bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergic sensitization to pegylated interferon‐α results in drug eruptions
Authors: Meller S. , Gerber P. A. , Kislat A. , Hevezi P. , Göbel T. , Wiesner U. , Kellermann S. , Bünemann E. , Zlotnik A. , Häussinger D. , Erhardt A. , Homey B.
Published: April 2015

Background

The introduction of pegylated interferon (PEG‐IFN)‐α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)‐α, a high frequency of adverse cutaneous reactions has been reported with pegylatedIFN‐α. Here, we aimed to investigate the immunological mechanisms underlying pegylatedIFN‐α‐induced drug eruptions.

Methods

Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylatedIFN‐α2a, pegylatedIFN‐α2b, or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylatedIFN‐α‐associated exanthemas, as well as from localized inflammatory skin reactions at pegylatedIFN‐α injection sites, were analyzed for the expression of relevant chemokines by quantitative real‐timePCRand immunohistochemistry.

Results

A subset of patients suffering from pegylatedIFN‐α‐associated exanthemas displayed positive intradermal tests toPEG‐IFNs but not to conventionalIFN(11/22). In selected patients, this observation correlated with the presence of pegylatedIFN‐specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected anIFN‐α‐signature, whereas lesional skin of exanthemas showed induction ofTH2‐associated chemokines.

Conclusions

Our results indicate that specific sensitizations are one cause of exanthemas under therapy withPEG‐IFNs. Clinical proof‐of‐concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enablingIFN‐α therapy continuation without drug‐associated skin eruptions.
Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization
Authors: Alvarez‐Cuesta E. , Madrigal‐Burgaleta R. , Angel‐Pereira D. , Ureña‐Tavera A. , Zamora‐Verduga M. , Lopez‐Gonzalez P. , Berges‐Gimeno M. P.
Published: April 2015

Background

Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of includingDPTas a paramount gold standard diagnostic tool (prior to desensitization).

Methods

Prospective, observational, longitudinal study with patients who, during a 3‐year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, andDPT. Oxaliplatin‐specific IgE was determined in oxaliplatin‐reactive patients (who underwentDPTregardless of oxaliplatin‐specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables.

Results

A total of 186 patients were assessed. A total of 104 (56%) patients underwentDPT. Sixty‐four percent of allDPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin‐specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5.

Conclusions

These are the first reported data based on more than 100DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation ofDPTin diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30–56% of patients, depending on culprit‐drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin‐specific IgE and oxaliplatin‐STin the largest series of oxaliplatin‐reactive patients reported to date (74 oxaliplatin‐reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans.
Management of immune thrombocytopenia in adults: a population‐based analysis of the French hospital discharge database from 2009 to 2012
Authors: Michel Marc , Suzan Florence , Adoue Daniel , Bordessoule Dominique , Marolleau Jean‐Pierre , Viallard Jean‐François , Godeau Bertrand
Published: April 2015

The present study describes the current clinical practice and hospital management of adults with immune thrombocytopenia (ITP) between 2009 and 2012 in France, based on the national discharge hospital database. Adult ITP patients were managed almost exclusively in public hospitals. A relatively stable number of patients, around 3200 per year, were hospitalized for ITP annually over the 4‐year period, about two‐thirds of whom were newly‐diagnosed ITP. Re‐hospitalizations tended to decrease over the study period. Intravenous immunoglobulin administration, concerning half of ITP hospitalized patients, and rituximab administration were stable over time, whereas a slight decrease of splenectomies was observed.
Aspirin‐induced histone acetylation in endothelial cells enhances synthesis of the secreted isoform of netrin‐1 thus inhibiting monocyte vascular infiltration
Authors: Passacquale Gabriella , Phinikaridou Alkystis , Warboys Christina , Cooper Margaret , Lavin Begona , Alfieri Alessio , Andia Marcelo E , Botnar Rene M , Ferro Albert
Published: April 2015

Background and Purpose

There are conflicting data regarding whether netrin‐1 retards or accelerates atherosclerosis progression, as it can lead either to monocyte repulsion from or retention within plaques depending on its cellular source. We investigated the effect of aspirin, which is widely used in cardiovascular prophylaxis, on the synthesis of different isoforms of netrin‐1 by endothelial cells under pro‐inflammatory conditions, and defined the net effect of aspirin‐dependent systemic modulation of netrin‐1 on atherosclerosis progression.

Experimental Approach

Netrin‐1 synthesis was studied in vitro using human endothelial cells stimulated with TNF‐α, with or without aspirin treatment. In vivo experiments were conducted in ApoE−/− mice fed with a high‐fat diet (HFD), receiving either aspirin or clopidogrel.

Key Results

TNF‐α‐induced NF‐κB activation up‐regulated the nuclear isoform of netrin‐1, while simultaneously reducing secreted netrin‐1. Down‐regulation of the secreted isoform compromised the chemorepellent action of the endothelium against monocyte chemotaxis. Aspirin counteracted TNF‐α‐mediated effects on netrin‐1 synthesis by endothelial cells through COX‐dependent inhibition of NF‐κB and concomitant histone hyperacetylation. Administration of aspirin to ApoE−/− mice on HFD increased blood and arterial wall levels of netrin‐1 independently of its effects on platelets, accompanied by reduced plaque size and content of monocytes/macrophages, compared with untreated or clopidogrel‐treated mice. In vivo blockade of netrin‐1 enhanced monocyte plaque infiltration in aspirin‐treated ApoE−/− mice.

Conclusions and Implications

Aspirin counteracts down‐regulation of secreted netrin‐1 induced by pro‐inflammatory stimuli in endothelial cells. The aspirin‐dependent increase of netrin‐1 in ApoE−/− mice exerts anti‐atherogenic effects by preventing arterial accumulation of monocytes.
A derivative of epigallocatechin‐3‐gallate induces apoptosis via SHP‐1‐mediated suppression of BCR‐ABL and STAT3 signalling in chronic myelogenous leukaemia
Authors: Jung Ji Hoon , Yun Miyong , Choo Eun‐Jeong , Kim Sun‐Hee , Jeong Myoung‐Seok , Jung Deok‐Beom , Lee Hyemin , Kim Eun‐Ok , Kato Nobuo , Kim Bonglee , Srivastava Sanjay K , Kaihatsu Kunihiro , Kim Sung‐Hoon
Published: April 2015

Background and Purpose

Epigallocatechin‐3‐gallate (EGCG) is a component of green tea known to have chemo‐preventative effects on several cancers. However, EGCG has limited clinical application, which necessitates the development of a more effective EGCG prodrug as an anticancer agent.

Experimental Approach

Derivatives of EGCG were evaluated for their stability and anti‐tumour activity in human chronic myeloid leukaemia (CML) K562 and KBM5 cells.

Key Results

EGCG‐mono‐palmitate (EGCG‐MP) showed most prolonged stability compared with other EGCG derivatives. EGCG‐MP exerted greater cytotoxicity and apoptosis in K562 and KBM5 cells than the other EGCG derivatives. EGCG‐MP induced Src‐homology 2 domain‐containing tyrosine phosphatase 1 (SHP‐1) leading decreased oncogenic protein BCR‐ABL and STAT3 phosphorylation in CML cells, compared with treatment with EGCG. Furthermore, EGCG‐MP reduced phosphorylation of STAT3 and survival genes in K562 cells, compared with EGCG. Conversely, depletion of SHP‐1 or application of the tyrosine phosphatase inhibitor pervanadate blocked the ability of EGCG‐MP to suppress phosphorylation of BCR‐ABL and STAT3, and the expression of survival genes downstream of STAT3. In addition, EGCG‐MP treatment more effectively suppressed tumour growth in BALB/c athymic nude mice compared with untreated controls or EGCG treatment. Immunohistochemistry revealed increased caspase 3 and SHP‐1 activity and decreased phosphorylation of BCR‐ABL in the EGCG‐MP‐treated group relative to that in the EGCG‐treated group.

Conclusions and Implications

EGCG‐MP induced SHP‐1‐mediated inhibition of BCR‐ABL and STAT3 signalling in vitro and in vivo more effectively than EGCG. This derivative may be a potent chemotherapeutic agent for CML treatment.
Spinal antinociceptive effects of the novel NOP receptor agonist PWT2‐nociceptin/orphanin FQ in mice and monkeys
Authors: Rizzi A , Sukhtankar D D , Ding H , Hayashida K , Ruzza C , Guerrini R , Calò G , Ko M C
Published: April 2015

Background and purpose

Using an innovative chemical approach, peptide welding technology (PWT), a tetrabranched derivative of nociceptin/orphanin FQ (N/OFQ) has been generated and pharmacologically characterized. Both in vitro and in vivo PWT2‐N/OFQ displayed the same pharmacological profile to the natural ligand. It was more potent and produced longer‐lasting effects. The aim of the present study was to investigate the spinal effects of PWT2‐N/OFQ in nociceptive and neuropathic pain models in mice and non‐human primates.

Experimental Approach

Tail withdrawal assay in mice and monkeys was used as a nociceptive pain model and mechanical threshold in mice subjected to chronic constriction injury was used as a neuropathic pain model. The antinociceptive effects of spinally administered N/OFQ and PWT2‐N/OFQ were assessed in these models.

Key Results

PWT2‐N/OFQ mimicked the spinal antinociceptive effects of N/OFQ both in nociceptive and neuropathic pain models in mice as well as in non‐human primates displaying 40‐fold higher potency and a markedly prolonged duration of action. The effects of N/OFQ and PWT2‐N/OFQ were sensitive to the N/OFQ receptor (NOP) antagonist SB‐612111, but not to opioid receptor antagonists.

