bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis of users' behaviour patterns in the organisation of information
Authors: Chen Ya‐Ning , Ke Hao‐Ren
Published: August 2013

Purpose

The purpose of this paper is to investigate the behaviour preferences and patterns of the organisation of information by taggers, including usage of tags, tag categories and implicit patterns embedded in social tags.

Design/methodology/approach

The sample was 4,390 social tags (1,777 unique) from 1,661 articles published in 16 library and information science journals selected from CiteULike between February and March 2011. Using application profiles, a tag category model served as a framework to develop two sets of hybrid tag categories for analysing the distribution of tag categories and their implicit patterns.

Findings

The frequency of tag categories was consistent with that of individual tags and obeyed a power law distribution. In total, six implicit patterns embedded in tags – syntactical, semantic, mnemonic, genre, contextual hybrid relations and split term – were discovered.

Research limitations/implications

Although this study focused solely on investigating taggers' behaviour preferences and patterns, the results of this study may shed light on tagging practice, query formulation and construction of controlled vocabularies.

Originality/value

A set of hybrid tag categories consisting of title, function, content and topic‐related categories is proposed to delineate the distribution of social tags and taggers' behaviour preferences, and implicit patterns embedded in tags are generalised. These patterns may be useful for tagging practice, query formulation and construction of controlled vocabularies.
Corporate financial communication and the internet: manipulating investor audiences?
Authors: Guillamón‐Saorín Encarna , Martínez‐López Francisco J.
Published: August 2013

Purpose

The aim of this paper is to contribute to the understanding of how the internet interacts with businesses and markets. The authors aims to focus on the internet press releases of annual results to illustrate how corporate communication is used and managed strategically online.

Design/methodology/approach

The authors describe the increasing importance of the internet for communicating firms' performance to investors, financial media and the stock market, then identify and discuss a number of techniques that might be used to potentially manipulate the online presentation of financial results. Thus the authors conducted a content analysis of the internet press releases in two consecutive years (2008 and 2009) by a wide range of companies listed in the IBEX 35 share index.

Findings

This paper provides in‐depth insights into content analysis techniques by providing examples of how potentially misleading disclosure practices are included in press releases. Moreover the paper investigates the use of seven potentially misleading disclosure practices appearing in press releases that optimise the way in which company results are presented.

Practical implications

Regulators may consider the normalisation of the content of internet press releases to avoid or reduce opportunistic disclosure practices. Moreover, investors should be aware of the use of these practices to reduce the misleading effect when processing corporate information.

Originality/value

This pioneering study analyses and provides evidence of potentially misleading internet‐based disclosure strategies. Furthermore the paper proposes a set of measures for corporate information presentation.
Effect of maxillary osteotomy on speech in cleft lip and palate: perceptual outcomes of velopharyngeal function
Authors: Pereira Valerie J. , Sell Debbie , Tuomainen Jyrki
Published: August 2013

Background

Abnormal facial growth is a well‐known sequelae of cleft lip and palate (CLP) resulting in maxillary retrusion and a class III malocclusion. In 10–50% of cases, surgical correction involving advancement of the maxilla typically by osteotomy methods is required and normally undertaken in adolescence when facial growth is complete. Current evidence for the impact of the surgery on velopharyngeal function is weak and mixed.

Aims

The first objective of the study was to investigate the nature of the effect of maxillary osteotomy on the perceptual outcomes of velopharyngeal function in CLP. The second objective was to establish if speech changes seen early at 3 months post‐operation persisted for a year after/following surgery’, when it is considered that the maxilla is relatively stable.

Methods & Procedures

Twenty consecutive patients with CLP undergoing maxillary osteotomy by a single surgeon were seen pre‐operatively (T1), 3 months (T2) and 12 months (T3) post‐operation. A non‐cleft control group (NonCLP) undergoing surgery was also recruited. Speech data were collected using the Cleft Audit Protocol for Speech—Augmented (CAPS‐A). A velopharyngeal composite score‐summary (VPC‐SUM) was derived from specific CAPS‐A‐rated parameters. An external CAPS‐A‐trained therapist, blinded to the study, rated the randomized samples and inter‐rater reliability was established.

Outcomes & Results

For the CLP group, hypernasality and nasal turbulence increased significantly post‐operation. Planned comparisons were significant for T1–T2 only with a medium effect size. For hypernasality, the CLP group differed statistically from the NonCLP group at T2 and T3. For nasal turbulence, the CLP group differed statistically from the NonCLP group at T2. For VPC‐SUM, there were statistically significant changes post‐operatively between T1–T2 and T1–T3 only with medium effect sizes for the CLP group only.

