bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety issues with glucagon‐like peptide‐1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): Data from randomized controlled trials
Authors: Monami Matteo , Nreu Besmir , Scatena Alessia , Cresci Barbara , Andreozzi Francesco , Sesti Giorgio , Mannucci Edoardo 
Published: February 2017

AimGlucagon‐like peptide 1 receptor agonists (GLP1‐RA) have been associated with an increased risk of pancreatitis and pancreatic cancer. Prior meta‐analyses of randomized controlled trials failed to show any significant increase of risk; however, those meta‐analyses did not include the recently published cardiovascular outcome trials (CVOT) with GLP1‐RA, which provide a substantial additional body of data. The aim of the present meta‐analysis is to assess the effect of GLP1‐RA on pancreatitis, pancreatic cancers and cholelithiasis.Materials and methodsA Medline search for GLP‐1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide or semaglutide) was performed, collecting all randomized clinical trials with a duration >11 weeks, enrolling patients with type 2 diabetes and comparing a GLP‐1 receptor agonist with placebo or any other non‐GLP‐1 receptor agonist drug.ResultsOf the 113 trials fulfilling inclusion criteria, 13 did not report information on pancreatitis, whereas 72 reported no events in all treatment groups. The incidence of pancreatitis and pancreatic cancer with GLP1‐RA was not significantly different from that observed in comparator arms (MH‐OR [95% CI] 0.93 [0.65‐1.34], P = .71, and 0.94 [0.52‐1.70], P = .84, respectively), whereas, a significantly increased risk of cholelithiasis (MH‐OR [95% CI] 1.30 [1.01‐1.68], P = .041) was detected.ConclusionsPresently available data confirm the safety of GLP‐1 receptor agonists for pancreatitis. Conversely, therapy with those drugs is associated with an increased risk of cholelithiasis, which deserves further investigation.
Glycogen synthase kinase 3 regulates photic signaling in the suprachiasmatic nucleus
Authors: Paul Jodi R. , McKeown Alex S. , Davis Jennifer A. , Totsch Stacie K. , Mintz Eric M. , Kraft Timothy W. , Cowell Rita M. , Gamble Karen L. 
Published: February 2017

AbstractGlycogen synthase kinase 3 (GSK3) is a serine‐threonine kinase that regulates mammalian circadian rhythms at the behavioral, molecular and neurophysiological levels. In the central circadian pacemaker, the suprachiasmatic nucleus (SCN), inhibitory phosphorylation of GSK3 exhibits a rhythm across the 24 h day. We have recently shown that GSK3 is capable of influencing both the molecular clock and SCN neuronal activity rhythms. However, it is not known whether GSK3 regulates the response to environmental cues such as light. The goal of this study was to test the hypothesis that GSK3 activation mediates light‐induced SCN excitability and photic entrainment. Immunofluorescence staining in the SCN of mice showed that late‐night light exposure significantly increased GSK3 activity (decreased pGSK3β levels) 30–60 min after the light‐pulse. In addition, pharmacological inhibition of GSK3 blocked the expected light‐induced excitability in SCN neurons; however, this effect was not associated with changes in resting membrane potential or input resistance. Behaviorally, mice with constitutively active GSK3 (GSK3‐KI) re‐entrained to a 6‐h phase advance in the light‐dark cycle in significantly fewer days than WT control animals. Furthermore, the behavioral and SCN neuronal activity of GSK3‐KI mice was phase‐advanced compared to WT, in both normal and light‐exposed conditions. Finally, GSK3‐KI mice exhibited normal negative‐masking behavior and electroretinographic responses to light, suggesting that the enhanced photic entrainment is not due to an overall increased sensitivity to light in these animals. Taken together, these results provide strong evidence that GSK3 activation contributes to light‐induced phase‐resetting at both the neurophysiological and behavioral levels.
Chemogenetic enhancement of functional recovery after a sciatic nerve injury
Authors: Jaiswal Poonam B. , English Arthur W. 
Published: February 2017

AbstractDesigner receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools used to modulate neuronal excitability. We hypothesized that activation of excitatory (Gq) DREADD by its designer ligand, clozapine‐N‐oxide (CNO), would increase the excitability of neurons whose axons have been transected following peripheral nerve injury, and that this increase will lead to an enhanced functional recovery. The lateral gastrocnemius (LG) muscle of adult female Lewis rats was injected unilaterally with AAV9‐ hsyn‐ hM3Dq‐mCherry (7.6 × 109 viral genomes/μL) to transduce Gq‐DREADD expression in LG neurons. The contralateral LG muscle served as an uninjected control. No significant changes in either spontaneous EMG activity or electrically evoked direct muscle (M) responses were found in either muscle after injection of CNO (1 mg/kg, i.p.). The amplitude of monosynaptic H‐reflexes in LG was increased after CNO treatment exclusively in muscles previously injected with virus, suggesting that Gq‐DREADD activation increased neuronal excitability. After bilateral sciatic nerve transection and repair, additional rats were treated similarly with CNO for up to three days after injury. Electrophysiological data were collected at 2, 4 and 6 weeks after injury. Evoked EMG responses were observed as early as 2 weeks after injury only in Gq‐DREADD expressing virus injected LG muscle. By 4 weeks after injury, both M‐response and H‐reflex amplitudes were significantly greater in muscles previously injected with viral vector than contralateral, uninjected muscles. Increases in the excitability of injured neurons produced by this novel use of Gq‐DREADD were sufficient to promote an enhancement in functional recovery after a sciatic nerve injury.
NF‐κB signalling is involved in immune‐modulation, but not basal functioning, of the mouse suprachiasmatic circadian clock
Authors: O'Keeffe S. M. , Beynon A. L. , Davies J. S. , Moynagh P. N. , Coogan A. N. 
Published: February 2017

AbstractCircadian rhythms are recurring near‐24 hour patterns driven by an endogenous circadian timekeeping system. The master pacemaker in this system is the hypothalamic suprachiasmatic nucleus (SCN). Recently interest has been drawn to how the SCN clock responds to immune system stimulation. A major signalling component in the immune system is nuclear factor (NF)‐κB. In the present study we examined the role of NF‐κB in SCN function. Whilst serum shocked fibroblasts showed rhythmic nuclear localisation of p65 and p65‐dependent transcription, there were no circadian changes in the SCN in expression of the NF‐κB components p65, c‐Rel, p‐IκB or p‐IKK. Chronic treatment with the NF‐κB inhibitor PDTC did not impact on circadian or diurnal rhythms. Phase‐shifting light pulses did not impact on SCN expression of p65, and PDTC treatment did not attenuate the behavioural or molecular response to light pulses. Peripheral treatment with lipopolysaccharide resulted in increased NF‐κB component expression in the SCN. In vitro experiments with SCN slice cultures showed that treatment with NF‐κB inhibitors did not markedly alter rhythmic changes in PER2::LUC expression. Further, SCN slices from nf‐κb::luc mice did not show any evidence for circadian rhythms in NF‐κB‐mediated transcription. Experiments utilising older mice (~16 months old) showed that SCN treatment in vitro with PDTC resulted in increased amplitude of rhythmic PER2::LUC expression, and LPS treatment resulted in altered PER2::LUC rhythm acrophase. Overall, we interpret our results as providing evidence for the involvement of NF‐κB in the suprachiasmatic circadian clock following immune stimulation, but not under basal conditions.
Effect on cardiovascular disease risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes: A systematic review and meta‐analysis of trials in primary care
Authors: Dambha‐Miller Hajira , Cooper Andrew J. M. , Kinmonth Ann Louise , Griffin Simon J. 
Published: February 2017

AbstractObjectiveTo examine the effect on cardiovascular (CVD) risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes.Search StrategyElectronic and manual citation searching to identify relevant randomized controlled trials (RCTs).Inclusion CriteriaRCTs that compared usual care to interventions to alter consultations between practitioners and patients. The population was adults aged over 18 years with type 2 diabetes. Trials were set in primary care.Data extraction and synthesisWe recorded if explicit theory‐based interventions were used, how consultations were measured to determine whether interventions had an effect on these and calculated weighted mean differences for CVD risk factors including glycated haemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), LDL cholesterol (LDL‐C) and HDL cholesterol (HDL‐C).ResultsWe included seven RCTs with a total of 2277 patients with type 2 diabetes. A range of measures of the consultation was reported, and underlying theory to explain intervention processes was generally undeveloped and poorly applied. There were no overall effects on CVD risk factors; however, trials were heterogeneous. Subgroup analysis suggested some benefit among studies in which interventions demonstrated impact on consultations; statistically significant reductions in HbA1c levels (weighted mean difference, −0.53%; 95% CI: [−0.77, −0.28]; P<.0001; I2=46%).ConclusionsEvidence of effect on CVD risk factors from interventions to alter consultations between practitioners and patients with type 2 diabetes was heterogeneous and inconclusive. This could be explained by variable impact of interventions on consultations. More research is required that includes robust measures of the consultations and better development of theory to elucidate mechanisms.
Acute Cardiac MRI Assessment of Radiofrequency Ablation Lesions for Pediatric Ventricular Arrhythmia: Feasibility and Clinical Correlation
Authors: GRANT ELENA K. , BERUL CHARLES I. , CROSS RUSSELL R. , MOAK JEFFREY P. , HAMANN KARIN S. , SUMIHARA KOHEI , CRONIN ILEEN , O'BRIEN KENDALL J. , RATNAYAKA KANISHKA , HANSEN MICHAEL S. , KELLMAN PETER , OLIVIERI LAURA J. 
Published: February 2017

Acute Pediatric VT Ablation Cardiac MRI AssessmentBackgroundArrhythmia ablation with current techniques is not universally successful. Inadequate ablation lesion formation may be responsible for some arrhythmia recurrences. Periprocedural visualization of ablation lesions may identify inadequate lesions and gaps to guide further ablation and reduce risk of arrhythmia recurrence.MethodsThis feasibility study assessed acute postprocedure ablation lesions by MRI, and correlated these findings with clinical outcomes. Ten pediatric patients who underwent ventricular tachycardia ablation were transferred immediately postablation to a 1.5T MRI scanner and late gadolinium enhancement (LGE) imaging was performed to characterize ablation lesions. Immediate and mid‐term arrhythmia recurrences were assessed.ResultsPatient characteristics include median age 14 years (1–18 years), median weight 52 kg (11–81 kg), normal cardiac anatomy (n = 6), d‐transposition of great arteries post arterial switch repair (n = 2), anomalous coronary artery origin post repair (n = 1), and cardiac rhabdomyoma (n = 1). All patients underwent radiofrequency catheter ablation of ventricular arrhythmia with acute procedural success. LGE was identified at the reported ablation site in 9/10 patients, all arrhythmia‐free at median 7 months follow‐up. LGE was not visible in 1 patient who had recurrence of frequent premature ventricular contractions within 2 hours, confirmed on Holter at 1 and 21 months post procedure.ConclusionsVentricular ablation lesion visibility by MRI in the acute post procedure setting is feasible. Lesions identifiable with MRI may correlate with clinical outcomes. Acute MRI identification of gaps or inadequate lesions may provide the unique temporal opportunity for additional ablation therapy to decrease arrhythmia recurrence.
Predictive value of plasma copeptin level for the risk and mortality of heart failure: a meta‐analysis
Authors: Yan Jian‐Jun , Lu Ying , Kuai Zheng‐Ping , Yong Yong‐Hong 
Published: February 2017

AbstractEpidemiologic studies are inconsistent regarding the association between plasma copeptin level and heart failure (HF). The aim of this study was to perform a meta‐analysis to determine whether high level of copeptin is correlated with incidence of HF and mortality in patients with HF. We searched PUBMED and EMBASE databases for studies conducted from 1966 through May 2016 to identify studies reporting hazard ratio (HR) estimates with 95% confidence intervals (CIs) for the association between plasma copeptin level and HF. A random‐effects model was used to combine study‐specific risk estimates. A total of 13 studies were included in the meta‐analysis, with five studies on the incidence of HF and eight studies on the mortality of patients with HF. For incidence of HF, the summary HR indicated a borderline positive association of high plasma copeptin level with HF risk (HR, 1.60; 95% CI, 0.90–2.85). Furthermore, an increase of 1 standard deviation in log copeptin level was associated with a 17% increase in the risk of incident HF (HR, 1.17; 95% CI, 1.02–1.33). For all‐cause mortality of patients with HF, we also found a significant association between elevated plasma copeptin level and increased mortality of HF (HR, 1.76; 95% CI, 1.33–2.33). Our dose–response analysis indicated that an increment in copeptin level of 1 pmol/l was associated with a 3% increase in all‐cause mortality (HR, 1.03; 95% CI, 1.01–1.05). In conclusion, our results suggest that elevated plasma copeptin level is associated with an increased risk of HF and all‐cause mortality in patients with HF.
Salvianolic acid B regulates gene expression and promotes cell viability in chondrocytes
Authors: Yang Xiaohong , Liu Shaojie , Li Siming , Wang Pengzhen , Zhu Weicong , Liang Peihong , Tan Jianrong , Cui Shuliang 
Published: February 2017

AbstractArticular chondrocytes reside in lacunae distributed in cartilage responsible for the remodelling of the tissue with limited ability of damage repairing. The in vitro expanded chondrocytes enhanced by factors/agents to obtain large numbers of cells with strengthened phenotype are essential for successful repair of cartilage lesions by clinical cell implantation therapies. Because the salvianolic acid B (Sal B), a major hydrophilic therapeutic agent isolated from Salvia miltiorrhiza, has been widely used to treat diseases and able to stimulate activity of cells, this study examines the effects of Sal B on passaged chondrocytes. Chondrocytes were treated with various concentrations of Sal B in monolayer culture, their morphological properties and changes, and mitochondrial membrane potential were analysed using microscopic analyses, including cellular biochemical staining and confocal laser scanning microscopy. The proteins were quantified by BCA and Western blotting, and the transcription of genes was detected by qRT‐PCR. The passaged chondrocytes treated with Sal B showed strengthened cellular synthesis and stabilized mitochondrial membrane potential with upregulated expression of the marker genes for chondrocyte phenotype, Col2‐α1, Acan and Sox9, the key Wnt signalling molecule β‐catenin and paracrine cytokine Cytl‐1. The treatments using CYTL‐1 protein significantly increased expression of Col2‐α1 and Acan with no effect on Sox9, indicating the paracrine cytokine acts on chondrocytes independent of SOX9. Sal B has ultimately promoted cell growth and enhanced chondrocyte phenotype. The chondrocytes treated with pharmaceutical agent and cytokine in the formulated medium for generating large number of differentiated chondrocytes would facilitate the cell‐based therapies for cartilage repair.
Peripheral viral challenge elevates extracellular glutamate in the hippocampus leading to seizure hypersusceptibility
Authors: Hunsberger Holly C. , Konat Gregory W. , Reed Miranda N. 
Published: February 2017

AbstractPeripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that the acute phase response instigated by an intraperitoneal (i.p.) injection of a viral mimetic, polyinosinic‐polycytidylic acid (PIC), induces protracted hypersusceptibility to kainic acid‐induced seizures. We have further demonstrated that PIC challenge robustly increases the level of tonic extracellular glutamate and neuronal excitability in the hippocampus. This study was undertaken to determine a relationship between tonic glutamate and seizure susceptibility following PIC challenge. Briefly, glutamate‐sensing microelectrodes were permanently implanted into the CA1 of 8‐week‐old female C57BL/6 mice. Following a 3‐day recovery, acute phase response was induced by i.p. injection of 12 mg/kg of PIC, while saline‐injected mice served as controls. Tonic glutamate was measured at 1, 2, 3 and 4 days after PIC challenge. PIC challenge induced an approximately fourfold increase in tonic glutamate levels measured after 24 h. The levels gradually declined to the baseline values within 4 days. Twenty‐four hours after PIC challenge, the mice featured an approximately threefold increase in cumulative seizure scores and twofold increase in the duration of status epilepticus induced by subcutaneous injection of 12 mg/kg of kainic acid. Seizure scores positively correlated with pre‐seizure tonic glutamate. Moreover, seizures resulted in a profound (76%) elevation of extracellular glutamate in the CA1 of PIC‐challenged but not saline‐injected mice. Our results implicate the increase in extracellular glutamate as a mediator of seizure hypersusceptibility induced by peripheral viral challenge.
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Do foreign workers reduce trade barriers? Microeconomic evidence
Authors: Andrews Martyn , Schank Thorsten , Upward Richard 
Published: February 2017

AbstractThis paper provides evidence that foreign workers reduce firms’ trade costs and thus increase the probability that firms export. This informs both the literature on trade costs and the microeconomic literature on firms’ export behaviour. We identify the nationality of each worker in a large sample of German establishments and relate this to the exporting behaviour of these establishments. We allow for the possible endogeneity of an establishment's workforce by instrumenting the share of foreign workers with the regional distribution of foreign workers in the wider labour market. We find a significant effect of worker nationality on exporting which is not driven by the industrial, occupational or locational concentration of migrants. The effect is much stronger for senior occupations, who are more likely to have a role in exporting decisions by the establishment. The relationship is also stronger when we consider exports to particular regions and workers from these regions, consistent with a gravity model in which trade flows from country i to j are a function of migrants from j in i.
Feasibility of using respiration‐averaged MR images for attenuation correction of cardiac PET/MR imaging
Authors: Ai Hua , Pan Tinsu 
Published: February 2017

Cardiac imaging is a promising application for combined PET/MR imaging. However, current MR imaging protocols for whole‐body attenuation correction can produce spatial mismatch between PET and MR‐derived attenuation data owing to a disparity between the two modalities' imaging speeds. We assessed the feasibility of using a respiration‐averaged MR (AMR) method for attenuation correction of cardiac PET data in PET/MR images. First, to demonstrate the feasibility of motion imaging with MR, we used a 3T MR system and a two‐dimensional fast spoiled gradient‐recalled echo (SPGR) sequence to obtain AMR images of a moving phantom. Then, we used the same sequence to obtain AMR images of a patient's thorax under free‐breathing conditions. MR images were converted into PET attenuation maps using a three‐class tissue segmentation method with two sets of predetermined CT numbers, one calculated from the patient‐specific (PS) CT images and the other from a reference group (RG) containing 54 patient CT datasets. The MR‐derived attenuation images were then used for attenuation correction of the cardiac PET data, which were compared to the PET data corrected with average CT (ACT) images. In the myocardium, the voxel‐by‐voxel differences and the differences in mean slice activity between the AMR‐corrected PET data and the ACT‐corrected PET data were found to be small (less than 7%). The use of AMR‐derived attenuation images in place of ACT images for attenuation correction did not affect the summed stress score. These results demonstrate the feasibility of using the proposed SPGR‐based MR imaging protocol to obtain patient AMR images and using those images for cardiac PET attenuation correction. Additional studies with more clinical data are warranted to further evaluate the method.PACS number: 87.57.uk
AAPM/SNMMI Joint Task Force: report on the current state of nuclear medicine physics training
Authors: Harkness Beth A. , Allison Jerry D. , Clements Jessica B. , Coffey Charles W. , