bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia without Walls: reflections on the Joseph Rowntree Foundation programme
Authors: Hare Philly
Published: August 2016

Purpose

The purpose of this paper is to describe the key elements of a major work programme on dementia, and to reflect on the practical learning derived.

Design/methodology/approach

The paper describes the whole range of programme activity, including research projects, think-pieces, action research, demonstrations, evaluations and production of resources such as films, infographics, case studies, practice guides and positive image galleries.

Findings

The active, meaningful engagement of people with dementia and their families is fundamental. Communities must engage with, and achieve equity for, all people with dementia, whatever their circumstances. Practical barriers to inclusion must be addressed if normal lives are to be continued. The human rights of people with dementia and carers must be recognised and promoted. Local grassroots community activity is the bedrock of dementia friendly communities – but this activity must be supported by strong strategic planning, commissioning and leadership. There is no template – each community must develop its own approach.

Practical implications

The paper highlights many examples of good practice which can inform the work of commissioners and practitioners, as well as wider communities. These focus particularly on good practice in engagement and involvement; and the co-production of dementia friendly communities with people with dementia.

Social implications

The programme highlights the importance of social barriers to the inclusion of people with dementia in their communities, and gives examples of communities which have tried to overcome these through attitudinal and environmental change.

Originality/value

Joseph Rowntree Foundation’s programme is highly innovative and well-regarded.
Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T‐cell lymphomas
Authors: Hamada Toshihisa , Sugaya Makoto , Tokura Yoshiki , Ohtsuka Mikio , Tsuboi Ryoji , Nagatani Tetsuo , Tani Mamori , Setoyama Mitsuru , Matsushita Shigeto , Kawai Kazuhiro , Yonekura Kentaro , Yoshida Tsuyoshi , Saida Toshiaki , Iwatsuki Keiji
Published: August 2016

Safety, tolerability, pharmacokinetics and efficacy of bexarotene, a novel retinoid X receptor (RXR)‐selective retinoid, were evaluated in Japanese patients with stage IIB–IVB and relapsed/refractory stage IB–IIA cutaneous T‐cell lymphomas (CTCL). This study was conducted as a multicenter, open‐label, historically controlled, single‐arm phase I/II study. Bexarotene was p.o. administrated once daily at a dose of 300 mg/m2 for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m2 in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m2 met the response criteria using the modified severity‐weighted assessment tool (mSWAT) at 24 weeks or discontinuation. Dose‐limiting toxic effects (DLT) were present in four of 13 patients (31%) at a dose of 300 mg/m2: two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m2 bexarotene. In the 13 patients at 300 mg/m2, common drug‐related adverse events (AE) included hypothyroidism (92%), hypercholesterolemia (77%), leukopenia or neutropenia (39%), nasopharyngitis or anemia (31%). The treatment‐related grade 3 AE included hypertriglyceridemia (4/16 patients, 25%), increased alanine aminotransferase, increased aspartate aminotransferase, dyslipidaemia, leukopenia and neutropenia (1/16 patients, 6%), and one of 16 patients experienced grade 4 hypertriglyceridemia. No patients discontinued bexarotene due to the AE during the study, but dose reduction or suspension was required. Bexarotene was shown to be well tolerated at 300 mg/m2 once daily and effective in Japanese patients with CTCL.
Fluid injection monitoring using electrical resistivity tomography — five years of injection at Ketzin, Germany
Authors: Bergmann P. , Schmidt‐Hattenberger C. , Labitzke T. , Wagner F.M. , Just A. , Flechsig C. , Rippe D.
Published: August 2016

Between the years 2008 and 2013, approximately 67 kilotons of CO2 have been injected at the Ketzin site, Germany. As part of the geophysical monitoring programme, time‐lapse electrical resistivity tomography has been applied using crosshole and surface‐downhole measurements of electrical resistivity tomography. The data collection of electrical resistivity tomography is partly based on electrodes that are permanently installed in three wells at the site (one injection well and two observation wells). Both types of ERT measurements consistently show the build‐up of a CO2‐related resistivity signature near the injection point. Based on the imaged resistivity changes and a petrophysical model, CO2 saturation levels are estimated. These CO2 saturations are interpreted in conjunction with CO2 saturations inferred from neutron‐gamma loggings. Apart from the CO2–brine substitution response in the observed resistivity changes, significant imprints from the dynamic behaviour of the CO2 in the reservoir are observed.
Hydrogen peroxide scavenger, catalase, alleviates ion transport dysfunction in murine colitis
Authors: Barrett Kim E , McCole Declan F
Published: August 2016

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) contribute to epithelial damage and ion transport dysfunction (key events in inflammatory diarrhoea) in inflammatory bowel disease (IBD). The aim of this study was to identify if H2O2 mediates suppression of colonic ion transport function in the murine dextran sulfate sodium (DSS) colitis model by using the H2O2 degrading enzyme, catalase. Colitis was induced by administering DSS (4%) in drinking water for 5 days followed by 3 days on normal H2O. Mice were administered either pegylated catalase or saline at day −1, 0 and +1 of DSS treatment. Ion transport responses to the Ca2+‐dependent agonist, carbachol (CCh), or the cAMP‐dependent agonist, forskolin, were measured across distal colonic mucosa mounted in Ussing chambers. Parameters of DSS‐induced inflammation (loss in body weight, decreased colon length, altered stool consistency), were only partially alleviated by catalase while histology was only minimally improved. However, catalase significantly reversed the DSS‐induced reduction in baseline ion transport as well as colonic Isc responses to CCh. However, ion transport responses to forskolin were not significantly restored. Catalase also reduced activation of ERK MAP kinase in the setting of colitis, and increased expression of the Na+‐K+‐2Cl− cotransporter, NKCC1, consistent with restoration of ion transport function. Ex vivo treatment of inflamed colonic mucosae with catalase also partially restored ion transport function. Therefore, catalase partially prevents, and rescues, the loss of ion transport properties in DSS colitis even in the setting of unresolved tissue inflammation. These findings indicate a prominent role for ROS in ion transport dysfunction in colitis and may suggest novel strategies for the treatment of inflammatory diarrhoea.
Inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity suppresses microglia‐mediated inflammatory responses
Authors: Zhang Yu , Gu Ruinan , Jia Jia , Hou Tingjun , Zheng Long Tai , Zhen Xuechu
Published: August 2016

Macrophage migration inhibitory factor (MIF), a pleiotropic pro‐inflammatory cytokine, is a key regulator in both innate and acquired immunity systems. MIF has become a promising drug target for inflammatory diseases. Apart from its cytokine activities, MIF is known to act as a d‐dopachrome tautomerase. Our previous work has identified that 3‐[(biphenyl‐4‐ylcarbonyl)carbamothioyl]amino benzoic acid (Z‐590) exhibited a potent inhibitory activity against MIF. In this study, we investigate the effect of Z‐590 on lipopolysaccharide (LPS)‐activated microglial cell activation. Our results demonstrate that Z‐590 significantly decreases the production of nitric oxide (NO), tumour necrosis factor‐alpha (TNF‐α), interleukin (IL)‐6, IL‐1β, cyclooxygenase (COX‐2), inducible nitric oxide synthase (iNOS) as well as reactive oxygen species (ROS) involved in inhibiting MAKPs signalling pathway in LPS‐stimulated microglia cells. Furthermore, Z‐590 reduced cytotoxicity of activated microglia toward HT‐22 hippocampal cells in a microglia‐conditioned medium system. Taken together, these results indicate that MIF inhibitor Z‐590 elicits a potent inhibitor for microglia‐mediated neuroinflammation.
Host resistance enhances susceptibility of Callosobruchus maculatus (Coleoptera: Chrysomelidae) to herbal extract of Echinophora platyloba
Authors: Tabadkani Seyed Mohammad , Khoobdel Mehdi , Tavakoli Hamid Reza
Published: August 2016

It has been argued that resistant cultivars may enhance the susceptibility of insect pests to insecticides, and thus can reduce crop production costs by lowering the rate of insecticide application. Here we studied the susceptibility of the cowpea seed beetle, Callosobruchus maculatus (Coleoptera: Chrysomelidae), reared on either a susceptible or resistant cultivar of the mung bean (Vigna radiate), to a herbal extract taken from the prickly parsnip, Echinophora platyloba (Umbelliferae). After selection of a susceptible (Parto) and a resistant (Sahar) cultivar, the median lethal concentration (LC50) of the herbal extract was determined as 24.41 and 20.28 μL/250 mL air against beetles reared on susceptible and resistant cultivars, respectively. Rearing on resistant cultivar had a significant effect on biological parameters of C. maculatus regardless of insecticide application. However, herbal extract showed a significant interaction with host resistance in terms of oviposition rate and pre‐adult development time. These results provide evidence that the resistant cultivar increases the susceptibility of C. maculatus to herbal extract. The use of plant resistance in combination with narrow‐spectrum insecticides seems to be of both economic and environmental importance, as it can reduce the costs of crop production and lower the doses of insecticides required for satisfactory pest control.
Allopurinol therapy improves vascular endothelial function in subjects at risk for cardiovascular diseases: a meta‐analysis of randomized controlled trials
Authors: Xin Wei , Mi Shuhua , Lin Zhiqin
Published: August 2016

Aims

The effect of allopurinol on flow‐mediated dilation (FMD), an index of endothelial function in humans, remains inconsistent. We performed a meta‐analysis to determine whether allopurinol therapy could improve FMD.

Methods

Human intervention studies were identified by systematic searches of Medline, Embase, Cochrane's library, and references of related reviews and studies. A random‐effect model was applied to estimate the pooled results.

