bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral venous catheter related complications are common among paediatric and neonatal patients
Authors: Unbeck M , Förberg U , Ygge B‐M , Ehrenberg A , Petzold M , Johansson E 
Published: February 2015

AbstractAimThe aims of this study were to describe the characteristics of peripheral venous catheters (PVCs), including dwell time and reasons for removal, and explore predictors for PVC‐related complications.MethodsWe included PVCs in 2032 children – 484 neonatal and 1548 paediatric – from 12 inpatient units. Data were retrieved from the patient record system, and predictors for complications were explored using logistic regression analyses.ResultsJust over one‐third (35.4%) of the PVCs were removed due to complications, in particular infiltration and occlusion (51.9 and 48.4/1000 PVC days, respectively). PVC survival time was shorter in neonatal than paediatric patients (4 versus 5 days), and infiltration was more frequent in neonatal patients (92.8 versus 38.7/1000 PVC days). Infiltration was associated with younger age (odds ratio 0.97) for neonatal patients and with younger age (OR 0.96), insertion in the bend of the arm (OR 1.48) or ankle (OR 2.81) for paediatric patients. Occlusion was, both for neonatal and paediatric patients, associated with longer dwell time (OR 1.32 and 1.22 respectively), insertion in the ankle (OR 5.00 and 3.51) or foot (OR 3.47 and 1.99).ConclusionPVC‐related complications, particularly infiltration and occlusion, were more common in hospitalised children but decreased with the child's age.
Updated Swedish advice on reducing the risk of sudden infant death syndrome
Authors: Wennergren Göran , Nordstrand Kerstin , Alm Bernt , Möllborg Per , Öhman Anna , Berlin Anita , Katz‐Salamon Miriam , Lagercrantz Hugo 
Published: February 2015

AbstractThis article reviews updated advice and factual material from the Swedish National Board of Health and Welfare on reducing the risk of sudden infant death syndrome. Issues covered by the guidance for parents and healthcare professionals include sleeping positions, smoking, breastfeeding, bed sharing and using pacifiers.ConclusionThe guidelines conclude that infants under three months of age are safest sleeping in their own cot and that a pacifier can be used when they are going to sleep.
Systematic review with meta‐analysis: the efficacy of a second anti‐TNF in patients with inflammatory bowel disease whose previous anti‐TNF treatment has failed
Authors: Gisbert J. P. , Marín A. C. , McNicholl A. G. , Chaparro M. 
Published: February 2015

SummaryBackgroundOne‐third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti‐TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.AimTo investigate the efficacy and safety of a second anti‐TNF agent after primary/secondary failure or intolerance to a first drug.MethodsInclusion criteria: studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab‐pegol (CZP) as the second anti‐TNF in CD or UC. Search strategy: Bibliographical searches (PubMed/Embase). Data synthesis: percentage of response/remission; the meta‐analysis was performed using the inverse variance method.ResultsWe included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFX→ADA, 4 IFX→CZP and 1 ADA→IFX. Overall, the second anti‐TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti‐TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFX→ADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0–21%, discontinuation rate <20%).ConclusionsThe efficacy of a second anti‐TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti‐TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADA→IFX are needed to evaluate this strategy. PROSPERO‐registry‐number: CRD42014012943.
Effect and Placental Transfer of Dexmedetomidine During Caesarean Section Under General Anaesthesia
Authors: Yu Min , Han Chuanbao , Jiang Xiuhong , Wu Xia , Yu Li , Ding Zhengnian 
Published: February 2015

AbstractMany drugs can pass through the placenta and cause adverse effects on the foetus. Thus, during Caesarean section for puerperas who have contraindications for intravertebral anaesthesia, the use of proper drugs that have sedative, analgesic effects on the puerperas without adverse effects on the foetus is important. In this study, we investigated the effect and placental transfer of dexmedetomidine during Caesarean section under general anaesthesia. Thirty‐eight puerperas were randomly divided to receive dexmedetomidine or saline before anaesthesia induction and during the operation. The dexmedetomidine‐treated parturients had lower mean arterial pressure and heart rate at the delivery and at the end of the operation. The dexmedetomidine‐treated parturients also needed 5.5% less propofol and 8.4% less fentanyl than the saline‐treated ones. Between the dexmedetomidine‐treated and saline‐treated parturients, there was no difference in the maternal artery, umbilical vein, umbilical artery blood gas analysis results and the Apgar scores at 1 and 5 min. after delivery. The placental transfer rate of dexmedetomidine was 0.76. We concluded that dexmedetomidine was effective in maintaining the haemodynamic stability in the parturients during Caesarean section under general anaesthesia without adverse neonatal effects. Dexmedetomidine can pass through the placenta with a placental transfer rate of 0.76.
HuR mediates the synergistic effects of angiotensin II and IL‐1β on vascular COX‐2 expression and cell migration
Authors: Aguado A , Rodríguez C , Martínez‐Revelles S , Avendaño M S , Zhenyukh O , Orriols M , Martínez‐González J , Alonso M J , Briones A M , Dixon D A , Salaices M 
Published: February 2015