Conclusions and Implications

The present study has demonstrated that PWT2‐N/OFQ mimicked the antinociceptive effects of the natural peptide in rodents and non‐human primates acting as a potent and longer‐lasting NOP‐selective agonist. More generally, PWT derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects.
PKPD modelling to predict altered disposition of 1α,25‐dihydroxyvitamin D3 in mice due to dose‐dependent regulation of CYP27B1 on synthesis and CYP24A1 on degradation
Authors: Quach Holly P , Yang Qi J , Chow Edwin C , Mager Donald E , Hoi Stacie Y , Pang K Sandy
Published: April 2015

Background and Purpose

Concentrations of 1α,25‐dihydroxyvitamin D3 [1,25(OH)2D3], the active ligand of the vitamin D receptor, are tightly regulated by CYP27B1 for synthesis and CYP24A1 for degradation. However, the dose‐dependent pharmacokinetic (PK)‐pharmacodynamic (PD) relationship between these enzymes and 1,25(OH)2D3 concentrations has not been characterized.

Experimental Approach

The pharmacokinetics of 1,25(OH)2D3 were evaluated after administration of single (2, 60 and 120 pmol) and repeated (2 and 120 pmol q2d ×3) i.v. doses to male C57BL/6 mice. mRNA expression of CYP27B1 and CYP24A1 was examined by quantitative PCR and 1,25(OH)2D3 concentrations were determined by enzyme immunoassay.

Key Results

CYP27B1 and CYP24A1 changes were absent for the 2 pmol dose and biexponential decay profiles showed progressively shorter terminal half‐lives with increasing doses. Fitting with a two‐compartment model revealed decreasing net synthesis rates and increasing total clearances with dose, consistent with a dose‐dependent down‐regulation of renal CYP27B1 and the induction of renal/intestinal CYP24A1 mRNA expression. Upon incorporation of PD parameters for inhibition of CYP27B1 and induction of CYP24A1 to the simple two‐compartment model, fitting was significantly improved. Moreover, fitted estimates for the 2 pmol dose, together with the PD parameters as modifiers, were able to predict profiles reasonably well for the higher (60 and 120 pmol) doses. Lastly, an indirect response model, which considered the synthesis and degradation of enzymes, adequately described the PK and PD profiles.

Conclusions and Implications

The unique PK of exogenously administered 1,25(OH)2D3 led to changes in PD of CYP27B1 and CYP24A1, which hastened the clearance of 1,25(OH)2D3.
Inflammation in acute CNS injury: a focus on the role of substance P
Authors: Corrigan F , Vink R , Turner R J
Published: April 2015

Recently, a number of reports have shown that neurogenic inflammation may play a role in the secondary injury response following acute injury to the CNS, including traumatic brain injury (TBI) and stroke. In particular substance P (SP) release appears to be critically involved. Specifically, the expression of the neuropeptide SP is increased in acute CNS injury, with the magnitude of SP release being related to both the frequency and magnitude of the insult. SP release is associated with an increase in blood–brain barrier permeability and the development of vasogenic oedema as well as neuronal injury and worse functional outcome. Moreover, inhibiting the actions of SP through use of a NK1 receptor antagonist is highly beneficial in both focal and diffuse models of TBI, as well as in ischaemic stroke, with a therapeutic window of up to 12 h. We propose that NK1 receptor antagonists represent a novel therapeutic option for treatment of neurogenic inflammation following acute CNS injury.

Linked Articles

This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
Recovery of Amphibian and Reptile Assemblages During Old‐Field Succession of Tropical Rain Forests
Authors: Hernández‐Ordóñez Omar , Urbina‐Cardona Nicolas , Martínez‐Ramos Miguel
Published: April 2015

Conversion of tropical forests to agriculture affects vertebrate assemblages, but we do not know how fast or to what extent these assemblages recover after field abandonment. We addressed this question by examining amphibians and reptiles in secondary forests in southeastern Mexico. We used chronosequence data (12 secondary forests fallow for 1–23 yr and 3 old‐growth forest sites) to analyze successional trajectories and estimate recovery times of assemblage attributes for amphibians and reptiles. We conducted 6 surveys at each site over 14 mo (1200 person‐hours) and recorded 1552 individuals, including 25 species of amphibians and 36 of reptiles, representing 96 and 74 percent of the expected regional number of species, respectively. Abundance, species richness, and species diversity of amphibians increased rapidly with successional age, approaching old‐growth forest values in < 30 yr. Species richness and species diversity of reptiles reached old‐growth forest values in < 20 yr. By contrast, the abundance of reptiles and the assemblage composition of amphibians and reptiles recovered more slowly. Along the chronosequence, we observed more species replacement in reptile assemblages than in amphibian assemblages. Several species in the old‐growth forest were absent from secondary forests. Dispersal limitation and harsh conditions prevailing in open sites and early successional environments appear to preclude colonization by old‐growth forest species. Furthermore, short fallow periods and isolation of forest remnants lead to the formation of new assemblages dominated by species favored by human disturbances.
Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact
Authors: Komura Takuya , Sakai Yoshio , Harada Kenichi , Kawaguchi Kazunori , Takabatake Hisashi , Kitagawa Hirohisa , Wada Takashi , Honda Masao , Ohta Tetsuo , Nakanuma Yasuni , Kaneko Shuichi
Published: April 2015

Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death‐1 (PD‐1). Concentrations of interleukin (IL)‐6, IL‐7, IL‐15, monocyte chemotactic protein‐1, and interferon‐γ‐inducible protein‐1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD‐1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD‐1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis.
ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma
Authors: Zhang Guiming , Gu Chengyuan , Zhu Yao , Luo Lei , Dong Dahai , Wan Fangning , Zhang Hailiang , Shi Guohai , Sun Lijiang , Ye Dingwei
Published: April 2015

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.
The potential role of benefit and burden finding in school engagement of young leukaemia survivors: an exploratory study
Authors: Tougas A.‐M. , Jutras S. , Bigras M. , Tourigny M.
Published: April 2015

Background

Childhood cancer may radically change the daily lives of young survivors, particularly in school. Depending on the sense they derive from the experience of illness, survivors may go through profound transformations in the way they approach life.

Methods

This exploratory study reports on school engagement of cancer survivors by examining their perceptions of benefits and burdens in relation to their illness. Forty‐nine young Quebecers, previously diagnosed and treated for leukaemia, completed a questionnaire measuring their school engagement and participated in an interview focusing on the impact of cancer on their lives. Perceptions with regard to the presence and types of benefits and burdens were described and examined in light of participants' characteristics. An analysis of variance explored whether the presence/absence of benefits and burdens were associated with participants' scores regarding school engagement.

Results

Most participants mentioned benefits from having had cancer, and in particular benefits at an interpersonal level. Half of the participants mentioned burdens, mainly of a physical and psychological nature. Significant correlations indicated that (i) the older the survivors were, the more likely they were to report benefits in terms of qualities and strengths of character; (ii) the more time had elapsed since their diagnosis, the more survivors were likely to report psychological types of burdens; and (iii) children from single‐parent families reported more frequently having appreciated social or recreational activities compared with children from two‐parent families. One main effect indicated that school engagement was greater for survivors who perceived the presence of benefits. An interaction effect revealed that the perception of both benefits and burdens predicts the highest scores of school engagement.

Conclusions

While the results reveal the promising potential that an optimistic yet realistic disposition has in regard to school engagement, more research is necessary to further our understanding of such a disposition.
Diagnostic pitfall in antenatal manifestations ofCPT IIdeficiency
Authors: Boemer F. , Deberg M. , Schoos R. , Caberg J.‐H. , Gaillez S. , Dugauquier C. , Delbecque K. , François A. , Maton P. , Demonceau N. , Senterre G. , Ferdinandusse S. , Debray F.‐G.
Published: April 2015

Carnitine palmitoyltransferaseII(CPT2) deficiency is a rare inborn error of mitochondrial fatty acid metabolism associated with various phenotypes. Whereas most patients present with postnatal signs of energetic failure affecting muscle and liver, a small subset of patients presents antenatal malformations including brain dysgenesis and neuronal migration defects. Here, we report recurrence of severe cerebral dysgenesis with Dandy–Walker malformation in three successive pregnancies and review previously reported antenatal cases. Interestingly, we also report that acylcarnitines profile, tested retrospectively on the amniotic fluid of last pregnancy, was not sensitive enough to allow reliable prenatal diagnosis ofCPT2deficiency. Finally, because fetuses affected by severe cerebral malformations are frequently aborted,CPT2deficiency may be underestimated and fatty acid oxidation disorders should be considered when faced with a fetus with Dandy–Walker anomaly or another brain dysgenesis.
The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: a systematic review and retrospective multicentre analysis
Authors: Swartz J.E. , Aarts M.C.J. , Swart K.M.A. , Disa J.J. , Gerressen M. , Kuo Y.‐R. , Wax M.K. , Grolman W. , Braunius W.W.
Published: April 2015

Background

Free radial forearm flap (FRFF) reconstruction is a valuable technique in head and neck surgery, which allows closure of large defects while striving to maintain functionality. Anticoagulative drugs are often administered to improve flap survival, although evidence regarding effectiveness is lacking.

Objective of review

To investigate the effectiveness of postoperative anticoagulants to improve survival of the FRFF in head and neck reconstruction.

Type of review

Systematic review and multicentre, individual patient data meta‐analysis.

Search strategy

MEDLINE, EMBASE, Web of Science and CINAHL were searched for synonyms of ‘anticoagulants’ and ‘free flap reconstruction’.

Evaluation method

Studies were critically appraised for directness of evidence and risk of bias. Authors of the highest quality publications were invited to submit their original data for meta‐analysis.

Results

Five studies were of adequate quality, and data from four studies (80%) were available for meta‐analysis, describing 759 FRFF procedures. Anticoagulants used were as follows: aspirin (12%), low molecular weight dextran (18.3%), unfractioned heparin (28.1%), low molecular weight heparin (49%) and prostaglandin‐E1 (2.1%). Thirty‐one per cent did not receive anticoagulants. Flap failure occurred in 40 of 759 patients (5.3%) On univariate analysis, use of unfractioned heparin was associated with a higher rate of flap failure. However, these regimens were often administered to patients who had revision surgery of the anastomosis. In multivariate logistic regression analysis, anticoagulant use was not associated with improved flap survival or flap‐related complications.