Results

Ten randomized controlled trials with 594 subjects at risk of cardiovascular risks were included. Results of the meta‐analysis indicated that allopurinol therapy significantly improved FMD in these subjects as compared with control groups (WMD=1.67%, 95% CI: 0.83% ~ 2.50%, P<.001; I2=86%), with no evidence of significant heterogeneity if only double‐blinded studies were included (WMD=1.36%, 95% CI: 0.89% ~ 1.83%, P<.001; I2=21%). Results of metaregression and subgroup analyses suggested that the benefit of allopurinol to FMD seemed to be not related to its uric acid (UA)‐lowering action. Moreover, allopurinol therapy may be associated with more remarkable improvement of FMD in subjects with lower serum UA (<7 mg/dL: WMD=2.62%, 95% CI: 1.10% ~ 4.14%), compared to those with higher UA (≥7 mg/dL: WMD=0.87%, 95% CI: 0.37% ~ 1.38%; P for subgroup difference=.03).

Conclusions

Allopurinol therapy is associated with significantly improved endothelial function in subjects at risk of CVD risks, and the beneficial effects of allopurinol seemed to be more remarkable in patients with normal UA at baseline.
Performance in real life of the European Network on Drug Allergy algorithm in immediate reactions to beta‐lactam antibiotics
Authors: Moreno E. , Laffond E. , Muñoz‐Bellido F. , Gracia M. T. , Macías E. , Moreno A. , Dávila I.
Published: August 2016

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta‐lactam (BL) allergy. We evaluated its performance in real life. During 1994–2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDA's short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re‐evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present.
Reduced occurrence of severe visual impairment after introduction of anti‐Vascular Endothelial Growth Factor in wet age‐related macular degeneration – a population‐ and register‐based study from northern Sweden
Authors: Granstam Elisabet , Westborg Inger , Barkander Anna , Börjesson Malin , Lindahl Sara , Meszaros Eva , Wojciechowska‐Zajac Anna , Wagner Philippe , Albrecht Susanne , Karlsson Niklas , Bjärnhall Gunilla , Lövestam‐Adrian Monica
Published: August 2016

Purpose

To study the occurrence of severe visual impairment (SVI) and treatment outcome at 12 months in patients treated for wet age‐related macular degeneration (AMD) by use of data from the Swedish Macula Register (SMR) and referrals to the regional low vision clinics in five northern counties.

Methods

Referrals to low vision clinics during 2005, 2009 and 2013 and treatment outcome at 12 months from the SMR database from 2008 until 2013 in patients >65 years of age in five northern counties were included in the survey.

Results

The rate of referral due to AMD was significantly reduced during the time period (−48%; p < 0.001). At 12 months, a significant slight mean improvement in logMAR visual acuity (VA) was observed (−0.01, SD 0.37; p < 0.001) after a mean of 5.0 ± 2.3 anti‐vascular endothelial growth factor (VEGF)‐injections were administered. Age and low baseline VA was associated with less favourable visual outcome (p < 0.001).

Conclusion

Referral rate to low vision clinic is a valuable tool for estimating occurrence of SVI and fell between the years 2005 until 2013. Data from the SMR showed improvement in visual acuity on the whole, but also identified patients at high risk for developing SVI during anti‐VEGF‐treatment.
Extended‐spectrum β‐lactamase‐producing bacteria caused less than 5% of urinary tract infections in a paediatric emergency centre
Authors: Jacmel Lisa , Timsit Sandra , Ferroni Agnès , Auregan Clémentine , Angoulvant François , Chéron Gérard
Published: August 2016

Aim

The last decade has seen a significant increase in extended‐spectrum β‐lactamase (ESBL) secreting organisms responsible for paediatric urinary tract infections (UTIs), particularly in community‐acquired infections. These expose patients to the risks of antibiotic treatment failure and renal scarring. This prospective study examined the prevalence and risk factors of febrile ESBL UTIs and their treatment in the paediatric emergency department of a university hospital.

Methods

In this prospective observational study, all children from 0 to 16 years of age with febrile UTIs were included from May 2012 to April 2013. Cases with and without ESBL involvement were compared.

Results

Of the 474 diagnosed febrile UTIs, 22 (4.6%) with a 95% confidence interval (95% CI) of 2.9–6.9 were due to an ESBL‐producing organism. Escherichia coli was found in 85% of cases. Significant odds ratios (OR) for ESBL urinary tract infections were prior hospitalisation (OR 4.1, 95% CI 1.6–10.8), urinary tract abnormalities (OR 3.9, 95% CI 1.5–10.2) and previous antibiotic treatment (OR 3.1, 95% CI 1.2–8.8). All ESBL urinary tract infections had positive outcomes.

Conclusion

The prevalence of febrile ESBL urinary tract infections was less than 5% in a paediatric emergency department. This low rate was not high enough to justify changing our guidelines.
Insight towards the identification of cytosolic Ca2+‐binding sites in ryanodine receptors from skeletal and cardiac muscle
Authors: Gaburjakova M. , Gaburjakova J.
Published: August 2016

