full receptor was moderately expressed on the surface of pig cells such as porcine aortic endothelial cells and PK‐15 and was regulated by TNF. On the contrary, the membrane‐bound pTNFR2ΔE4 was located only intracellularly. Plasmon resonance studies showed that pTNFR2 binds pig and human TNFα with high affinity, but pTNFR2ΔE4 interacts poorly with pig TNFα and does not bind to the human cytokine. Moreover, pull‐down experiments with the two recombinant soluble isoforms consistently demonstrated that the two bound together and soluble pTNFR2ΔE4 was able to modulate the TNF inhibitory activity of pTNFR2‐GST in a cell‐based assay.

Conclusion:  The pTNFR2 may participate in the process of xenograft rejection and other related events, as well as be used in soluble form to block TNF in this setting. In addition, we have discovered other pTNFR2 isoforms that may affect the pig immune responses and have an impact on rejection of xenografts.
Plastidic isoprenoid biosynthesis in tomato: physiological and molecular analysis in genotypes resistant and sensitive to drought stress
Authors: Loyola J. , Verdugo I. , González E. , Casaretto J. A. , Ruiz‐Lara S.
Published: April 2011

Isoprenoid compounds synthesised in the plastids are involved in plant response to water deficit. The functionality of the biosynthetic pathway of these compounds under drought stress has been analysed at the physiological and molecular levels in two related species of tomato (Solanum chilense and Solanum lycopersicum) that differ in their tolerance to abiotic challenge. Expression analysis of the genes encoding enzymes of these pathways (DXS, IPI, GGPPS, PSY1, NCED and HPT1) in plants at different RWC values shows significant differences for only GGPPS and HPT1, with higher expression in the tolerant S. chilense. Chlorophyll, carotenoids, α‐tocopherol and ABA content was also determined in both species under different drought conditions. In agreement with HPT1 transcriptional activity, higher α‐tocopherol content was observed in S. chilense than in S. lycopersicum, which correlates with a lower degree of lipoperoxidation in the former species. These results suggest that, in addition to lower stomatal conductance, α‐tocopherol biosynthesis is part of the adaptation mechanisms of S. chilense to adverse environmental conditions.
Sulfur dioxide derivatives depress L‐type calcium channel in rat cardiomyocytes
Authors: Zhang Rong‐Yuan , Du Jun‐Bao , Sun Yan , Chen Stella , Tsai Hao‐Jan , Yuan Lan , Li Lin , Tang Chao‐Shu , Jin Hong‐Fang
Published: April 2011

1. Sulfur dioxide (SO2) has recently been found to have various biological effects on the cardiovascular system. The present study was designed to explore the effects of SO2 derivatives on the L‐type calcium current (I Ca, L) in isolated rat ventricular cardiomyocytes.

2. A Langendorf system was used to dissociate single ventricular cells. SO2 derivatives from 5 to 1000 μmol/L were incubated with cardiomyocytes. The whole‐cell patch‐clamp technique was used to record I Ca, L. The effect of SO2 derivatives on intracellular calcium concentration ([Ca2+]i) was detected by confocal microscopy.

3. Concentrations of 5 or 10 μmol/L SO2 derivatives could not change I Ca, L evoked by a single pulse from −40 to 0 mV for 200 ms in rat ventricular cardiomyocytes; however, 50, 100, 500 or 1000 μmol/L SO2 derivatives could depress the peak amplitudes of calcium currents in 6 min, and the I Ca, L was attenuated by 13.19%, 16.59%, 21.23% and 24.72%, respectively, as compared with corresponding controls (P < 0.05). The 50, 100, 500 or 1000 μmol/L SO2 derivatives also depressed the peak I‐V curves, without altering the reversal potential and the voltage dependence of the peak I Ca, L. Therefore, 1000 μmol/L SO2 derivatives could reduce [Ca2+]i in cardiomyocytes.

4. The results of the present study suggest that SO2 derivatives can depress I Ca, L in cardiomyocytes, which might have a protective effect in cardiovascular diseases.
Co‐administration of meso 2,3‐dimercaptosuccinic acid monoesters reduces arsenic concentration and oxidative stress in gallium arsenide exposed rats
Authors: Flora Swaran JS , Bhatt Kapil , Dwivedi Nidhi , Pachauri Vidhu , Kushwah Pramod K
Published: April 2011

1. Gallium arsenide (GaAs), a semiconductor, exerts toxicity as a result of its constitutive moieties; that is, gallium and arsenic that becomes dissociated after exposure. The present study focuses on reducing arsenic concentration from the target organs using monoesters of meso 2,3‐dimercaptosuccinic acid (DMSA) either individually or in combination.

2. Animals were exposed to GaAs (0.0014 mol/kg, orally for 8 weeks) and then treated with monoisoamyl DMSA (MiADMSA), monocyclohexyl DMSA (MchDMSA) or monomethyl DMSA (MmDMSA) either individually (0.3 mmol/kg, orally) or in combination (0.15 mmol/kg each, orally) for five consecutive days.

3. GaAs exposure significantly inhibited blood δ‐aminolevulinic acid dehydrogenase (ALAD), suggesting alterations in the heme synthesis pathway. Whereas a significant increase in blood, liver and kidney reactive oxygen species accompanied by an increase in lipid peroxidation points to the involvement of oxidative stress in GaAs toxicity.

4. GaAs also significantly disturbed glutathione metabolism. Hepatic and renal catalase activity decreased significantly, whereas hepatic and renal superoxide dismutase activity, as well as serum transaminases activity, showed marginal increase. Treatment with MiADMSA in combination with MchDMSA showed better therapeutic efficacy compared with other treatments in the aforementioned variables.

5. Co‐administration of MiADMSA with MchDMSA provided better therapeutic effects, including reduction of arsenic burden, compared with all other treatments.
Ferritin/alanine aminotransferase ratio as a possible marker for predicting the prognosis of acute liver injury
Authors: Ozawa Eisuke , Abiru Seigo , Nagaoka Shinya , Yano Koji , Komori Atsumasa , Migita Kiyoshi , Yatsuhashi Hiroshi , Taura Naota , Ichikawa Tatsuki , Ishibashi Hiromi , Nakao Kazuhiko
Published: April 2011

Background and Aims:  Serum levels of ferritin and heme oxygenase (HO)‐1 are both markers of macrophage activation. We evaluated simple markers for predicting the prognosis of severe acute liver injury in which macrophage activation plays an important role.

Methods:  Subjects comprised 114 patients with acute liver injury, admitted to the liver unit of Nagasaki Medical Center between January 2001 and September 2010. Subjects included 11 patients with fulminant hepatic failure (FHF), 82 patients with ordinary acute hepatitis (AH), and 21 patients with severe‐form AH (AHS). We determined serum levels of ferritin, HO‐1 and other biochemical makers, and analyzed relationships between clinical outcomes of patients and each of these parameters alone and in combination.

Results:  Median serum ferritin levels were significantly higher in FHF (25 900 ng/mL) and AHS (3060 ng/mL) than in AH (700 ng/mL; P < 0.01 each). Median HO‐1 levels were also significantly higher in FHF (123 ng/mL) and AHS (51 ng/mL) than in AH (19 ng/mL; P < 0.01 each). Similarly, median ferritin/alanine aminotransferase (F/A) ratio was significantly higher in FHF (6.7) than in AHS (1.6, P < 0.05) or AH (0.5, P < 0.01). Among the 11 FHF patients, three recovered, seven died and one underwent liver transplantation. The ability of F/A ratio to distinguish non‐survivors from survivors was analyzed using receiver operating characteristics curves. A cut‐off level of 3.12 provided high sensitivity (87.5%) and specificity (81.2%).

Conclusion:  These results suggest that F/A ratio offer a quick and simple marker for predicting the prognosis of acute liver injury.
Association of a single nucleotide polymorphism near the interleukin‐28B gene with response to hepatitis C therapy in Asian patients
Authors: Sinn Dong H , Kim Yu J , Lee Seung‐Tae , Gwak Geum‐Youn , Choi Moon S , Lee Joon H , Koh Kwang C , Yoo Byung C , Paik Seung W
Published: April 2011

Background and Aims:  A single nucleotide polymorphism near the interleukin‐28B (IL28B) gene has been shown to predict hepatitis C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients.

Methods:  A total of 118 patients (all Korean, 55 patients with genotype 1 infection and 63 patients with genotype 2 infection) were consecutively enrolled and analyzed.

Results:  The sustained virological response (SVR) rate was 74% (87/118), while 26 patients (22%) relapsed and five patients were non‐responders (4%). For rs8099917, the frequencies of major homozygotes (TT), heterozygotes (GT), and minor homozygotes (GG) were 0.85, 0.14 and 0.01, respectively. Of the 55 patients with HCV genotype 1 infection, the SVR rate was 67% and 44% (P = 0.19) and the non‐response rate was 2% and 22% (P = 0.015) for the major allele and minor or hetero allele, respectively. Of the 63 patients with HCV genotype 2 infection, the SVR rate was 80% and 100% (P = 0.13) and the non‐response rate was 4% and 0% (P = 0.55) for major allele and hetero allele, respectively.

Conclusions:  The IL28B genotype may help identify non‐responding patients in HCV genotype 1, but not in HCV genotype 2. Because of the high frequency of favorable alleles and the low frequency of non‐response, the IL28B polymorphism may play a smaller role in Asian patients.
Efficacy of therapy for advanced hepatocellular carcinoma: Intra‐arterial 5‐fluorouracil and subcutaneous interferon with image‐guided radiation
Authors: Chuma Makoto , Taguchi Hiroshi , Yamamoto Yoshiya , Shimizu Shinichi , Nakanishi Mitsuru , Ogawa Koji , Sho Takuya , Horimoto Hiromasa , Kobayashi Tomoe , Nakai Masato , Terashita Katsumi , Sakuhara Yusuke , Abo Daisuke , Tsukuda Yoko , Tsunematsu Seiji , Hige Shuhei , Kato Mototsugu , Shirato Hiroki , Asaka Masahiro
Published: April 2011

Background and Aim:  To evaluate the efficacy of intra‐arterial 5‐fluorouracil (5‐FU) and subcutaneous interferon (IFN) combined with image‐guided radiation therapy (IGRT) in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).

Methods:  Twenty HCC patients with PVTT were treated with 5‐FU and IFN combined with image‐guided radiation therapy (IGRT) (IGRT group), and as controls, 20 patients with PVTT were treated with 5‐FU and IFN alone (non‐IGRT group). Overall survival (OS) time, response rates, time to progression (TTP) and safety were compared across groups.

Results:  Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) of PVTT were 5%, 55%, 40% and 0% in the IGRT group and 0%, 30%, 35% and 35%, in the non‐IGRT group, respectively. CR, PR, SD, and PD of the whole tumor were 0%, 35%, 45% and 20% in the IGRT group and 0%, 30%, 35% and 35%, in the non‐IGRT group, respectively. Overall median survival was significantly longer in the IGRT group (12.0 months 95% confidence interval [CI], 9.3–17.6 months) than in the non‐IGRT group (9.1 months [95% CI, 5.5–11.1 months]) (P = 0.041). TTP was significantly longer in the IGRT group (6.9 months [95% CI, 5.6–10.2 months]) than in the non‐IGRT group (4.0 months [95% CI, 3.3–6.4 months]) (P = 0.034).

Conclusions:  The response rates, median OS time and TTP in patients with advanced HCC with PVTT who received this novel combination therapy of intra‐arterial 5‐FU and subcutaneous IFN with IGRT are encouraging, and this combination therapy warrants further investigation.
Pravastatin modulates liver bile acid and cholesterol homeostasis in rats with chronic cholestasis
Authors: Kolouchova Gabriela , Brcakova Eva , Hirsova Petra , Sispera Ludek , Tomsik Pavel , Cermanova Jolana , Hyspler Radek , Slanarova Martina , Fuksa Leos , Lotkova Halka , Micuda Stanislav
Published: April 2011

Background and Aim:  The administration of pravastatin to patients with cholestatic liver disease has suggested the potential of the drug with regard to reducing raised plasma cholesterol and bile acid levels. Information about the mechanisms associated with this effect is lacking. Thus, the aim of the present study is to evaluate pravastatin effects on the liver bile acid and cholesterol homeostasis in healthy and cholestatic rats.

Methods:  Control sham‐operated and reversibly bile duct‐obstructed (BDO) rats were treated with pravastatin (1 or 5 mg/kg) or the vehicle alone for 7 days after surgery.