Conclusions & Implications

This study provides evidence that maxillary osteotomy affects patients with and without CLP differently. In patients with CLP, surgery may impact negatively on velopharyngeal function for speech and changes seen early on at 3 months post‐operatively appear to persist at 12 months postoperatively. The findings in this study have implications for the speech care pathway of patients with CLP undergoing maxillary osteotomy in terms of assessment, review and management.
SITUATIONAL CAUSES OF OFFENDING: A FIXED‐EFFECTS ANALYSIS OF SPACE–TIME BUDGET DATA
Authors: BERNASCO WIM , RUITER STIJN , BRUINSMA GERBEN J.N. , PAUWELS LIEVEN J.R. , WEERMAN FRANK M.
Published: August 2013

Situational theories of crime assert that the situations that people participate in contain the proximal causes of crime. Prior research has not tested situational hypotheses rigorously, either for lack of detailed situational data or for lack of analytical rigor. The present research combines detailed situational data with analytical methods that eliminate all stable between‐individual factors as potential confounds. We test seven potential situational causes: 1) presence of peers, 2) absence of adult handlers, 3) public space, 4) unstructured activities, 5) use of alcohol, 6) use of cannabis, and 7) carrying weapons. In a two‐wave panel study, a general sample of adolescents completed a space–time budget interview that recorded, hour by hour over the course of 4 complete days, the activities and whereabouts of the subjects, including any self‐reported offenses. In total, 76 individuals reported having committed 104 offenses during the 4 days covered in the space–time budget interview. Using data on the 4,949 hours that these 76 offenders spent awake during these 4 days, within‐individual, fixed‐effects multivariate logit analyses were used to establish situational causes of offending. The findings demonstrate that offending is strongly and positively related to all hypothesized situational causes except using cannabis and carrying weapons.
BRAF V600EMutation Is Associated withmTORSignaling Activation in Glioneuronal Tumors
Authors: Prabowo Avanita S. , Iyer Anand M. , Veersema Tim J. , Anink Jasper J. , Schouten‐van Meeteren Antoinette Y. N. , Spliet Wim G. M. , van Rijen Pieter C. , Ferrier Cyrille H. , Capper David , Thom Maria , Aronica Eleonora
Published: August 2013

BRAF V600Emutations have been recently reported in glioneuronal tumors (GNTs). To evaluate the expression of theBRAF V600Emutated protein and its association with activation of the mammalian target of rapamycin (mTOR) pathway, immunophenotype and clinical characteristics inGNTs, we investigated a cohort of 174GNTs. The presence ofBRAF V600Emutations was detected by directDNAsequencing andBRAF V600Eimmunohistochemical detection. Expression ofBRAF‐mutated protein was detected in 38/93 (40.8%) gangliogliomas (GGs), 2/4 (50%) desmoplastic infantile gangliogliomas (DIGs) and 23/77 (29.8%) dysembryoplastic neuroepithelial tumors (DNTs) by immunohistochemistry. In bothGGsandDNTs, the presence ofBRAF V600Emutation was significantly associated with the expression ofCD34, phosphorylated ribosomalS6protein (pS6; marker ofmTORpathway activation) in dysplastic neurons and synaptophysin (P < 0.05). InGGs, the presence of lymphocytic cuffs was more frequent inBRAF‐mutated cases (31 vs. 15.8%;P = 0.001). The expression of bothBRAF V600EandpS6was associated with a worse postoperative seizure outcome inGNT(P < 0.001). Immunohistochemical detection ofBRAF V600E‐mutated protein may be valuable in the diagnostic evaluation of these glioneuronal lesions and the observed association withmTORactivation may aid in the development of targeted treatment involving specific pathogenic pathways.
Indirect activation of the SV23 and SV24 splice variants of human constitutive androstane receptor: analysis with 3‐hydroxyflavone and its analogues
Authors: Lau Aik Jiang , Chang Thomas K H
Published: August 2013

Background and Purpose

Naturally occurring splice variants of human CAR (hCAR), including hCAR‐SV23 (insertion of amino acids SPTV) and hCAR‐SV24 (APYLT), have been shown to be expressed in liver. However, little is known regarding how hCAR‐SV23 and hCAR‐SV24 are activated. Therefore, we investigated the mode of activation of these hCAR splice variants.

Experimental Approach

Cell‐based reporter gene assays, including ligand‐binding domain transactivation assays and coactivator recruitment assays, were conducted on cultured HepG2 cells transfected with various constructs and treated with 3‐hydroxyflavone or a hydroxylated (galangin, datiscetin, kaempferol, morin, quercetin or myricetin) or methylated (isorhamnetin, tamarixetin, or syringetin) analogue.

Key Results

Among the flavonols investigated, only 3‐hydroxyflavone increased hCAR‐SV23 and hCAR‐SV24 activities. 3‐Hydroxyflavone did not transactivate the ligand‐binding domain of these isoforms or recruit steroid receptor coactivators (SRC‐1, SRC‐2, or SRC‐3). By comparison, 3‐hydroxyflavone, galangin, datiscetin, kaempferol, quercetin, isorhamnetin and tamarixetin activated hCAR‐WT, whereas none of the flavonols activated hCAR‐SV25 (both SPTV and APYLT insertions). The flavonols 3‐Hydroxyflavone, galangin, quercetin and tamarixetin transactivated the ligand‐binding domain of hCAR‐WT, but only 3‐hydroxyflavone recruited SRC‐1, SRC‐2 and SRC‐3 to the receptor.