Conclusions

The studied anticoagulative drugs did not improve FRFF survival or lower the rate of flap‐related complications. In addition, some anticoagulants may cause systemic complications.
Utility of biological sensor tags in animal conservation
Authors: Wilson A.D.M. , Wikelski M. , Wilson R.P. , Cooke S.J.
Published: April 2015

Electronic tags (both biotelemetry and biologging platforms) have informed conservation and resource management policy and practice by providing vital information on the spatial ecology of animals and their environments. However, the extent of the contribution of biological sensors (within electronic tags) that measure an animal's state (e.g., heart rate, body temperature, and details of locomotion and energetics) is less clear. A literature review revealed that, despite a growing number of commercially available state sensor tags and enormous application potential for such devices in animal biology, there are relatively few examples of their application to conservation. Existing applications fell under 4 main themes: quantifying disturbance (e.g., ecotourism, vehicular and aircraft traffic), examining the effects of environmental change (e.g., climate change), understanding the consequences of habitat use and selection, and estimating energy expenditure. We also identified several other ways in which sensor tags could benefit conservation, such as determining the potential efficacy of management interventions. With increasing sensor diversity of commercially available platforms, less invasive attachment techniques, smaller device sizes, and more researchers embracing such technology, we suggest that biological sensor tags be considered a part of the necessary toolbox for conservation. This approach can measure (in real time) the state of free‐ranging animals and thus provide managers with objective, timely, relevant, and accurate data to inform policy and decision making.
Kidney transplant complications from undiagnosed benign prostatic hypertrophy
Authors: Lubetzky Michelle , Ajaimy Maria , Kamal Layla , de Boccardo Graciela , Akalin Enver , Kayler Liise
Published: April 2015

Background

It is estimated that approximately 50% of males over 50 have benign prostatic hypertrophy (BPH). BPH is underappreciated in anuric patients with end stage renal disease, and failure of diagnosis in this population can lead to complications after kidney transplantation.

Methods

A single‐center retrospective review of male patients over 50 yr of age transplanted from January 1, 2010, until September 30, 2013, was performed. Outcomes assessed were as follows: graft survival, urinary retention, discharge with Foley catheter, and urinary tract infection (UTI).

Results

Of 147 patients, 17.0% were diagnosed with BPH before transplant, 19.0% received a BPH diagnosis after transplant, and 64% did not have BPH. Compared to those without BPH, a post‐transplant BPH diagnosis was associated with urinary retention during the transplant admission (0% vs. 46.4%, p < 0.01), discharge with Foley catheter (0% vs. 21.4%, p < 0.01), readmission related to urinary retention (0% vs. 46.4%, p < 0.01), and UTI (18.0% vs. 64.3%, p < 0.01). Patients with prior diagnosis of BPH and on therapy had similar outcomes to those without BPH.

Conclusions

Following kidney transplant, urinary tract complications are more common in patients with BPH; however, being on medical therapy prior to transplantation diminishes the incidence of these complications significantly.
Measurement of body composition should become routine in nutritional assessment of children with cerebral palsy
Authors: Sullivan Peter
Published: April 2015

This commentary is on the original article by Finbråten et al. on pages858–864of this issue.
Comparing and sharing information across health care settings: a difficult but potentially invaluable task
Authors: Day Steven
Published: April 2015

This commentary is on the original article by Horridge et al. on pages 844–851 of this issue.
In prostate cancer, low adiponectin levels are not associated with insulin resistance
Authors: Michalakis Konstantinos , Venihaki Maria , Mantzoros Christos , Vazaiou Andriani , Ilias Ioannis , Gryparis Alexandros , Margioris Andrew N.
Published: April 2015

Purpose

Adiponectin, an adipose tissue‐derived hormone with insulin‐sensitizing effect, has been inversely associated with several hormonally dependent malignancies. Prostate cancer is associated with low levels of adiponectin, which have been proposed as an independent risk factor for this malignancy. Aim of this study was to examine whether hypoadiponectinaemia in prostate is associated with insulin resistance.

Experimental Design

Plasma samples and covariate data in the context of a case–control study of 300 Greek men were evaluated including 75 patients with prostate cancer, 75 patients with benign prostatic hyperplasia (BPH) and 150 age‐matched healthy controls.

Results

Patients with prostate cancer had significantly lower plasma adiponectin levels compared with the other two groups, that is BPH patients and healthy controls (7·4 ± 5 ng/mL vs. 11·5 ± 6·4 ng/mL and 12·8 ± 8 ng/mL, respectively). On the other hand, no statistically significant differences were found between patients with prostate cancer and the other two groups for both HOMA‐IR and QUICKI (P‐value = 0·551). As expected, in all three groups, the levels of adiponectin correlated negatively with HOMA‐IR (rho = −0·214, P‐value = 0·006), QUICKI (rho = 0·214, P‐value = 0·006) and insulin levels (rho = 0·942, P‐value<0·001).

Conclusion

In spite of what would have been expected from the relevant literature, our data suggest that the hypoadiponectinaemia in prostatic cancer does not appear to be associated with insulin resistance.
Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol
Authors: Guedes A. , Knych H. , Hood D.
Published: April 2015

Reasons for performing study

Laminitis is a painful disease for which adequate pain management remains a challenging and largely unmet medical need.

Objectives

To investigate plasma concentrations, analgesic and physiological effects of 2 doses of tramadol in horses with chronic laminitis.

Study design

Nonrandomised trial.

Methods

Four horses with naturally occurring chronic laminitis received 5 mg/kg bwt and then 10 mg/kg bwt tramadol orally every 12 h for one week with a one‐week washout between. Noninvasive arterial blood pressure, heart and respiratory rates, intestinal sounds and forelimb off‐loading frequency were evaluated before and during treatments. Plasma tramadol and metabolite (M1 and M2) concentrations were measured on predetermined days and times after the morning dosing.

Results

Forelimb off‐loading frequency decreased significantly with 10 mg/kg bwt (40%, P = 0.02) but not with 5 mg/kg bwt (9%, P = 0.4). Physiological variables did not change significantly with either treatment. For 5 and 10 mg/kg bwt treatments, respectively, individual maximum plasma concentrations (μg/l) ranged from 329 to 728 and 628 to 1330 (tramadol), 12–24 and 32–80 (M1), and 90–157 and 239–362 (M2). Respective median area under the concentration vs. time curves (h μg/l) were 727 and 1426, 33 and 88, 303 and 1003.

Conclusions

Twice daily oral tramadol at 10 mg/kg bwt may produce analgesic plasma levels in horses with chronic laminitis.
Ex vivo human skin and SZ95 sebocytes exhibit a homoeostatic interaction in a novel coculture contact model
Authors: Nikolakis Georgios , Seltmann Holger , Hossini Amir M. , Makrantonaki Evgenia , Knolle Jürgen , Zouboulis Christos C.
Published: April 2015

The sebaceous gland displays key functions of the human skin, such as hormone synthesis in situ, antimicrobial activity and participation to inflammatory responses. Consequently, there is an emerging need of advanced in vitro models to study complex interactions between the sebaceous gland and the other skin compartments. Despite the evolution of both full‐skin organ culture and reconstructed three‐dimensional skin models, no satisfactory solutions have been provided for the integration of sebaceous glands and/or sebaceous gland cells in those models, probably due to their problematic maintenance both in vitro and ex vivo. We have developed a coculture model of explant skin in direct contact with immortalized SZ95 sebocytes, which resulted in overall improved structural integrity of the epidermis, higher percentage of proliferating basal epidermal cells and reduced apoptosis of differentiating keratinocytes after 6 days, as detected by Ki67 and TUNEL staining, respectively. Furthermore SZ95 sebocytes exhibited morphological and biochemical signs of normal differentiation and lipid accumulation, while interleukin‐6 expression in the supernatant of the cocultures was decreased in comparison with the control. The data provide evidence of a beneficial interaction between sebocytes and skin explants and provide the rationale for their integration in future three‐dimensional skin models.
Molecular mechanism of ER stress‐induced gene expression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) in macrophages
Authors: Huang Yan , Wang Yarui , Li Xiaofeng , Chen Zhaolin , Li Xiaohui , Wang Huan , Ni Mingming , Li Jun
Published: April 2015

Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, whose members are capable of inducing apoptosis and inflammation. Endoplasmic reticulum stress (ERS) plays a key role in immune surveillance in macrophages. TRAIL mRNA and protein expression have previously been detected in macrophages; however, whether ERS has any effects on TRAIL expression in macrophages has not yet been determined. Here, we demonstrate that thapsigargin (TG) and tunicamycin (TM), two ERS inducers activated macrophages were able to increase TRAIL mRNA and protein expression in RAW264.7 macrophages, the culture supernatant of THP‐1 cells, and mouse peritoneal macrophages, indicating that ERS as a potent inducer of TRAIL transcription and expression in macrophages. This effect was blocked by the specific JNK inhibitor SP600125 and transcription factor AP‐1 inhibitor SR 1130. Interestingly, at the molecular level, regulation of TRAIL expression by ERS was accompanied by a significant decrease in cytokine signaling suppressor 3 (SOCS3). SOCS3 siRNA clearly increased the expression of TRAIL mRNA and protein under ERS by activating the AP‐1 components phosphorylated c‐Jun and phosphorylated c‐Fos in RAW264.7 cells. In contrast, over‐expression of SOCS3 reversed ERS‐induced TRAIL expression. These findings provide in vitro evidence that SOCS3 plays a critical negative role in the regulation of ERS‐induced TRAIL expression via the Jun N‐terminal kinase/AP‐1 signaling pathway in macrophages.
Realised and predicted changes in the invertebrate benthos after restoration of connectivity to the floodplain of a large river
Authors: Castella Emmanuel , Béguin Olga , Besacier‐Monbertrand Anne‐Laure , Hug Peter Dorothea , Lamouroux Nicolas , Mayor Siméant Hélène , McCrae David , Olivier Jean‐Michel , Paillex Amael
Published: April 2015

River–floodplain interactions (i.e. lateral connectivity) are a major driver of the structure and function of the biota in floodplain waterbodies. Therefore, the enhancement of lateral connectivity is a key focus of large river restoration. The Rhône River restoration project in France includes an array of floodplain habitats and restoration measures, offering opportunities to test the predictability of changes in taxon abundance after connectivity restoration.