Background and PurposeAngiotensin II (AngII) and IL‐1β are involved in cardiovascular diseases through the induction of inflammatory pathways. HuR is an adenylate‐ and uridylate‐rich element (ARE)‐binding protein involved in the mRNA stabilization of many genes. This study investigated the contribution of HuR to the increased expression of COX‐2 induced by AngII and IL‐1β and its consequences on VSMC migration and remodelling.Experimental ApproachRat and human VSMCs were stimulated with AngII (0.1 μM) and/or IL‐1β (10 ng·mL−1). Mice were infused with AngII or subjected to carotid artery ligation. mRNA and protein levels were assayed by quantitative PCR, Western blot, immunohistochemistry and immunofluorescence. Cell migration was measured by wound healing and transwell assays.Key ResultsIn VSMCs, AngII potentiated COX‐2 and tenascin‐C expressions and cell migration induced by IL‐1β. This effect of AngII on IL‐1β‐induced COX‐2 expression was accompanied by increased COX‐2 3′ untranslated region reporter activity and mRNA stability, mediated through cytoplasmic HuR translocation and COX‐2 mRNA binding. These effects were blocked by ERK1/2 and HuR inhibitors. VSMC migration was reduced by blockade of ERK1/2, HuR, COX‐2, TXAS, TP and EP receptors. HuR, COX‐2, mPGES‐1 and TXAS expressions were increased in AngII‐infused mouse aortas and in carotid‐ligated arteries. AngII‐induced tenascin‐C expression and vascular remodelling were abolished by celecoxib and by mPGES‐1 deletion.Conclusions and ImplicationsThe synergistic induction of COX‐2 by AngII and IL‐1β in VSMCs involves HuR through an ERK1/2‐dependent mechanism. The HuR/COX‐2 axis participates in cell migration and vascular damage. HuR might be a novel target to modulate vascular remodelling.
A store‐operated calcium channel inhibitor attenuates collagen‐induced arthritis
Authors: Gao X H , Gao R , Tian Y Z , McGonigle P , Barrett J E , Dai Y , Hu H 
Published: February 2015

Background and PurposeStore‐operated calcium (SOC) channels are thought to play a critical role in immune responses, inflammatory diseases and chronic pain. The aim of this study was to explore the potential role and mechanisms of SOC channels in collagen‐induced arthritis (CIA).Experimental ApproachThe CIA mouse model was used to examine the effects of the SOC channel inhibitor YM‐58483 on CIA and arthritic pain. Hargreaves' and von Frey hair tests were conducted to measure thermal and mechanical sensitivities of hind paws. elisa was performed to measure cytokine production, and haematoxylin and eosin staining was used to assess knee histological changes. Western blot analysis was performed to examine protein levels.Key ResultsPretreatment with 5 or 10 mg·kg−1 of YM‐58483 reduced the incidence of CIA, prevented the development of inflammation and pain hypersensitivity and other signs and features of arthritis disease. Similarly, treatment with YM‐58483 after the onset of CIA: (i) reversed the clinical scores; (ii) reduced paw oedema; (iii) attenuated mechanical and thermal hypersensitivity; (iv) improved spontaneous motor activity; (v) decreased periphery production of IL‐1β, IL‐6 and TNF‐α; and (vi) reduced spinal activation of ERK and calmodulin‐dependent PKII (CaMKIIα).Conclusions and ImplicationsThis study provides the first evidence that inhibition of SOC entry prevents and relieves rheumatoid arthritis (RA) and arthritic pain. These effects are probably mediated by a reduction in cytokine levels in the periphery and activation of ERK and CaMKIIα in the spinal cord. These results suggest that SOC channels are potential drug targets for the treatment of RA.
Class A1 scavenger receptors in cardiovascular diseases
Authors: Ben Jingjing , Zhu Xudong , Zhang Hanwen , Chen Qi 
Published: February 2015

Class A1 scavenger receptors (SR‐A1) are membrane glycoproteins that can form homotrimers. This receptor was originally defined by its ability to mediate the accumulation of lipids in macrophages. Subsequent studies reveal that SR‐A1 plays critical roles in innate immunity, cell apoptosis and proliferation. This review highlights recent advances in understanding the structure, receptor pathway and regulation of SR‐A1. Although its role in atherosclerosis is disputable, recent discoveries suggest that SR‐A1 function in anti‐inflammatory responses by promoting an M2 macrophage phenotype in cardiovascular diseases. Therefore, SR‐A1 may be a potential target for therapeutic intervention of cardiovascular diseases.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
The GPR55 agonist lysophosphatidylinositol relaxes rat mesenteric resistance artery and induces Ca2+ release in rat mesenteric artery endothelial cells
Authors: AlSuleimani Y M , Hiley C R 
Published: February 2015

Background and PurposeLysophosphatidylinositol (LPI), a lipid signalling molecule, activates GPR55 and elevates intracellular Ca2+. Here, we examine the actions of LPI in the rat resistance mesenteric artery and Ca2+ responses in endothelial cells isolated from the artery.Experimental ApproachVascular responses were studied using wire myographs. Single‐cell fluorescence imaging was performed using a MetaFluor system. Hypotensive effects of LPI were assessed using a Biopac system.Key ResultsIn isolated arteries, LPI‐induced vasorelaxation was concentration‐ and endothelium‐dependent and inhibited by CID 16020046, a GPR55 antagonist. The CB1 receptor antagonist AM 251 had no effect, whereas rimonabant and O‐1918 significantly potentiated LPI responses. Vasorelaxation was reduced by charybdotoxin and iberiotoxin, alone or combined. LPI decreased systemic arterial pressure. GPR55 is expressed in rat mesenteric artery. LPI caused biphasic elevations of endothelial cell intracellular Ca2+. Pretreatment with thapsigargin or 2‐aminoethoxydiphenyl borate abolished both phases. The PLC inhibitor U73122 attenuated the initial phase and enhanced the second phase, whereas the Rho‐associated kinase inhibitor Y‐27632 abolished the late phase but not the early phase .Conclusions and ImplicationsLPI is an endothelium‐dependent vasodilator in the rat small mesenteric artery and a hypotensive agent. The vascular response involves activation of Ca2+‐sensitive K+ channels and is not mediated by CB1 receptors, but unexpectedly enhanced by antagonists of the ‘endothelial anandamide’ receptor. In endothelial cells, LPI utilizes PLC‐IP3 and perhaps ROCK‐RhoA pathways to elevate intracellular Ca2+. Overall, these findings support an endothelial site of action for LPI and suggest a possible role for GPR55 in vasculature.
Kaempferol enhances endothelium‐dependent relaxation in the porcine coronary artery through activation of large‐conductance Ca2+‐activated K+ channels
Authors: Xu Y C , Leung S W S , Leung G P H , Man R Y K 
Published: February 2015

Background and PurposeKaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle.Experimental ApproachThe effect of kaempferol on the relaxation of porcine coronary arteries to endothelium‐dependent (bradykinin) and ‐independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole‐cell patch‐clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs).Key ResultsAt a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin‐induced relaxation was not affected by Nω‐nitro‐L‐arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM‐34 plus UCL 1684, inhibitors of intermediate‐ and small‐conductance calcium‐activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non‐selective inhibitor of calcium‐activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large‐conductance calcium‐activated potassium channel (KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside‐induced relaxations. Kaempferol stimulated an outward‐rectifying current in PCASMCs, which was abolished by iberiotoxin.Conclusions and ImplicationsThe present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium‐derived and exogenous NO as well as those due to endothelium‐dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels.
NeuroD1 promotes neuroblastoma cell growth by inducing the expression of ALK
Authors: Lu Fangjin , Kishida Satoshi , Mu Ping , Huang Peng , Cao Dongliang , Tsubota Shoma , Kadomatsu Kenji 
Published: February 2015

Neuroblastoma is derived from the sympathetic neuronal lineage of neural crest cells, and is the most frequently observed of the extracranial pediatric solid tumors. The neuronal differentiation factor, NeuroD1, has previously been shown to promote cell motility in neuroblastoma by suppressing the expression of Slit2. Here we report that NeuroD1 is also involved in the proliferation of neuroblastoma cells, including human cell lines and primary tumorspheres cultured from the tumor tissues of model mice. Interestingly, the growth inhibition of neuroblastoma cells induced by knockdown of NeuroD1 was accompanied by a reduction of ALK expression. ALK is known to be one of the important predisposition genes for neuroblastoma. The phenotype resulting from knockdown of NeuroD1 was suppressed by forced expression of ALK and, therefore, NeuroD1 appears to act mainly through ALK to promote the proliferation of neuroblastoma cells. Furthermore, we showed that NeuroD1 directly bound to the promoter region of ALK gene. In addition, the particular E‐box in the promoter was responsible for NeuroD1‐mediated ALK expression. These results indicate that ALK should be a direct target gene of NeuroD1. Finally, the expressions of NeuroD1 and ALK in the early tumor lesions of neuroblastoma model mice coincided in vivo. We conclude that the novel mechanism would regulate the expression of ALK in neuroblastoma and that NeuroD1 should be significantly involved in neuroblastoma tumorigenesis.
The emergent geography of biophysical dispersal barriers across the Indo‐West Pacific
Authors: Treml Eric A. , Roberts Jason , Halpin Patrick N. , Possingham Hugh P. , Riginos Cynthia 
Published: February 2015

AbstractAimTo discover and evaluate potential dispersal barriers across the Indo‐West Pacific Ocean and to develop spatially explicit hypotheses regarding the location of barriers and their capacity to filter taxa. Additionally, to compare model predictions with previously described barriers and build a more thorough understanding of the region's biogeographic patterns.LocationThe reefs of the Indo‐West Pacific Ocean, from 100 to 170°E and from 30°N to 30°S.MethodsA biophysical larval dispersal model was used to quantify over 800,000 dispersal kernels by simulating 99 model taxa. Spatial analysis was used to map emergent patterns of potential multispecies population connectivity and predict geographic locations and strength of concordant dispersal barriers across the seascape.ResultsAlthough individual taxa varied in their predicted fine‐scale population connectivity, there was consistency in the location of dispersal barriers. Across all trait combinations, reproductive output (fecundity and density of reproductive adults), reproductive strategy (spawning phenology) and the length of the larval dispersal phase determined the strength of barriers across the seascape. More than 80% of the previously described marine boundaries in the region were predicted to restrict the dispersal of at least 10% of the simulated taxa. The location and strength of many additional multitaxa barriers were described at scales <200 km.Main conclusionsThe geographic structure of many previously described multispecies barriers across the Indo‐West Pacific were predicted with the biophysical dispersal model and spatial analysis. The permeability of individual dispersal barriers was primarily determined by reproductive output, spawning phenology and the length of the pelagic larval stage. Across all dispersal barriers analysed, Euclidean distance explained up to 49% of the variation in barrier strength.
Impact of treatment with saxagliptin on glycaemic stability and β‐cell function in the SAVOR‐TIMI 53 study
Authors: Leibowitz G. , Cahn A. , Bhatt D. L. , Hirshberg B. , Mosenzon O. , Wei C. , Jermendy G. , Sheu W. H.‐H. , Sendon J. L. , Im K. , Braunwald E. , Scirica B. M. , Raz I. 
Published: February 2015

AimsTo study the effects of saxagliptin, a dipeptidyl peptidase‐4 inhibitor, on glycaemic stability and β‐cell function in the SAVOR‐TIMI 53 trial.MethodsWe randomized 16 492 patients with type 2 diabetes (T2D) to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of ≥0.5% post‐randomization; (ii) the initiation of new antidiabetic medications for ≥3 months; or (iii) an increase in dose of oral antidiabetic medication or ≥25% increase in insulin dose for ≥3 months. β‐cell function was assessed according to fasting homeostatic model 2 assessment of β‐cell function (HOMA‐2β) values at baseline and at year 2 in patients not treated with insulin.ResultsCompared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68–0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of ≥0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA‐2β values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001).ConclusionsSaxagliptin improved glycaemia and prevented the reduction in HOMA‐2β values. Saxagliptin may reduce the usual decline in β‐cell function in T2D, thereby slowing diabetes progression.
Chemical genomics approach to identify genes associated with sensitivity to rapamycin in the fission yeast Schizosaccharomyces pombe
Authors: Doi Akira , Fujimoto Ayumi , Sato Shun , Uno Takaya , Kanda Yuki , Asami Keita , Tanaka Yuriko , Kita Ayako , Satoh Ryosuke , Sugiura Reiko 
Published: February 2015

Rapamycin and its derivatives have now emerged as an attractive therapeutic strategy with both immunosuppressant and antitumor properties. In addition, rapamycin has been proposed as a calorie restriction mimetic to extend the life span of various organisms. The fission yeast Schizosaccharomyces pombe (S. pombe) serves as a valuable genetic model system to study the mechanism(s) of drug action as well as to determine genetic contexts associated with drug sensitivity or resistance. Here, we identified genes that when deleted modulate the rapamycin‐sensitive strains in S. pombe. We carried out a chemical genomics screen for rapamycin‐sensitive mutants using the genome‐deletion library which covers 95.3% of all nonessential fission yeast genes and confirmed 59 genes to be rapamycin sensitive. Gene Ontology (GO) enrichment analysis showed that strains sensitive to rapamycin are highly enriched in processes regulating tRNA modification and mitochondria as well as other ontologies, including cellular metabolic process, chromatin organization, cell cycle, signaling, translation, transport and other cellular processes. Analysis also showed that components of the Elongator complex are overrepresented in the sensitive strains. Here, the data obtained will provide valuable information for speculation on the actions of rapamycin as well as on TORC signaling, thereby presenting a strategy to enhance sensitivity to rapamycin.