Conclusion and Implications

hCAR‐SV23 and hCAR‐SV24 can be activated by a mechanism that does not involve the ligand‐binding domain of the receptor or recruitment of SRC‐1, SRC‐2, or SRC‐3. 3‐Hydroxyflavone and its structural analogues activated hCAR in an isoform‐selective and chemical‐specific manner. Overall, our study provides insight into a novel mode of ligand activation of hCAR‐SV23 and hCAR‐SV24.
Combined subthreshold dose inhibition of myosin light chain phosphorylation and MMP‐2 activity provides cardioprotection from ischaemic/reperfusion injury in isolated rat heart
Authors: Cadete Virgilio J J , Sawicka Jolanta , Bekar Lane K , Sawicki Grzegorz
Published: August 2013

Background and Purpose

Phosphorylation and degradation of myosin light chain 1 (MLC1) during myocardial ischaemia/reperfusion (I/R) injury is a well‐established phenomenon. It has been established that MMP‐2 is involved in MLC1 degradation and that this degradation is increased when MLC1 is phosphorylated. We hypothesized that simultaneous inhibition of MLC1 phosphorylation and MMP‐2 activity will protect hearts from I/R injury. As phosphorylation of MLC1 and MMP‐2 activity is important for normal heart function, we used a cocktail consisting combination of low (subthreshold for any protective effect alone) doses of MLC kinase, MMP‐2 inhibitors and subthreshold dose of an MLC phosphatase activator.

Experimental Approach

Isolated rat hearts were subjected to 20 min of global, no‐flow ischaemia and 30 min reperfusion in the absence and presence of inhibitors of MLC1 phosphorylation and degradation.

Key Results

The recovery of cardiac function was improved in a concentration‐dependent manner by the MLC kinase inhibitor, ML‐7 (1–5 μM), the MLC phosphatase activator, Y‐27632 (0.05–1 μM) or the MMP inhibitor, doxycycline (Doxy, 1–30 μM). Co‐administration of subthreshold doses of ML‐7 (1 μM) and Y‐27632 (0.05 μM) showed a potential synergistic effect in protecting cardiac contractility and MLC1 levels in I/R hearts. Further combination with a subthreshold concentration of Doxy (1 μM) showed additional protection that resulted in full recovery to control levels.

Conclusions and Implications

The results of this study exemplify a novel low‐dose multidrug approach to pharmacological prevention of reperfusion injury that will enable a reduction of unwanted side effects and/or cytotoxicity associated with currently available MMP‐2 and kinase inhibiting drugs.
Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis
Authors: González‐García C , Bravo B , Ballester A , Gómez‐Pérez R , Eguiluz C , Redondo M , Martínez A , Gil C , Ballester S
Published: August 2013

Background and Purpose

PDE4 inhibition suppresses experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, side effects hinder PDE4 inhibitors clinical use. PDE7 inhibition might constitute an alternative therapeutic strategy, but few data about the anti‐inflammatory potential of PDE7 inhibitors are currently available. We have used the EAE model to perform a comparative evaluation of PDE4 and PDE7 inhibition as strategies for MS treatment.

Experimental Approach

Two PDE7 inhibitors, the sulfonamide derivative BRL50481 and the recently described quinazoline compound TC3.6, were assayed to modulate EAE in SJL mice, in comparison with the well‐known PDE4 inhibitor Rolipram. We evaluated clinical signs, presence of inflammatory infiltrates in CNS and anti‐inflammatory markers. We also analysed the effect of these inhibitors on the inflammatory profile of spleen cells in vitro.

Key Results

TC3.6 prevented EAE with efficacy similar to Rolipram, while BRL50481 had no effect on the disease. Differences between both PDE7 inhibitors are discussed. Data from Rolipram and TC3.6 showed that PDE4 and PDE7 inhibition work through both common and distinct pathways. Rolipram administration caused an increase in IL‐10 and IL‐27 expression which was not found after TC3.6 treatment. On the other hand, both inhibitors reduced IL‐17 levels, prevented infiltration in CNS and increased the expression of the T regulator cell marker Foxp3.

Conclusions and Implications

These results provide new information about the effects of Rolipram on EAE, underline PDE7 inhibition as a new therapeutic target for inflammatory diseases and show the value of TC3.6 to prevent EAE, with possible consequences for new therapeutic tools in MS.
Epigenetic control of skin differentiation genes by phytocannabinoids
Authors: Pucci Mariangela , Rapino Cinzia , Di Francesco Andrea , Dainese Enrico , D'Addario Claudio , Maccarrone Mauro
Published: August 2013

Background and Purpose

Endocannabinoid signalling has been shown to have a role in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we investigated the possible epigenetic regulation of these genes by several phytocannabinoids, plant‐derived cannabinoids that have the potential to be novel therapeutics for various human diseases.

Experimental Approach

The effects of cannabidiol, cannabigerol and cannabidivarin on the expression of skin differentiation genes keratins 1 and 10, involucrin and transglutaminase 5, as well as on DNA methylation of keratin 10 gene, were investigated in human keratinocytes (HaCaT cells). The effects of these phytocannabinoids on global DNA methylation and the activity and expression of four major DNA methyltransferases (DNMT1, 3a, 3b and 3L) were also examined.

Key Results

Cannabidiol and cannabigerol significantly reduced the expression of all the genes tested in differentiated HaCaT cells, by increasing DNA methylation of keratin 10 gene, but cannabidivarin was ineffective. Remarkably, cannabidiol reduced keratin 10 mRNA through a type‐1 cannabinoid (CB1) receptor‐dependent mechanism, whereas cannabigerol did not affect either CB1 or CB2 receptors of HaCaT cells. In addition, cannabidiol, but not cannabigerol, increased global DNA methylation levels by selectively enhancing DNMT1 expression, without affecting DNMT 3a, 3b or 3L.