Quantitative samples of benthic macroinvertebrates taken before restoration were used to derive generalised additive models (GAMs) relating the density of taxa to an index of lateral connectivity. The index combined the diversity of sediment grain size, its organic content, vegetation cover and the water's electrical conductivity. GAMs were used to predict changes in taxon density and between‐site (i.e. beta) diversity 2 and 4 years after restoration at 34 sites (14 unrestored, eight reconnected to the river, six dredged, six restored by increasing river flow).

Observed post‐restoration changes included an increase in the density of rheophilous taxa and an increase of beta‐diversity among restored sites. Fifty‐four GAMs (27% of the taxa) were selected for post‐restoration predictions. Predictions from these models matched observations for a set of Trichoptera and other taxa with large density changes after restoration. The quality of predictions of density changes was poor on average among sites, but higher for sites where large changes in lateral connectivity occurred. Taxon‐level predictions partly explained increased beta‐diversity in restored sites, suggesting that predictions based on a subset of individual taxa can be used to predict community‐level changes.

Our models can guide restoration measures in the Rhône and other rivers. Our results also show the benefit of diversifying restoration actions at the scale of entire floodplains. Post‐restoration trajectories should be monitored over long periods to improve the identification of the key environmental predictors of biotic changes, especially at the less connected floodplain sites.
Interpreting important health‐related quality of life change using the Haem‐A‐QoL
Authors: Wyrwich K. W. , Krishnan S. , Poon J. L. , Auguste P. , von Maltzahn R. , Yu R. , von Mackensen S.
Published: April 2015

The Haemophilia Quality of Life Questionnaire for Adults (Haem‐A‐QoL) measures health‐related quality of life (HRQoL) in adults with haemophilia; however, change score thresholds for identifying individuals experiencing a HRQoL benefit have not been appropriately investigated. The objective of this analysis was to derive appropriate HRQoL responder definitions (RDs) for two Haem‐A‐QoL domains that reflect key impairments, ‘Physical Health’ and ‘Sports & Leisure,’ and the Haem‐A‐QoL ‘Total Score’ using anchor‐ and distribution‐based methods. In this analysis, data from adults in A‐LONG and B‐LONG, two Phase 3 clinical studies of rFVIIIFc in haemophilia A and rFIXFc in haemophilia B, respectively, were used. The anchor‐based approach identified Haem‐A‐QoL changes corresponding to EQ‐5D item improvements between baseline and 6 months; the distribution‐based methods examined the magnitude at baseline of one‐half standard deviation and the standard error of measurement. Through triangulation, the most appropriate RDs were derived. Of the 133 A‐LONG and 73 B‐LONG subjects with baseline Haem‐A‐QoL scores, 67 and 51 subjects, respectively, completed the Haem‐A‐QoL questionnaire at both baseline and 6 months follow‐up. Triangulation of anchor‐ and distribution‐based estimates with the observed Haem‐A‐QoL change scores identified a 10‐point reduction in the ‘Physical Health’ and ‘Sports & Leisure’ domains, and a 7‐point reduction in ‘Total Score’ as the RD thresholds most indicative of HRQoL benefit. These empirically derived RDs for two key Haem‐A‐QoL domains and ‘Total Score’ are reasonable and practical thresholds for identifying subjects with notable improvements in HRQoL, and provides HRQoL RDs that can be used for further analysis and interpretation of data from haemophilia clinical trials.
Clomiphene Citrate as a Preventive Treatment for Intractable Chronic Cluster Headache: A Second Reported Case With Long‐Term Follow‐Up
Authors: Rozen Todd D.
Published: April 2015

Objective

To describe a second case of treatment refractory chronic cluster headache responsive to clomiphene citrate and with long‐term follow‐up.

Methods

Case report with 7‐year evaluation.

Case

A 63‐year‐old man with a 17‐year history of chronic cluster headache preceded to have significant adverse events or was nonresponsive to multiple cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization. The patient experienced 3‐5 headaches per day. On clomiphene citrate 100 mg/day he became 100% pain‐free and remained so for 3.5 years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years with repeat headache recurrence. Clomiphene was restarted, and he became pain‐free once again.

Discussion

This is the second reported case of the effective use of clomiphene citrate for the preventive treatment of medicinal refractory chronic cluster headache. This is the first case to report long‐term follow‐up of this neurohormonal treatment. Clomiphene citrate appears to be safe for extended use in chronic cluster headache even in an elderly sufferer and has a minimal side effect profile. The mechanism of action of how clomiphene prevents cluster headache may involve both its ability to enhance testosterone production and its ability to bind to hypothalamic estrogen receptors. Clomiphene citrate should join the list of alternative cluster headache prophylactic treatments to be considered by headache specialists when conventional cluster headache preventives are ineffective.
Invertebrate prey availability limits reproductive success but not breeding population size in suburban House Sparrows Passer domesticus
Authors: Peach Will J. , Mallord John W. , Ockendon Nancy , Orsman Chris J. , Haines William G.
Published: April 2015

Factors affecting avian demography and abundance in urban landscapes are poorly understood and this hinders attempts to manage urban bird communities. Several recent studies indicate that lack of invertebrate prey in urban landscapes may constrain avian productivity and fitness relative to that in other habitats. House Sparrow Passer domesticus populations have undergone large declines in many European urban centres and inadequate reproductive success linked to invertebrate availability has been postulated as a potential cause of these declines. We conducted a replicated supplementary feeding experiment to test whether the availability of invertebrate prey limits the breeding success and adult abundance (colony size) of House Sparrows in suburban London, where House Sparrow populations declined by 60% during the decade preceding our study. Daily mealworm provision over two successive breeding seasons, sufficient to provide 82% of chick energy requirements of House Sparrow pairs nesting within 50 m of feeders, had a large positive impact on the abundance of recently fledged birds (+62%), but only a small positive impact, limited mainly to small colonies, on the overall abundance of territorial males. Colony growth was only weakly related to fledgling abundance in the previous year and did not appear to be constrained by nest‐site availability. Conservation interventions that enhance invertebrate availability for suburban House Sparrows may increase reproductive success but are unlikely, on their own, to lead to population growth or recovery.
Evaluation of the filling ability of artificial lateral canals using calcium silicate‐based and epoxy resin‐based endodontic sealers and two gutta‐percha filling techniques
Authors: Fernández R. , Restrepo J. S. , Aristizábal D. C. , Álvarez L. G.
Published: April 2015

Aim

To evaluate the ability of a calcium silicate‐based sealer (iRoot SP) and an epoxy resin‐based sealer (Topseal) using two gutta‐percha filling techniques to fill artificial lateral canals (ALCs).

Methodology

Seventy single‐rooted human teeth were selected. Ten of these were used to obtain pilot data. Three ALCs were produced on mesial and distal surfaces of each root, one in each third, using size 10 engine reamers. The roots were randomly assigned to four experimental groups according to the filling technique and sealer used: 1, cold gutta‐percha (single‐point technique) with iRoot SP (SP‐iR); 2, cold gutta‐percha (single‐point technique) with Topseal (SP‐T); 3, continuous wave of condensation technique with iRoot SP (CWC‐iR); and 4, continuous wave of condensation technique with Topseal (CWC‐T). Digital periapical radiographs were taken. After the sealer had set, the roots were demineralized, cleared in methyl‐salicylate and examined under a stereomicroscope. The depth of penetration of sealer and/or gutta‐percha into the ALC was scored using a 5‐point system, conducting an analysis on four surfaces. Filling scores of 0–1 were considered not acceptable, whilst scores of 2–4 were considered acceptable. Pearson′s chi‐square test was used to compare the experimental groups (P < 0.05).

Results

CWC‐T was associated with the highest acceptable filling (57.8%), followed by CWC‐iR (53.3%), SP‐T (48.9%) and SP‐iR (36.7%). Only when SP‐iR was compared to the other groups, was the difference significant (P < 0.05). The apical third was associated with the lowest acceptable filling (37.5%). It was followed, in ascending order, by the middle (51.6%) and coronal thirds (58.3%). These differences were significant only when the apical thirds were compared to the other root thirds (P < 0.05).

Conclusion

The calcium silicate‐based sealer with continuous wave of condensation was more effective in artificial filling lateral canals than the single‐point technique. The epoxy resin‐based sealer with both filling techniques was effective in artificial filling lateral canals.
Preparation of environment‐friendly pectin from sugar beet pulp and assessment of its emulsifying capacity
Authors: Chen Hai‐Ming , Fu Xiong , Abbasi Arshad M. , Luo Zhi‐Gang
Published: April 2015

This study was designed to prepare environment‐friendly pectin from sugar beet pulp (SBP) using subcritical water combined with ultrasonic treatment. Plackett–Burman design based on nineteen different parameters was applied to study the influence of various factors on the characteristics of sugar beet pulp pectin (SBPP). About 29.1% pectin, 62% degree of methylation (DM) and 36% acetylation (DA), and 42.5‐kDa average molecular weight (AMW) were obtained from SBP when using distilled water with solid/liquid ratio of 1:81 for extraction at 110 °C. The yield of SBPP and galacturonic acid (GalA) was mainly affected by solid/liquid (S/L) ratio, water purity and extraction temperature. The ultrasonic temperature, ultrasonic power and extraction temperature were the main factors effecting on neutral sugar content, DM, DA and AMW. Compared with gum arabic (GA), the highest yield SBPP fraction had better emulsifying activity, but poorer emulsion‐stabilizing ability.