Results:  Lower doses of pravastatin reduced bile acid plasma concentrations in cholestatic animals. The effect was associated with reduced liver mRNA expression of Cyp7a1, Cyp8b1, Mrp2, Ugt1a1 and the increased expression of Bsep. In addition, BDO‐induced increase in the liver content of cholesterol was normalized by pravastatin. The change was accompanied by the reduced liver expression of Hmg‐CoA reductase, LDL receptor, and Acat2, and induced the expression of Abca1 and Mdr2. These changes corresponded with the upregulation of nuclear receptors LXRα and PPARα, and the downregulation of FXR, CAR, SREBP‐2 and HNF1α. High doses of pravastatin lacked any positive effects on bile acids and cholesterol homeostasis, and blocked bile formation through the reduction of the biliary excretion of bile acids.

Conclusions:  Pravastatin rendered a positive reduction in BDO‐induced increases in plasma bile acid concentrations and cholesterol liver content, mainly through the transcriptionally‐mediated downregulation of genes involved in the synthesis of these compounds in the liver.
The economics of robotic cystectomy: cost comparison of open versus robotic cystectomy
Authors: Lee Richard , Ng Casey K. , Shariat Shahrokh F. , Borkina Anna , Guimento Robert , Brumit Kevin F. , Scherr Douglas S.
Published: April 2011

Study Type – Therapy (cost minimisation)

Level of Evidence 2b

OBJECTIVE

• To assess and compare the economic burden of open radical cystectomy (OC) vs robotic‐assisted laparoscopic radical cystectomy (RC) with pelvic lymph node dissection and urinary diversion.

PATIENTS AND METHODS

• A series of 103 and 83 consecutive patients undergoing OC and RC, respectively, were prospectively studied at a tertiary care institution from April 2002 to February 2009.

• Data were collected on patient demographics, perioperative parameters and length of stay (LOS) in hospital. Cohorts were subdivided into ileal conduit (IC), continent cutaneous diversion (CCD) and orthotopic neobladder (ON) subgroups.

• A linear cost model was created to simulate treatment with OC vs RC. Procedural costs were derived from the Medicare Resource Based Relative Value Scale. Materials costs were obtained from the respective suppliers. The indirect costs of complications were considered.

• Sensitivity analyses were performed.

RESULTS

• Despite a higher cost of materials, RC was less expensive than OC for IC and CCD, although the cost advantage deteriorated for ON.

• The per‐case costs of RC with IC, CCD and ON were $20 659, $22 102 and $22 685, respectively, compared to $25 505, $22 697 and $20 719 for their OC counterparts.

• The largest cost driver in the study was LOS in hospital.

• RC showed a shorter LOS compared to OC, although this effect was insufficient to offset the higher cost of robotic surgery.

• Complications materially affected cost performance.

CONCLUSIONS

• Despite a higher cost of materials, RC can be more cost efficient than OC as a treatment for bladder cancer at a high‐volume, tertiary care referral centre, particularly with IC.

• Complications significantly impact cost performance.
Can stochastic geographical evolution re‐create macroecological richness–environment correlations?
Authors: Tello J. Sebastián , Stevens Richard D.
Published: April 2011

Aim Richness gradients are frequently correlated with environmental characteristics at broad geographic scales. In particular, richness is often associated with energy and climate, while environmental heterogeneity is rarely its best correlate. These correlations have been interpreted as evidence in favour of environmental determinants of diversity gradients, particularly energy and climate. This interpretation assumes that the expected‐by‐random correlation between richness and environment is zero, and that this is equally true for all environmental characteristics. However, these expectations might be unrealistic. We investigated to what degree basic evolutionary/biogeographical processes occurring independently of environment could lead to richness gradients that correlate with environmental characteristics by chance alone.

Location Africa, Australia, Eurasia and the New World.

Methods We produced artificial richness gradients based on a stochastic simulation model of geographic diversification of clades. In these simulations, species speciate, go extinct and expand or shift their distributions independently of any environmental characteristic. One thousand two hundred repetitions of this model were run, and the resulting stochastic richness gradients were regressed against real‐world environmental variables. Stochastic species–environment relationships were then compared among continents and among three environmental characteristics: energy, environmental heterogeneity and climate seasonality.

Results Simulations suggested that a significant degree of correlation between richness gradients and environment is expected even when clades diversify and species distribute stochastically. These correlations vary considerably in strength; but in the best cases, environment can spuriously account for almost 80% of variation in stochastic richness. Additionally, expected‐by‐chance relationships were different among continents and environmental characteristics, producing stronger spurious relationships with energy and climate than with heterogeneity.

Main conclusions We conclude that some features of empirical species–environment relationships can be reproduced just by chance when taking into account evolutionary/biogeographical processes underlying the construction of species richness gradients. Future tests of environmental effects on richness should consider structure in richness–environment correlations that can be produced by simple evolutionary null models. Research should move away from the naive non‐biological null hypotheses that are implicit in traditional statistical tests.
Processes at multiple scales affect richness and similarity of non‐native plant species in mountains around the world
Authors: Seipel Tim , Kueffer Christoph , Rew Lisa J. , Daehler Curtis C. , Pauchard Aníbal , Naylor Bridgett J. , Alexander Jake M. , Edwards Peter J. , Parks Catherine G. , Arevalo José Ramon , Cavieres Lohengrin A. , Dietz Hansjörg , Jakobs Gabi , McDougall Keith , Otto Rüdiger , Walsh Neville
Published: April 2011

Aim To investigate how species richness and similarity of non‐native plants varies along gradients of elevation and human disturbance.

Location Eight mountain regions on four continents and two oceanic islands.

Methods We compared the distribution of non‐native plant species along roads in eight mountainous regions. Within each region, abundance of plant species was recorded at 41–84 sites along elevational gradients using 100‐m2plots located 0, 25 and 75 m from roadsides. We used mixed‐effects models to examine how local variation in species richness and similarity were affected by processes at three scales: among regions (global), along elevational gradients (regional) and with distance from the road (local). We used model selection and information criteria to choose best‐fit models of species richness along elevational gradients. We performed a hierarchical clustering of similarity to investigate human‐related factors and environmental filtering as potential drivers at the global scale.

Results Species richness and similarity of non‐native plant species along elevational gradients were strongly influenced by factors operating at scales ranging from 100 m to 1000s of km. Non‐native species richness was highest in the New World regions, reflecting the effects of colonization from Europe. Similarity among regions was low and due mainly to certain Eurasian species, mostly native to temperate Europe, occurring in all New World regions. Elevation and distance from the road explained little of the variation in similarity. The elevational distribution of non‐native species richness varied, but was always greatest in the lower third of the range. In all regions, non‐native species richness declined away from roadsides. In three regions, this decline was steeper at higher elevations, and there was an interaction between distance and elevation.

Main conclusions Because non‐native plant species are affected by processes operating at global, regional and local scales, a multi‐scale perspective is needed to understand their patterns of distribution. The processes involved include global dispersal, filtering along elevational gradients and differential establishment with distance from roadsides.
Agonism and the Reconception of European Citizenship
Authors: Tambakaki Paulina
Published: April 2011

Viewed either as a limited undertaking or a process in the making, European citizenship appears to be caught at an impasse. While the dominant approaches fail to break from the confines of the demos/no demos thesis, the challenges confronting Union citizenship ironically converge with those posed to citizenship discourse. Can European citizenship escape from this impasse? To address this question the article shows how the agonistic emphasis on contestation opens the way for a different reading of European citizenship. On this reading, Union citizenship is not simply taken as a means to participation, but as a channel for political mobilisation. Constructed out of an affective identification with the negative, with that we oppose rather than endorse, the agonistic conception, argues the article, insightfully shifts the terms of debating Union citizenship.
Netwar Geopolitics: Security, Failed States and Illicit Flows
Authors: Bourne Mike
Published: April 2011

Recent and emerging security policies and practices claim a mutual vulnerability that closely links human insecurity in failed states with the threat to powerful states from illicit flows. This article first examines this ‘emerging orthodoxy’ of transnational security issues that reinforces the securitisation of poverty and the poor. It then subjects this orthodoxy to theoretical and empirical critique. Theoretically it shows that this orthodoxy is formed as a ‘geopolitical imagination’ that associates and stabilises particular views of weak states and illicit flows in a ‘netwar imagination’ by reasserting and reconfiguring traditional assumptions of the spatiality and nature of threats. A final empirical section, focusing on drug production and nuclear smuggling, argues that those assumptions and their assemblage are a partial, incomplete and often self-referential reading of illicit flows.
The effects of humor and depression labels on reactions to social comments
Authors: IBARRA‐ROVILLARD M. SOL , KUIPER NICHOLAS A.
Published: April 2011

Ibarra‐Rovillard, M. S. & Kuiper, N. A. (2011). The effects of humor and depression labels on reactions to social comments. Scandinavian Journal of Psychology 52, 448–456.

Humor is generally considered to facilitate social relationships, whereas depression has been related to difficulties in relationships. This study investigated the effects of labeling social comments as humorous, as well as labeling the presenter of the comments as feeling depressed, on recipients’ reactions to these comments. To this end, 350 university students were presented with vignettes describing four styles of comments (i.e., affiliative, self‐enhancing, self‐defeating, and aggressive) made by a casual acquaintance. Participants were randomly assigned to one of four conditions. These conditions varied in terms of whether the four styles of comments were described as humorous or not, and whether the acquaintance making the comments was described as feeling depressed or not. Findings indicated that humor led to more positive reactions. Labeling the acquaintance as depressed led to more negative reactions than when the acquaintance was labeled non‐depressed, particularly when the comments were self‐defeating. Interestingly, when the acquaintance was described as feeling depressed, affiliative comments made in a humorous fashion led to more positive reactions than did non‐humorous affiliative comments. These findings are discussed in terms of the effects of humor and depression on interpersonal interactions.
Oxidative stress: a bridge between migraine and cardiovascular disease?
Authors: Sacco S. , Carolei A.
Published: April 2011

Click here to view the accompanying paper in this issue.
Participatory Budgeting in Italy: An Analysis of (Almost Democratic) Participatory Governance Arrangements
Authors: BASSOLI MATTEO
Published: April 2011

This article addresses definitory problems concerning participatory budgeting (PB), the purpose being to underline the governance nature of this instrument. More specifically, considering PB as a particular type of participatory governance arrangement, it focuses on the democratic outcomes of concrete experiences. Adopting the Dahlian process‐oriented concept of democracy, three Italian cases are depicted and analysed, according to four critical variables: inclusion, participation, the role of the opposition, and transparency. This enables full description of how PB affects local democracy, both positively and negatively. The article concludes by highlighting two variables that give account of the democratic implications of these practices: the role of the political leadership, and the inclusive strategy adopted. Further, it underlines three additional factors that embody what is commonly referred to as political investment in public–private partnerships: an active role for the opposition, outward communication, and effective participation. While assessing the democratic outcomes, the study highlights how the presence and maintenance of these practices are linked to the role played by civil society and the presence of administrative ties.

Cet article porte sur des problèmes de définition liés au ‘budget participatif’, l'objectif étant de souligner que cet instrument relève de la gouvernance. Plus précisément, en le présentant comme un type particulier de dispositif de gouvernance participative, l'étude s'intéresse aux résultats démocratiques d'expériences concrètes. Reprenant le processus défini par le concept de démocratie de Dahl, trois cas italiens sont présentés et analysés en fonction de quatre variables critiques: inclusion, participation, rôle de l'opposition, transparence. Il est ainsi possible de décrire précisément l'impact, tant positif que négatif, du budget participatif sur la démocratie locale. La conclusion met en avant deux variables qui rendent compte des implications démocratiques de ces pratiques: le rôle des autorités politiques et la stratégie d'inclusion adoptée. En outre, elle souligne trois autres facteurs qui traduisent ce qu'on appelle couramment l'investissement politique dans les partenariats public‐privé: le rôle actif de l'opposition, une communication extérieure et une participation efficace. Tout en évaluant les résultats démocratiques, l'étude montre comment la présence et la continuité de ces pratiques sont liées au rôle de la société civile et à l'existence de connexions administratives.
Small molecule analysis and imaging of fatty acids in the zebra finch song system using time‐of‐flight‐secondary ion mass spectrometry
Authors: Amaya Kensey R. , Sweedler Jonathan V. , Clayton David F.
Published: April 2011