Conclusions and Implications

These findings show that the phytocannabinoids cannabidiol and cannabigerol are transcriptional repressors that can control cell proliferation and differentiation. This indicates that they (especially cannabidiol) have the potential to be lead compounds for the development of novel therapeutics for skin diseases.
Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives
Authors: Herradón G , Pérez‐García C
Published: August 2013

Midkine (MK) and pleiotrophin (PTN) are two neurotrophic factors that are highly up‐regulated in different brain regions after the administration of various drugs of abuse and in degenerative areas of the brain. A deficiency in both MK and PTN has been suggested to be an important genetic factor, which confers vulnerability to the development of the neurodegenerative disorders associated with drugs of abuse in humans. In this review, evidence demonstrating that MK and PTN limit the rewarding effects of drugs of abuse and, potentially, prevent drug relapse is compiled. There is also convincing evidence that MK and PTN have neuroprotective effects against the neurotoxicity and development of neurodegenerative disorders induced by drugs of abuse. Exogenous administration of MK and/or PTN into the CNS by means of non‐invasive methods is proposed as a novel therapeutic strategy for addictive and neurodegenerative diseases. Identification of new molecular targets downstream of the MK and PTN signalling pathways or pharmacological modulation of those already known may also provide a more traditional, but probably effective, therapeutic strategy for treating addictive and neurodegenerative disorders.

Linked Articles

This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐4
Molecular mechanisms underlying physiological and receptor pleiotropic effects mediated by GLP‐1R activation
Authors: Pabreja K , Mohd M A , Koole C , Wootten D , Furness S G B
Published: August 2013

The incidence of type 2 diabetes in developed countries is increasing yearly with a significant negative impact on patient quality of life and an enormous burden on the healthcare system. Current biguanide and thiazolidinedione treatments for type 2 diabetes have a number of clinical limitations, the most serious long‐term limitation being the eventual need for insulin replacement therapy (Table 1). Since 2007, drugs targeting the glucagon‐like peptide‐1 (GLP‐1) receptor have been marketed for the treatment of type 2 diabetes. These drugs have enjoyed a great deal of success even though our underlying understanding of the mechanisms for their pleiotropic effects remain poorly characterized even while major pharmaceutical companies actively pursue small molecule alternatives. Coupling of the GLP‐1 receptor to more than one signalling pathway (pleiotropic signalling) can result in ligand‐dependent signalling bias and for a peptide receptor such as the GLP‐1 receptor this can be exaggerated with the use of small molecule agonists. Better consideration of receptor signalling pleiotropy will be necessary for future drug development. This is particularly important given the recent failure of taspoglutide, the report of increased risk of pancreatitis associated with GLP‐1 mimetics and the observed clinical differences between liraglutide, exenatide and the newly developed long‐acting exenatide long acting release, albiglutide and dulaglutide.

Linked Articles

This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐5
Tetrahydrocannabinolic acid reduces nausea‐induced conditioned gaping in rats and vomiting in Suncus murinus
Authors: Rock E M , Kopstick R L , Limebeer C L , Parker L A
Published: August 2013

Background and Purpose

We evaluated the anti‐emetic and anti‐nausea properties of the acid precursor of Δ9‐tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models.

Experimental Approach

We investigated the effect of THCA on lithium chloride‐ (LiCl) induced conditioned gaping (nausea‐induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl‐induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 (CB1) receptor agonist‐like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist).

Key Results

In rats, THCA (0.05 and/or 0.5 mg·kg−1) suppressed LiCl‐induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5‐hydroxytryptamine‐1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg·kg−1) reduced LiCl‐induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg−1) did not suppress conditioned gaping to a LiCl‐paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non‐CB1 agonist‐like effects. THCA, but not THC was detected in plasma samples.

Conclusions and Implications

THCA potently reduced conditioned gaping in rats and vomiting in S. murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting.
Real‐time characterization of cannabinoid receptor 1 (CB1) allosteric modulators reveals novel mechanism of action
Authors: Cawston Erin E , Redmond William J , Breen Courtney M , Grimsey Natasha L , Connor Mark , Glass Michelle
Published: August 2013

Background and Purpose

The cannabinoid receptor type 1 (CB1) has an allosteric binding site. The drugs ORG27569 {5‐chloro‐3‐ethyl‐N‐[2‐[4‐(1‐piperidinyl)phenyl]ethyl]‐1H‐indole‐2‐carboxamide} and PSNCBAM‐1 {1‐(4‐chlorophenyl)‐3‐[3‐(6‐pyrrolidin‐1‐ylpyridin‐2‐yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(−)‐cis‐3‐[2‐hydroxy‐4‐(1,1‐dimethylheptyl)phenyl]‐trans‐4‐(3‐hydroxypropyl)cyclohexanol}, and studies have suggested that these allosteric modulators increase binding affinity but act as non‐competitive antagonists in functional assays. To gain a deeper understanding of allosteric modulation of CB1, we examined real‐time signalling and trafficking responses of the receptor in the presence of allosteric modulators.

Experimental Approach

Studies of CB1 signalling were carried out in HEK 293 and AtT20 cells expressing haemagglutinin‐tagged human and rat CB1. We measured real‐time accumulation of cAMP, activation and desensitization of potassium channel‐mediated cellular hyperpolarization and CB1 internalization.

Key Results

ORG27569 and PSNCBAM‐1 produce a complex, concentration and time‐dependent modulation of agonist‐mediated regulation of cAMP levels, as well as an increased rate of desensitization of CB1‐mediated cellular hyperpolarization and a decrease in agonist‐induced receptor internalization.

Conclusions and Implications

Contrary to previous studies characterizing allosteric modulators at CB1, this study suggests that the mechanism of action is not non‐competitive antagonism of signalling, but rather that enhanced binding results in an increased rate of receptor desensitization and reduced internalization, which results in time‐dependent modulation of cAMP signalling. The observed effect of the allosteric modulators is therefore dependent on the time frame over which the signalling response occurs. This finding may have important consequences for the potential therapeutic application of these compounds.
Endothelin‐1 and endothelin‐2 initiate and maintain contractile responses by different mechanisms in rat mesenteric and cerebral arteries
Authors: Compeer M G , Janssen G M J , De Mey J G R
Published: August 2013

Background and Purpose

Endothelin (ET)‐1 and ET‐2 cause potent long‐lasting vasoconstrictions by tight binding to smooth muscle ETA receptors. We tested the hypotheses that different mechanisms mediate initiation and maintenance of arterial contractile responses to ET‐1 and ET‐2 and that this differs among vascular beds.

Experimental Approach

Segments of rat mesenteric resistance artery (MRA) and basilar artery (BA) were studied in wire myographs with and without functional antagonists.

Key Results

Sensitivity and maximum of MRA contractile responses to ET‐1 were not, or only moderately, reduced by stimulation of soluble GC, AC or K+‐channels and by an inhibitor of receptor‐operated ion channels. However, each of these reduced maintenance of ET‐1 effects and relaxed ET‐1‐induced contractions in MRA. A calcium channel antagonist did not alter sensitivity, maximum and maintenance of ET‐1 effects, but relaxed ET‐1‐induced contractions in MRA. A PLC inhibitor prevented contractile responses to ET‐1 and ET‐2 in MRA and BA, and relaxed ET‐1‐ and ET‐2‐induced responses in MRA and ET‐1 effects in BA. A Rho‐kinase inhibitor did not modify sensitivity, maximum and maintenance of responses to both peptides in both arteries but relaxed ET‐2, but not ET‐1, effects in MRA and ET‐1 effects in BA.

Conclusions and Implications

PLC played a key role in arterial contractile responses to ETs, but ET‐1 and ET‐2 initiated and maintained vasoconstriction through different mechanisms, and these differed between MRA and BA. Selective functional antagonism may be considered for agonist‐ and vascular bed selective pharmacotherapy of ET‐related diseases.
Penta‐O‐galloyl‐β‐D‐glucose ameliorates inflammation by inhibiting MyD88/NF‐κB and MyD88/MAPK signalling pathways
Authors: Jang Se‐Eun , Hyam Supriya R , Jeong Jin‐Ju , Han Myung Joo , Kim Dong‐Hyun
Published: August 2013

Background and Purpose

The gallnut of Rhus chinensis MILL and its main constituent penta‐O‐galloyl‐β‐D‐glucose (PGG) inhibited NF‐κB activation in LPS‐stimulated peritoneal and colonic macrophages. Here we have investigated PGG mechanisms underlying anti‐inflammatory effects of PGG in vitro and in vivo.

Experimental Approach

Male C57BL/6 mice (18–22 g, 6 weeks old) were used to prepare peritoneal and colonic macrophages and for the induction of colitis by intrarectal administration of 2,3,4‐trinitrobenzene sulphonic acid (TNBS). A range of inflammatory markers and transcription factors were evaluated by elisa, immunoblotting, flow cytometry and confocal microscopy.

Key Results

Expression of Toll‐like receptor (TLR)‐4 or Lipopolysaccharide (LPS) binding to TLR‐4 in LPS‐stimulated peritoneal macrophages was not affected by PGG. However PGG inhibited binding of an anti‐MyD88 antibody to peritoneal macrophages, but did not reduce binding of anti–IL‐1 receptor‐associated kinase (IRAK1) and IRAK4 antibodies to the macrophages with or without transfection with MyD88 siRNA. PGG potently reduced the activation of IRAK1, NF‐κB, and MAPKs in LPS‐ or pepetidoglycan‐stimulated peritoneal and colonic macrophages. PGG suppressed IL‐1β, TNF‐α and IL‐6 in LPS‐stimulated peritoneal macrophages, while increasing expression of the anti‐inflammatorycytokine IL‐10. Oral administration of PGG inhibited colon shortening and myeloperoxidase activity in mice with TNBS‐induced colitis, along with reducing NF‐κB activation and IL‐1β, TNF‐α, and IL‐6 levels, whereas it increased IL‐10.

Conclusions and Implications

PGG reduced activation of NF‐κB and MAPK signalling pathways by directly interacting with the MyD88 adaptor protein. PGG may ameliorate inflammatory diseases such as colitis.
Retraction techniques in laparoscopic colorectal surgery: a literature‐based review
Authors: Ladwa N. , Sajid M. S. , Pankhania N. K. , Sains P. , Baig M. K.
Published: August 2013

Aim

To systematically review the published literature and describe the various techniques of bowel and mesentery retraction available for use in laparoscopic colorectal resection.

Method

A comprehensive search of the literature was undertaken using MESH terms ‘retraction’, ‘laparoscopic’ and ‘colorectal’. All articles describing methods of retraction in laparoscopic colorectal surgery were included.

Results

Twelve methods of retraction in laparoscopic colorectal surgery were described. Five case‐based series and three case studies were reported on 108 patients. Techniques were classified into those offering retraction of the small or large bowel or according to the mode of retraction.

Conclusion

Many retraction methods are available to the surgeon varying in cost, invasiveness and complexity. Adequate retraction remains a challenge for optimal exposure and dissection during laparoscopic colorectal surgery.
Early postoperative complications after stapled vs handsewn restorative proctocolectomy with ileal pouch‐anal anastomosis in 148 patients with familial adenomatous polyposis coli: a matched‐pair analysis
Authors: Ganschow P. , Warth R. , Hinz U. , Büchler M. W. , Kadmon M.
Published: August 2013

Aim

Restorative proctocolectomy with ileal pouch‐anal anastomosis for patients with familial adenomatous polyposis (FAP) and ulcerative colitis (UC) has been modified from a transanal hand‐suture after mucosectomy to a stapled ileal pouch‐anal anastomosis (IPAA) without mucosectomy. Better functional results favour stapled anastomosis; however, stapled anastomosis results in higher rates of adenomas in persisting anorectal mucosa. The purpose of this study was to compare the two techniques of pouch‐anal anastomosis with respect to early postoperative complications in a collective of FAP patients.

Method

The study was performed as a matched‐pair analysis. Data were obtained from a prospectively collected database.

Results

The overall rate of postoperative complications was higher after stapled IPAA (31% stapled vs 23% handsewn), with anastomotic stricture occurring in 24.3% (stapled) and 16.2% (handsewn) (P = 0.22). Any leakage or pelvic abscess formation after stapled anastomosis occurred within 30 days in almost all patients, whereas these were mainly diagnosed between 30 days and 6 months after handsewn IPAA. A laparoscopic approach was used in 56.7% of patients in the stapled group but in only two patients in the handsewn group. Intra‐operative blood loss was significantly higher in the handsewn group (mean ± SD: 699 ± 511 ml vs 369 ± 343 ml; P < 0.0001), as was the volume of blood transfused (mean ± SD: 205 ± 365 ml vs 8 ± 49 ml; P < 0.0001). Function did not differ between the groups.

Conclusion

There was a nonstatistically significant tendency towards a higher rate of early postoperative complications after stapled IPAA. The timing of anastomotic leakage and abscess formation differed between the groups.
Non‐traded Goods, Globalization and Union Influence
Authors: Kreickemeier Udo , Meland Frode
Published: August 2013

We study how globalization affects sector‐specific wages, employment levels and welfare in a model of general oligopolistic equilibrium with partly unionized labour markets. Globalization is modelled as either reducing trade costs in open sectors or opening up shielded sectors to trade. Both forms of globalization increase union coverage and lead to lower union wage premia in shielded sectors. Trade cost reductions furthermore lead to higher union wage premia in open sectors and to lower aggregate welfare, while an increased number of open sectors lowers the union wage premium in open sectors, and may increase welfare.
Immune regulation of bone loss by Th17 cells in oestrogen‐deficient osteoporosis
Authors: Zhao Renqing
Published: August 2013

Background

The role of T helper (Th) 17 cells in autoimmune diseases has been extensively studied recently, but its function in oestrogen‐deficient osteoporosis remains undefined. This review aimed to explore the role of Th17 cells in regulating bone loss induced by oestrogen deficiency.

Materials and methods

We searched PubMed, Embase, Google Scholar and Biosis up to 1 February 2013 for immune regulation of oestrogen‐deficient osteoporosis by Th17 cells. Terms relevant to immunity, oestrogen deficiency, osteoporosis and Th17 cells were used for database searching. Seventy‐five papers met the predetermined searching criteria.

Results

Studies indicate Th17 lineage to be a potent osteoclastogenic mediator in oestrogen‐deficient osteoporosis. Oestrogen deficiency promotes osteoclastogenesis by up‐regulating Th17 cell populations in bone marrow and IL‐17 levels in peripheral blood. Meanwhile, transcription factors involved in Th17 cell differentiation, such as RORγt and RORα, are highly expressed in ovariectomized animals. Treatment with IL‐17 significantly promotes production of RANKL, TNF and IL‐6 as well as TRAP+ cells in culture; blocking IL‐17 pathway significantly reduces abundance of Th17 cells and effectively prevents bone loss in ovariectomized mice.

Conclusions

The main body of literatures suggests Th17 to be a critical modulator in the pathogenesis of oestrogen‐deficient osteoporosis, which supports the notion that oestrogen‐deficient osteoporosis is a complex interplay between oestrogen, osteoclastogenic cytokines and osteoclasts. In addition, therapeutic strategies targeting IL‐17 networks may be clinically useful in treatment for postmenopausal osteoporosis.
Surgical management and long‐term seizure outcome after epilepsy surgery for different types of epilepsy associated with cerebral cavernous malformations
Authors: von der Brelie Christian , Malter Michael P. , Niehusmann Pitt , Elger Christian E. , von Lehe Marec , Schramm Johannes
Published: August 2013

Purpose

Precise outcome data about the surgical therapy of cerebral cavernous malformation (CCM)–associated epilepsy is scarce regarding different epilepsy types, surgical approach, and outcome. Long‐term outcome in patients with CCM‐associated epilepsy is analyzed in a large single‐center series.

Methods

Seizure outcome data >24 months was available in 118 patients. The influence of different parameters of preoperative workup and surgical technique was analyzed with regard to seizure outcome.

Key Findings

The study cohort comprised 76 patients with drug‐resistant epilepsy (DRE), 20 patients with chronic epilepsy that did not meet the definition of DRE, as well as 22 patients with sporadic seizures. Temporal localization of CCMs predisposed to develop DRE. Detailed epileptologic workup was performed in 85 patients; invasive monitoring was done in 23 (37%) of 76 DRE cases. In 84% of DRE cases more extensive resections were performed. Mean follow‐up varied between 107 and 137 months for the three groups. Seizure freedom in DRE was 88%, in chronic epilepsy 80%, and in sporadic seizures was 91%. Longer symptom duration was associated with worse seizure outcome. Outcome of patients who underwent invasive monitoring was not worse. The outcome in CCM‐associated DRE can be good if more extensive resections are used and if noninvasive and/or invasive presurgical epileptologic workup is used whenever indicated. DRE was considerably more frequent in the temporal lobe, suggesting that temporal localization predisposes development of DRE. Seizure freedom rates were stable over a long period.

Significance

Surgical therapy of CCM‐associated seizures and epilepsy can be successful if different surgical techniques according to presurgical evaluation are realized. To prevent clinical worsening into DRE, surgical intervention in CCM‐associated epilepsy may be considered early.
Competing influence of vacancies and interstitial atoms on temperature dependence of creep under irradiation
Authors: Selyshchev P. , Sugakov V.
Published: August 2013

In the framework of the Orowan model, a theoretical approach is developed to explain the appearance of a break (local minimum and maximum) on a curve of creep rate dependence on temperature of materials under irradiation. The break is explained by competition of radiation and thermal defect fluxes to dislocations. At some temperature, the fluxes of interstitial atoms and vacancies become equal and compensate each other. Thus, the dislocations do not climb. Climb–glide mechanism does not contribute to the creep and the creep decreases. It is shown that the presence of sinks with different preference coefficients is necessary for the appearance of the break. Theoretical and experimental results are in good agreement.
Coralline algal structure is more sensitive to rate, rather than the magnitude, of ocean acidification
Authors: Kamenos Nicholas A. , Burdett Heidi L. , Aloisio Elena , Findlay Helen S. , Martin Sophie , Longbone Charlotte , Dunn Jonathan , Widdicombe Stephen , Calosi Piero
Published: August 2013

Marine pCO2 enrichment via ocean acidification (OA), upwelling and release from carbon capture and storage (CCS) facilities is projected to have devastating impacts on marine biomineralisers and the services they provide. However, empirical studies using stable endpoint pCO2 concentrations find species exhibit variable biological and geochemical responses rather than the expected negative patterns. In addition, the carbonate chemistry of many marine systems is now being observed to be more variable than previously thought. To underpin more robust projections of future OA impacts on marine biomineralisers and their role in ecosystem service provision, we investigate coralline algal responses to realistically variable scenarios of marine pCO2 enrichment. Coralline algae are important in ecosystem function; providing habitats and nursery areas, hosting high biodiversity, stabilizing reef structures and contributing to the carbon cycle. Red coralline marine algae were exposed for 80 days to one of three pH treatments: (i) current pH (control); (ii) low pH (7.7) representing OA change; and (iii) an abrupt drop to low pH (7.7) representing the higher rates of pH change observed at natural vent systems, in areas of upwelling and during CCS releases. We demonstrate that red coralline algae respond differently to the rate and the magnitude of pH change induced by pCO2 enrichment. At low pH, coralline algae survived by increasing their calcification rates. However, when the change to low pH occurred at a fast rate we detected, using Raman spectroscopy, weaknesses in the calcite skeleton, with evidence of dissolution and molecular positional disorder. This suggests that, while coralline algae will continue to calcify, they may be structurally weakened, putting at risk the ecosystem services they provide. Notwithstanding evolutionary adaptation, the ability of coralline algae to cope with OA may thus be determined primarily by the rate, rather than magnitude, at which pCO2 enrichment occurs.
Relationship between Geriatric Nutritional Risk Index and total lymphocyte count and mortality of hemodialysis patients
Authors: Jung Yeon Soon , You Gain , Shin Ho Sik , Rim Hark
Published: August 2013

We examined the relationships between Geriatric Nutritional Risk Index (GNRI), total lymphocyte count (TLC), and mortality in hemodialysis (HD) patients. We examined GNRI and TLC in 120 maintenance HD patients and followed these patients for 120 months. Predictors of all‐cause death were examined using life table analysis and the Cox proportional hazards model. TLC marginally correlated with GNRI (r = 0.176; p = 0.090) and significantly with phosphorus levels (r = 0.206; p = 0.026). Life table analysis revealed that subjects with a GNRI < 90 (n = 19) had lower survival rates than did those with a GNRI ≥ 90 (n = 101; Wilcoxon's test, p = 0.048), but subjects with a TLC < 1500/mm3 (n = 76) had similar survival rates compared with subjects with a TLC ≥ 1500/mm3 (n = 44; Wilcoxon's test, p = 0.500). Multivariate Cox proportional hazards analyses demonstrated that GNRI is a significant predictor of mortality (hazard ratio 9.315, 95% confidence interval 1.161–74.753, p = 0.036), after adjusting for age, sex, presence of type 2 diabetes mellitus, Kt/V, normalized protein catabolic rate, hematocrit, phosphorus, systolic blood pressure and TLC. Our findings suggest the TLC may be used as a simple nutritional tool, but may not be a predictor of mortality in HD patients. These findings require confirmation by further studies.
Hybrid Atlantics: Future Directions for the History of the Atlantic World
Authors: Cañizares‐Esguerra Jorge , Breen Benjamin
Published: August 2013

Fundamental features of the early modern Atlantic – like the slave trade, the rise of experimental science and long‐distance commerce, and the proliferation of religious confessions – were transnational in character. This essay surveys recent work in the field, emphasizing emerging scholarship on the hybrid nature of the Atlantic world. Yet for hybridity to work as a useful analytical category, we need to do away with the narrative of “Northwestern Europeanization” as the normative model. We explore how ecology and place, science and medicine, and diasporic or extra‐national groups like smugglers, Jews, and slaves helped create an Atlantic that was defined more by its cross‐cultural encounters, local contexts, and mixed identities than by the power of European states.
Historiographic Foodways: A Survey of Food and Drink Histories in Australia
Authors: Luckins Tanja
Published: August 2013

This essay is a survey of the field of food and drink history in Australia since the 1970s. It discusses the range of research and picks out key historiographic aspects: the search for an Australian cuisine; regional food cultures; connection between sources and historical interpretation; and the interdisciplinarity of food and drink history. It suggests that as food and drink histories have broadened beyond a search for culinary traditions and a gastronomic sensibility, so our understanding of food and drink in Australian history has deepened. It also argues that food and drink history is more than textual knowledge in books and articles: television programs and exhibitions held in museums and libraries, for example, have enhanced our understanding of food and drink histories.
Learning for lower energy consumption
Authors: Isaksson Charlotta
Published: August 2013

Energy‐efficient technologies are not just objects that might enable households to carry out more sustainable practices; they are tools, and using them effectively requires certain skills and knowledge. Households' difficulties in handling home heating and hot water technologies in particular have been highlighted as an obstacle to meeting energy conservation objectives. This has given rise to calls for improved support based on how the households define their activities and handle these technologies. By deploying a socio‐cultural theory of learning and using in‐depth interviews with households that have recently purchased renewable heating systems, this paper examines various situations in which people have learnt to use the technologies, and it discusses lessons learnt that may be useful for developing support. The results demonstrate three common learning approaches and identify situations where the learning process runs smoothly and where it does not. The conclusions suggest strategies for helping households overcome the resistance embedded in the interaction with the technologies, and they highlight the importance, when developing support, of starting with what creates meaning in various situations.
Empty iron stores in children and young adults—the diagnostic accuracy of MCV, MCH, and MCHC
Authors: Åsberg A. E. , Mikkelsen G. , Aune M. W. , Åsberg A.
Published: August 2013

Introduction

Erythrocyte mean cell volume (MCV) is used clinically to classify anemia, and normal values may be used to exclude iron deficiency. We have studied the diagnostic accuracy of MCV and the related measures mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) in diagnosing empty iron stores in children and young adults.

Methods

Diagnostic accuracy of MCV, MCH, and MCHC was studied by ROC curve analysis in 6443 ambulant patients aged 0.5–25 years, of which 476 were anemic. In all patients, blood hemoglobin, MCV, MCH, and serum ferritin were measured in specimens sampled at the same time. MCHC was calculated as MCH divided by MCV. The gold standard of empty iron stores was s‐ferritin <10, 15, or 20 μg/L. The cutoff limit of MCV giving 90% sensitivity in diagnosing serum ferritin <15 μg/L was constructed using quantile regression.

Results

Generally, MCH was slightly more accurate than MCV and MCHC. In the whole study population, the area under the ROC curve was 0.68–0.93 for MCV, 0.73–0.96 for MCH, and 0.68–0.87 for MCHC; and 0.70–0.86, 0.71–0.89, and 0.68–0.88, respectively, in the anemic subpopulation. At the cutoff limits of MCV giving a sensitivity of 90% at all ages in anemic patients, the specificity was about 50%.

Conclusion

Mean cell hemoglobin, MCH, and MCHC are only moderately accurate in diagnosing empty iron stores in children and young adults, and normal values of these tests do not exclude empty iron stores in anemic patients.
Physician Migration in the Global South between Cuba and South Africa
Authors: Hammett Daniel
Published: August 2013

Transnational physician migration has concerned states' health and migration policies for many years. Recent developments have increased attention to the outcomes of these flows in the global south, where physician emigration is undermining public health policies. Cuba's exporting of medical professionals presents an alternative dynamic, based upon both an ideology of humanitarian solidarity and a need to secure hard currency earnings. The benefits and challenges arising from a bilateral agreement between Cuba and South Africa to supply Cuban doctors to South Africa and training at the Latin American Medical School (ELAM) for South African medical students are addressed. The benefits of skills enhancement and professional development are noted, as well as the economic benefits for both the Cuban government and individual doctors, while concerns with the appropriateness of the medical training provided at ELAM for the South African health context and the sustainability of the current policy are discussed.

Policy Implications

Strategic bi‐lateral agreements offer a productive route towards more sustainable management of skilled migration.

When migration agreements include skills training, attention is needed to ensure the training provided is appropriate to the destination context: attention needs to be paid to the appropriateness of the medical training afforded to South African medical students in Cuba for health requirements in South Africa.

International migration agreements can form part of a broader policy suite aimed at realizing public health and other development priorities. However, attention must be paid to the suitability and sustainability of the outcomes of these practices.