Ca2+ plays a critical role in several processes involved in skeletal and cardiac muscle contraction. One key step in cardiac excitation–contraction (E–C) coupling is the activation of the cardiac ryanodine receptor (RYR2) by cytosolic Ca2+ elevations. Although this process is not critical for skeletal E–C coupling, the activation and inhibition of the skeletal ryanodine receptor (RYR1) seem to be important for overall muscle function. The RYR1 and RYR2 channels fall within the large category of Ca2+‐binding proteins that harbour highly selective Ca2+ ‐binding sites to receive and translate the various Ca2+ signals into specific functional responses. However, little is known about the precise localization of these sites within the cytosolic assembly of both RYR isoforms, although several experimental lines of evidence have highlighted their EF‐hand nature. EF‐hand proteins share a common helix‐loop‐helix structural motif with highly conserved residues involved in Ca2+ coordination. The first step in predicting EF‐hand positive regions is to compare the primary protein structure with the EF‐hand motif by employing available bioinformatics tools. Although this simple method narrows down search regions, it does not provide solid evidence regarding which regions bind Ca2+ in both RYR isoforms. In this review, we seek to highlight the key findings and experimental approaches that should strengthen our future efforts to identify the cytosolic Ca2+‐binding sites responsible for activation and inhibition in the RYR1 channel, as much less work has been conducted on the RYR2 channel.
Cross‐Cultural Differences in Applicant Faking on Personality Tests: A 43‐Nation Study
Authors: Fell Clemens B. , König Cornelius J.
Published: August 2016

In a globalised world, more and more organisations have to select from pools of applicants from different cultures, often by using personality tests. If applicants from different cultures were to differ in the amount of faking on personality tests, this could threaten their validity: Applicants who engage in faking will have an advantage, and will put those who do not fake at a disadvantage. This is the first study to systematically examine and explain cross‐cultural differences in actual faking behavior. In N = 3,678 employees from 43 countries, a scenario‐based repeated measures design (faking vs. honest condition) was applied. Results showed that faking differed significantly across countries, and that it was systematically related to countries’ cultural characteristics (e.g. GLOBE's uncertainty avoidance, future orientation, humane orientation, and in‐group collectivism), but in an unexpected way. The study discusses these findings and their implications for research and practitioners.
Tumor cells with neuronal intermediate progenitor features define a subgroup of 1p/19q co‐deleted anaplastic gliomas
Authors: Bielle Franck , Ducray François , Mokhtari Karima , Dehais Caroline , Adle‐Biassette Homa , Carpentier Catherine , Chanut Anaïs , Polivka Marc , Poggioli Sylvie , Rosenberg Shai , Giry Marine , Marie Yannick , Duyckaerts Charles , Sanson Marc , Figarella‐Branger Dominique , Idbaih Ahmed ,   Pola Network
Published: August 2016

The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co‐deleted, grade III (O3id) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage‐oriented, heterogeneity in O3id. Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3id overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3id is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3id recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3id and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3id. A better understanding of spatial and temporal intratumor cell heterogeneity in O3id will open new therapeutic avenues overcoming resistance to current antitumor treatments.
Impact of normal faulting and pre‐rift salt tectonics on the structural style of salt‐influenced rifts: the Late Jurassic Norwegian Central Graben, North Sea
Authors: Ge Zhiyuan , Gawthorpe Rob L. , Rotevatn Atle , Thomas Michel Bøgh
Published: August 2016

Studies of salt‐influenced rift basins have focused on individual or basin‐scale fault system and/or salt‐related structure. In contrast, the large‐scale rift structure, namely rift segments and rift accommodation zones and the role of pre‐rift tectonics in controlling structural style and syn‐rift basin evolution have received less attention. The Norwegian Central Graben, comprises a complex network of sub‐salt normal faults and pre‐rift salt‐related structures that together influenced the structural style and evolution of the Late Jurassic rift. Beneath the halite‐rich, Permian Zechstein Supergroup, the rift can be divided into two major rift segments, each comprising rift margin and rift axis domains, separated by a rift‐wide accommodation zone – the Steinbit Accommodation Zone. Sub‐salt normal faults in the rift segments are generally larger, in terms of fault throw, length and spacing, than those in the accommodation zone. The pre‐rift structure varies laterally from sheet‐like units, with limited salt tectonics, through domains characterised by isolated salt diapirs, to a network of elongate salt walls with intervening minibasins. Analysis of the interactions between the sub‐salt normal fault network and the pre‐rift salt‐related structures reveals six types of syn‐rift depocentres. Increasing the throw and spacing of sub‐salt normal faults from rift segment to rift accommodation zone generally leads to simpler half‐graben geometries and an increase in the size and thickness of syn‐rift depocentres. In contrast, more complex pre‐rift salt tectonics increases the mechanical heterogeneity of the pre‐rift, leading to increased complexity of structural style. Along the rift margin, syn‐rift depocentres occur as interpods above salt walls and are generally unrelated to the relatively minor sub‐salt normal faults in this structural domain. Along the rift axis, deformation associated with large sub‐salt normal faults created coupled and decoupled supra‐salt faults. Tilting of the hanging wall associated with growth of the large normal faults along the rift axis also promoted a thin‐skinned, gravity‐driven deformation leading to a range of extensional and compressional structures affecting the syn‐rift interval. The Steinbit Accommodation Zone contains rift‐related structural styles that encompass elements seen along both the rift margin and axis. The wide variability in structural style and evolution of syn‐rift depocentres recognised in this study has implications for the geomorphological evolution of rifts, sediment routing systems and stratigraphic evolution in rifts that contain pre‐rift salt units.
Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties
Authors: Waszkielewicz Anna M. , Słoczyńska Karolina , Pękala Elżbieta , Żmudzki Paweł , Siwek Agata , Gryboś Anna , Marona Henryk
Published: August 2016

A series of new xanthone derivatives have been synthesized and evaluated for their anticonvulsant properties in the maximal electroshock, subcutaneous metrazole tests and for neurotoxicity in the rotarod in mice, i.p. and rats, p.o. Compound 9: R,S‐2‐{2‐[(1‐hydroxybutan‐2‐yl]amino)ethoxy}‐9H‐xanthen‐9‐one and compound 12: R,S‐2‐{3‐[(1‐hydroxybutan‐2‐yl)amino]propoxy}‐9H‐xanthen‐9‐one exerted activity in rats, p.o. 2 and 4 h after administration, respectively. Therefore, metabolic stability of the compounds was evaluated with use of rat microsomes, resulting in half‐life t1/2 136 and 108 min, respectively, indicating that either the metabolites are very active or the parent compounds exert ADME properties other than metabolism which influence the late onset of activity.
Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients
Authors: Guggino G , Ciccia F , Di Liberto D , Lo Pizzo M , Ruscitti P , Cipriani P , Ferrante A , Sireci G , Dieli F , Fourniè J J , Giacomelli R , Triolo G
Published: August 2016

Cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of γδ T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). γδ T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse transcription–polymerase chain reaction (RT–PCR). Peripheral blood mononuclear cells (PBMC), sorted γδ T cells and γδ cell lines were also stimulated in vitro with isopentenyl pyrophosphate (IPP), recombinant IL-9 or recombinant IL-23. Our results show an expansion of γδ T cells with a predominant effector memory phenotype in peripheral blood and synovium of untreated PsA patients, which reverses significantly after treatment with anti-TNF-α or anti-IL-12/IL-23R monoclonal antibodies (mAbs). Moreover, in PsA patients γδ T cells activation is driven prevalently by IL-9/IL-9R interaction, and not only by IL-23/IL-23R. Together these findings indicate γδ T cells and IL-9 as new players in the pathogenesis of PsA.
Cysteinyl Leukotrienes and Their Receptors: Emerging Therapeutic Targets in Central Nervous System Disorders
Authors: Ghosh Arijit , Chen Fang , Thakur Abhimanyu , Hong Hao
Published: August 2016

Cysteinyl leukotrienes are a group of the inflammatory lipid molecules well known as mediators of inflammatory signaling in the allergic diseases. Although they are traditionally known for their role in allergic asthma, allergic rhinitis, and others, recent advances in the field of biomedical research highlighted the role of these inflammatory mediators in a broader range of diseases such as in the inflammation associated with the central nervous system (CNS) disorders, vascular inflammation (atherosclerotic), and in cancer. Among the CNS diseases, they, along with their synthesis precursor enzyme 5‐lipoxygenase and their receptors, have been shown to be associated with brain injury, Multiple sclerosis, Alzheimer's disease, Parkinson's disease, brain ischemia, epilepsy, and others. However, a lot more remains elusive as the research in these areas is emerging and only a little has been discovered. Herein, through this review, we first provided a general up‐to‐date information on the synthesis pathway and the receptors for the molecules. Next, we summarized the current findings on their role in the brain disorders, with an insight given to the future perspectives.
Non‐HLA‐matched 3rd party vascular allograft in renal transplant may lead to sensitization against donor HLA
Authors: Watson Henry , Pande Rupaly , Farid Shahid , Ecuyer Clare , Baker Richard , Clarke Brendan , Ahmad Niaz
Published: August 2016

3rd party donor vessels are often used for vascular reconstruction in organ transplantation. While current practice ensures that 3rd party vessels are blood group matched, HLA matching to the non‐intended recipient is not performed. This practice potentially sensitizes the recipient and may reduce their future chance of renal transplant from a larger pool of donors. We examined our cohort of renal transplant recipients who received non‐HLA‐matched 3rd party vessels for the de‐novo development of donor‐specific HLA antibodies. Our institution's Human Tissue Authority (HTA) blood vessel registers were examined to identify stored donor vessels and their non‐intended recipients. Donor vessel HLA status was cross‐referenced with the recipient HLA status. Between 2004 and 2014, five patients were identified that received 3rd party non‐HLA‐matched vessels for vascular reconstruction during renal transplantation. Three patients (60%) subsequently developed donor‐specific HLA antibodies. These data provide evidence that use of non‐HLA‐matched stored 3rd party vascular grafts may lead to sensitization in the recipient. Where time permits, HLA matching should be performed to avoid this allogeneic response. Laboratories monitoring DSA should be aware of any patient receiving a non‐HLA‐matched 3rd party vascular graft, and recipients may benefit from increased post‐transplant immunological vigilance.
The prognostic values of caveolin‐1 immunoreactivity in peritubular capillaries in patients with kidney transplantation
Authors: Nakada Yasuyuki , Yamamoto Izumi , Horita Shigeru , Kobayashi Akimitsu , Mafune Aki , Katsumata Haruki , Yamakawa Takafumi , Katsuma Ai , Kawabe Mayuko , Tanno Yudo , Ohkido Ichiro , Tsuboi Nobuo , Yamamoto Hiroyasu , Okumi Masayoshi , Ishida Hideki , Yokoo Takashi , Tanabe Kazunari ,   Japan Academic Consortium of Kidney Transplantation (JACK)
Published: August 2016

The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody‐mediated rejection (CAAMR). C4d‐negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial‐associated transcripts (ENDATs). We previously showed that the ENDAT caveolin‐1 (CAV‐1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV‐1 immunoreactivity in PTCs in kidney transplant patients. Ninety‐eight kidney transplant recipients were included in this study. The prognostic value of CAV‐1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV‐1 and pathologische Anatomie Leiden endothelium (PAL‐E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV‐1/PAL‐E<50% and CAV‐1/PAL‐E≥50%. Kaplan‐Meier curves showed that CAV‐1/PAL‐E≥50% patients had a significantly worse prognosis than that of CAV‐1/PAL‐E<50% patients (log‐rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log‐rank; P=.345), whereas in a multivariate Cox regression analysis, CAV‐1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV‐1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival.
Prevalence, etiology, and clinical implications of reduced longitudinal systolic strain in renal transplant candidates
Authors: Rhea Isaac B. , Morris Kathleen , Sawada Stephen , Feigenbaum Harvey
Published: August 2016

Aims

Reduced global longitudinal systolic strain (GLS) is a common finding in end‐stage renal disease (ESRD) patients with normal ejection fraction (EF), and GLS is a stronger predictor of mortality than EF. We sought to determine what factors may be responsible for the decreased strain in this population.

Methods and Results

The study group was comprised of 139 renal transplant candidates with a normal EF who had echocardiography with assessment of GLS and basal longitudinal systolic strain (BLS). A GLS of less than −18 and a BLS less than −17 were defined as abnormal. Logistic regression was used to determine variables associated with abnormal GLS and BLS. Of the 139 patients, 49% had abnormal GLS and 70% had abnormal BLS. The univariate predictors of abnormal GLS (P<.05) were low‐normal EF, increased interventricular septal thickness (IVS), diabetes, and dihydropyridine calcium channel blocker use. The univariate predictors of abnormal BLS (P<.05) were elevated systolic blood pressure, elevated diastolic blood pressure, elevated heart rate, decreased EF, increased IVS, increased left ventricular posterior wall thickness (LVPW), increased left ventricular mass index, regular dialysis, and clonidine use. On multivariate analysis, low‐normal EF (P<.001), increased IVS (P=.024), and diabetes (P=.042) were independent predictors of abnormal GLS, while increased DBP (P=.018), increased LVPW (P=.001), and regular dialysis (P=.006) were independent predictors of abnormal BLS.

Conclusions

Clinical variables and co‐findings beyond EF are associated with abnormal strain measurements and may partially explain the large incidence of abnormal strain in renal transplant candidates.
Tissue Doppler imaging during exercise stress echocardiography demonstrates a mechanism for impaired exercise performance in children with hypertrophic cardiomyopathy
Authors: Ferguson Matthew Eric , Sachdeva Ritu , Gillespie Scott E. , Morrow Gemma , Border William
Published: August 2016

Background

Hypertrophic cardiomyopathy (HCM) is associated with decreased exercise tolerance in children, presumably due to diastolic dysfunction. Modern imaging techniques to assess myocardial function during active exercise have not been applied to this population. We hypothesized that impaired contractile reserve, as assessed by tissue Doppler imaging (TDI) and strain, contributes to reduced exercise capacity in affected individuals.

Methods

Children (<18 years) with HCM and healthy age‐ and sex‐matched controls were prospectively enrolled. Resting echocardiograms and staged upright cycle ergometry with simultaneous echocardiograms were performed. During exercise, left ventricular outflow tract (LVOT) gradients and color Doppler maps of apical four‐chamber and parasternal short‐axis views were obtained. Post processing of images was performed to obtain TDI velocities, and measurements of strain were attempted. Exercise parameters and staged TDI values were compared.

Results

The study population consisted of 58 subjects (22 with HCM and 36 controls). Patients with HCM had significantly higher peak LVOT gradients compared to controls at baseline and at each exercise stage. TDI revealed that diastolic function, as assessed by Eʹ velocities at septal and lateral mitral annuli, normalized with exercise in HCM patients. Further, systolic function (Sʹ velocity) of HCM patients at rest was normal but failed to augment normally at peak exercise.

Conclusions

Children with HCM have decreased TDI velocities at rest. With exercise, they may increase their Eʹ velocities but fail to augment Sʹ velocities, demonstrating decreased contractile reserve. In the patient with suspected HCM but equivocal findings, exercise TDI assessment may complement the diagnostic evaluation.
Mitral annular plane systolic excursion/left ventricular length (MAPSE/L) as a simple index for assessing left ventricular longitudinal function in children
Authors: Terada Tomomasa , Mori Kazuhiro , Inoue Miki , Yasunobu Hayabuchi
Published: August 2016

Background

Assessment of longitudinal left ventricular (LV) function is important for early detection of cardiac dysfunction. Although mitral annular plane systolic excursion (MAPSE) obtained by M‐mode echocardiography offers a simple method for assessing longitudinal LV function, normal values of MAPSE for children change according to body size.

Methods

To minimize the effects of body size, MAPSE was divided by LV long‐axis length (MAPSE/L). MAPSE/L was measured in 210 healthy children from birth to 15 years of age and classified into five subgroups. MAPSE/L was then compared with 10 parameters in 136 children (age, heart rate, mean blood pressure, ejection fraction of the LV (EF), peak atrial flow velocity/peak early diastolic flow velocity of mitral flow, tissue Doppler velocity during systole (s’) and early diastole (e’), E/e’ ratio, Tei index, and global longitudinal strain (GLS) of the LV by the speckle tracking method).

Results

MAPSE/L was significantly lower in the neonate group than in the remaining four groups. MAPSE/L then increased with age to peak at 1–5 years and gradually decreased thereafter. In all cases beyond the neonatal period, MAPSE/L was more than 0.17. Among various parameters, GLS, age, EF, Tei index and s’ were significantly associated with MAPSE/L in that order. In univariate analysis, GLS was most significantly associated with MAPSE/L (r=.56).

Conclusions

We have established normal reference values for MPSE/L in healthy children. MAPSE/L is expected to offer a simple parameter to evaluate LV longitudinal systolic function during daily routine echocardiography in children.
Echocardiography vs magnetic resonance imaging in assessing ventricular function and systemic atrioventricular valve status in adults with congenitally corrected transposition of the great arteries
Authors: Kowalik Ewa , Mazurkiewicz Łukasz , Kowalski Mirosław , Klisiewicz Anna , Marczak Magdalena , Hoffman Piotr
Published: August 2016

Background

The survival in adults with congenitally corrected transposition of the great arteries (ccTGA) might be reduced due to dysfunction of the systemic right ventricle (sRV). The quantitative echocardiographic assessment of sRV function and tricuspid (systemic atrioventricular valve) regurgitation (TR) is still a diagnostic challenge. Thus, the aim of this study was to compare echocardiographic indices of sRV function and the degree of TR with corresponding MRI (magnetic resonance imaging)‐derived parameters in adults with ccTGA.

Methods

A prospective cross‐sectional study of adults with ccTGA referred to a tertiary congenital heart disease center was conducted. All patients underwent transthoracic echocardiography and MRI examinations. Thirty‐three adults (19F/14M, mean age 34.1 years) were included.

Results

We found significantly lower fractional area change (FAC) and global longitudinal strain (GLS) values in patients with MRI‐derived RV ejection fraction (EF) <45%. A cutoff GLS<−16.3% identified sRV EF ≥45% with a sensitivity of 77.3% and specificity of 72.7%. A very strong correlation between MRI‐ and echocardiography‐derived TR volume was observed (r=.84; P<.0001).

Conclusions

GLS is the variable with the best sensitivity but less specificity to distinguish between systemic RV EF ≥45% and below 45%, and it seems to be the preferred echocardiographic index of systemic RV function in adults with ccTGA. The quantitative assessment of TR by MRI and echocardiography showed a very strong agreement in patients with ccTGA.
Occupational musculoskeletal pain in cardiac sonographers compared to peer employees: a multisite cross‐sectional study
Authors: Orme Nicholas M. , Geske Jeffrey B. , Pislaru Sorin V. , Askew John Wells , Lennon Ryan J. , Lewis Bradley R. , Rihal Charanjit S. , Pellikka Patricia A. , Singh Mandeep
Published: August 2016

Objectives

The purpose of this study was to compare the prevalence and impact of work‐related musculoskeletal pain in cardiac sonographers to a large control group of peer employees with similar demographics.

Background

Cardiac sonographers are known to have high levels of occupational musculoskeletal pain. Comparative studies with other employees within cardiology/radiology departments have never been performed.

Methods

An electronic survey was administered to Mayo Clinic employees at six major patient care facilities in four different states.

Results

There were 2682 employees within the departments of cardiology and radiology who were contacted, and 1532 (57%) completed the survey. After excluding those who wore protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers reported work‐related musculoskeletal pain more frequently than the control group (88% vs 40%; P<.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment, and history of preexisting musculoskeletal pain (OR 11.6; [95% CI 5.32, 25.5]; P<.001). Cardiac sonographers sought medical care for their work‐related pain more often (55% vs 21%; P<.001) and missed more work due to pain (35% vs 12%, P<.001). In a secondary analysis, cardiac sonographers also experienced more work‐related musculoskeletal pain than nurses, technicians, and physicians working in the interventional laboratory who regularly wear a protective lead apron (P<.001).

Conclusions

In this multisite cross‐sectional study, cardiac sonographers experienced significantly more work‐related pain and missed more work due to pain than peer employees within cardiology/radiology departments.
Economists, Research Performance and National Inbreeding: North Versus South
Authors: Katranidis Stelios , Panagiotidis Theodore , Zontanos Costas
Published: August 2016

We investigate the research performance of 404 economists working in 17 Economics Departments and 4 countries. Two countries from the North of Europe (Belgium and Denmark) are compared with two countries from the South (Greece and Portugal) in terms of research productivity. Their performance is ranked using bibliometric indices. We examine the factors that drive economist's research performance using OLS and quantile regression analysis. The most productive economists have a US PhD and work in the North. Inbreeding at the national level is associated with higher productivity in the North and lower in the South.
Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte‐mediated neuroprotection after oxygen–glucose deprivation and reoxygenation
Authors: Zhang Han , Xiao Jun , Hu Zheng , Xie Minjie , Wang Wei , He Dan
Published: August 2016

Astrocytes play important roles in homeostatic regulation in the central nervous system and are reported to influence the outcome of ischemic injury. Regulating Ca2+ signaling of astrocytes is a promising strategy for stroke therapy. Herein, we report for the first time that transient receptor potential vanilloid 2 (TRPV2), a Ca2+‐permeable channel that is important in osmotic balance regulation, expresses in rat cortical astrocytes by immunofluorescence. Moreover, oxygen‐glucose deprivation and reoxygenation (OGD/R) treatment enhanced the expression. The TRPV2 is functional because Ca2+ imaging showed that activating the TRPV2 channel in cultured astrocytes increased intracellular Ca2+ level and the increment of intracellular Ca2+ level expanded when astrocytes were treated with OGD/R. Staining with 5‐ethynyl‐2′‐deoxyuridine (EdU) revealed that while blocking the TRPV2, it promoted the proliferation of astrocytes. Additionally, blocking the TRPV2 in astrocytes increased the synthesis of nerve growth factor (NGF) mRNA and the secretion of NGF by real‐time PCR and enzyme‐linked immunosorbent assay respectively. We further found that the increased secretion of NGF could be reversed by c‐JunN‐terminalkinase (JNK) inhibitor and blocking the TRPV2 caused the phosphorylation of JNK. These indicated that blocking the TRPV2 induced NGF secretion via the mitogen‐activated protein kinase (MAPK)‐JNK signaling pathway. As the promoted proliferation of astrocytes and secretion of NGF were reported to have neuroprotective effects in the early stage of stroke, we concluded that targeting the TRPV2 channel in astrocytes might be a potential new therapeutic strategy in ischemic stroke.
Temporally stable adaptation is robust, incomplete and specific
Authors: van der Kooij Katinka , Overvliet Krista E. , Smeets Jeroen B. J.
Published: August 2016

Sensorimotor adaptation, the process that reduces movement errors by learning from sensory feedback, is often studied within a session of about half an hour. Within such a single session, adaptation generally reaches plateau before errors are completely removed. However, adaptation may complete on longer timescales: the slow components of error‐based adaptation are associated with good retention. In this study, we tested how adaptation evolves over time by asking participants to perform six adaptation sessions on different days. In these sessions, participants performed a three‐dimensional reaching task while visual feedback about endpoint errors was rotated around the cyclopean eye. In addition, context specificity of the adaptation was addressed by measuring inter‐limb transfer and transfer to visual and proprioceptive perceptual tasks. We show that from the second session on, the adaptation was retained almost completely across sessions. However, after six learning sessions, adaptation still reached plateau before errors were completely removed. The adaptation was specific: the adaptation did neither transfer to the other hand, nor to the visual, and only marginally to the proprioceptive perceptual estimates. We conclude that motor adaptation is robust, specific and incomplete.
Territory Availability at Different Spatial Scales does not Affect Fighting Investment in Males of the Lycaenid Butterfly Strymon mulucha
Authors: Ferreira Cibele P. S. , Cerqueira Luana P. , Uezu Alexandre , Oliveira Eddy J. F. , Peixoto Paulo E. C.
Published: August 2016

In territorial species, rivals investment in fights over territories may increase when the availability of suitable areas for defense is low. This should occur because low territory availability may increase the costs to maintain and acquire territories. Although such process occurs in small spatial scales (local scale), territory availability in larger scales (regional scale) may also affect fighting investment, as losers should incur additional dispersing costs to find new territories. In this study, we used males of the hilltopping butterfly Strymon mulucha to evaluate the hypothesis that males should invest more in territorial fights when the costs to find new territories are higher (both at local and at regional scale). We timed male–male contests for territories located in 12 hilltops and measured male density per territory in each hilltop (local scale). We also quantified the distance between hilltops containing suitable areas for territories (regional scale). Male–male contests lasted 21 s on average, and copulations did not occur during the observations. The duration of contests was unrelated to the male density per territory or to the distance among hilltops, indicating that the investment in fights was unaffected by the availability of territorial sites, independent of the spatial scale. As male–male contests in S. mulucha are longer than the mean contest duration in other butterfly species and mating is extremely rare, we suggest that the value of each territory may be high enough to favor males that always invest as much as possible in contests.