J. Neurochem. (2011) 118, 499–511.

Fatty acids are central to brain metabolism and signaling, but their distributions within complex brain circuits have been difficult to study. Here we applied an emerging technique, time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS), to image specific fatty acids in a favorable model system for chemical analyses of brain circuits, the zebra finch (Taeniopygia guttata). The zebra finch, a songbird, produces complex learned vocalizations under the control of an interconnected set of discrete, dedicated brain nuclei ‘song nuclei’. Using ToF‐SIMS, the major song nuclei were visualized by virtue of differences in their content of essential and non‐essential fatty acids. Essential fatty acids (arachidonic acid and docosahexaenoic acid) showed distinctive distributions across the song nuclei, and the 18‐carbon fatty acids stearate and oleate discriminated the different core and shell subregions of the lateral magnocellular nucleus of the anterior nidopallium. Principal component analysis of the spectral data set provided further evidence of chemical distinctions between the song nuclei. By analyzing the robust nucleus of the arcopallium at three different ages during juvenile song learning, we obtain the first direct evidence of changes in lipid content that correlate with progression of song learning. The results demonstrate the value of ToF‐SIMS to study lipids in a favorable model system for probing the function of lipids in brain organization, development and function.
Loss of intestinal nuclei and intestinal integrity in aging C. elegans
Authors: McGee Matthew D. , Weber Darren , Day Nicholas , Vitelli Cathy , Crippen Danielle , Herndon Laura A. , Hall David H. , Melov Simon
Published: April 2011

The roundworm C. elegans is widely used as an aging model, with hundreds of genes identified that modulate aging (Kaeberlein et al., 2002. Mech. Ageing Dev.123, 1115–1119). The development and bodyplan of the 959 cells comprising the adult have been well described and established for more than 25 years (Sulston & Horvitz, 1977. Dev. Biol.56, 110–156; Sulston et al., 1983. Dev. Biol.100, 64–119.). However, morphological changes with age in this optically transparent animal are less well understood, with only a handful of studies investigating the pathobiology of aging. Age‐related changes in muscle (Herndon et al., 2002. Nature419, 808–814), neurons (Herndon et al., 2002), intestine and yolk granules (Garigan et al., 2002. Genetics161, 1101–1112; Herndon et al., 2002), nuclear architecture (Haithcock et al., 2005. Proc. Natl Acad. Sci. USA102, 16690–16695), tail nuclei (Golden et al., 2007. Aging Cell6, 179–188), and the germline (Golden et al., 2007) have been observed via a variety of traditional relatively low‐throughput methods. We report here a number of novel approaches to study the pathobiology of aging C. elegans. We combined histological staining of serial‐sectioned tissues, transmission electron microscopy, and confocal microscopy with 3D volumetric reconstructions and characterized age‐related morphological changes in multiple wild‐type individuals at different ages. This enabled us to identify several novel pathologies with age in the C. elegans intestine, including the loss of critical nuclei, the degradation of intestinal microvilli, changes in the size, shape, and cytoplasmic contents of the intestine, and altered morphologies caused by ingested bacteria. The three‐dimensional models we have created of tissues and cellular components from multiple individuals of different ages represent a unique resource to demonstrate global heterogeneity of a multicellular organism.
MicroRNA‐18 and microRNA‐19 regulate CTGF and TSP‐1 expression in age‐related heart failure
Authors: van Almen Geert C. , Verhesen Wouter , van Leeuwen Rick E. W. , van de Vrie Mathijs , Eurlings Casper , Schellings Mark W. M. , Swinnen Melissa , Cleutjens Jack P. M. , van Zandvoort Marc A. M. J. , Heymans Stephane , Schroen Blanche
Published: April 2011

To understand the process of cardiac aging, it is of crucial importance to gain insight into the age‐related changes in gene expression in the senescent failing heart. Age‐related cardiac remodeling is known to be accompanied by changes in extracellular matrix (ECM) gene and protein levels. Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of ECM proteins. However, their role in age‐related cardiac remodeling and heart failure is unknown. In this study, we investigated the aging‐associated microRNA cluster 17–92, which targets the ECM proteins connective tissue growth factor (CTGF) and thrombospondin‐1 (TSP‐1). We employed aged mice with a failure‐resistant (C57Bl6) and failure‐prone (C57Bl6 × 129Sv) genetic background and extrapolated our findings to human age‐associated heart failure. In aging‐associated heart failure, we linked an aging‐induced increase in the ECM proteins CTGF and TSP‐1 to a decreased expression of their targeting microRNAs 18a, 19a, and 19b, all members of the miR‐17–92 cluster. Failure‐resistant mice showed an opposite expression pattern for both the ECM proteins and the microRNAs. We showed that these expression changes are specific for cardiomyocytes and are absent in cardiac fibroblasts. In cardiomyocytes, modulation of miR‐18/19 changes the levels of ECM proteins CTGF and TSP‐1 and collagens type 1 and 3. Together, our data support a role for cardiomyocyte‐derived miR‐18/19 during cardiac aging, in the fine‐tuning of cardiac ECM protein levels. During aging, decreased miR‐18/19 and increased CTGF and TSP‐1 levels identify the failure‐prone heart.
Conventional versus acupuncture‐like transcutaneous electrical nerve stimulation on cold‐induced pain in healthy human participants: effects during stimulation
Authors: Francis Richard P. , Marchant Paul , Johnson Mark I.
Published: April 2011

Objectives:  To compare the hypoalgesic effects of conventional transcutaneous electrical nerve stimulation (TENS) (high frequency, low intensity) and acupuncture‐like TENS (AL‐TENS, low frequency, high intensity) on cold‐induced pain.

Design:  Randomized controlled parallel group study comparing the effects of strong non‐painful AL‐TENS, conventional TENS and placebo (no current) TENS on cold‐pressor pain threshold (CPT) and pain intensity. Two baseline (pre‐intervention) measures and three during intervention measures of CPT and cold pain intensity (four point category scale) were recorded.

Setting:  Physiology laboratory in Leeds Metropolitan University.

Participants:  One hundred and twenty‐one healthy participants.

Interventions:  Each participant received one of three TENS interventions over their flexor digitorum profundus: (i) high pulse rate TENS with a strong non‐painful paraesthesia (conventional), (ii) low‐rate burst mode TENS that caused strong non‐painful phasic muscle twitching (acupuncture like) or (iii) no current (placebo) TENS.

Main outcome measure:  Difference between conventional TENS and AL‐TENS in cold pain threshold relative to pre‐TENS baseline after 25 min of stimulation.

Results:  No differences were detected for CPT or cold pain intensity during conventional TENS compared with AL‐TENS. When compared with placebo TENS, the confidence intervals for the ratio of intervention CPT to baseline CPT, for both AL‐TENS (0·966, 1·424) and conventional TENS (0·948, 1·401), were close to the positive side of one, although neither reached statistical significance.

Conclusions:  Unlike some previous studies, the present study detected no differences in hypoalgesia between AL‐TENS, conventional TENS and placebo (no current) TENS during stimulation.
The selective anandamide transport inhibitor VDM11 attenuates reinstatement of nicotine seeking behaviour, but does not affect nicotine intake
Authors: Gamaleddin Islam , Guranda Mihail , Goldberg Steven R , Le Foll Bernard
Published: April 2011

BACKGROUND AND PURPOSE The endocannabinoid system appears to play a pivotal role in mediating the rewarding and reinforcing effects of nicotine. Recent studies have shown that the inhibition of fatty acid amide hydrolase (FAAH) attenuates reinstatement of nicotine‐seeking induced by nicotine priming and nicotine‐associated cues. FAAH hydrolyses the endogenous endocannabinoid anandamide, as well as other non‐cannabinoid ligands such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). As OEA and PEA can attenuate both nicotine‐taking and nicotine‐seeking behaviour, the specific role of anandamide remains unclear. In this study, we have tested the selective anadamide uptake inhibitor, VDM11, which elevates anandamide levels without affecting levels of OEA/PEA, on nicotine‐taking and nicotine‐seeking behaviour.

EXPERIMENTAL APPROACH We used a nicotine intravenous self‐administration model in rats to assess the effect of VDM11, given i.p., on nicotine taking using fixed and progressive ratio schedules of reinforcement as well as on reinstatement of nicotine‐seeking induced by nicotine priming and nicotine‐associated cues.

KEY RESULTS VDM11 did not affect levels of responding for nicotine under fixed‐ratio and progressive‐ratio schedules of reinforcement. In contrast, VDM11 dose‐dependently attenuated reinstatement of nicotine‐seeking behaviour induced by nicotine‐associated cues and nicotine priming.

CONCLUSIONS AND IMPLICATIONS These results indicate that ligands elevating anandamide levels could have therapeutic value for preventing relapse into nicotine‐seeking behaviour and should be tested in humans trying to quit smoking.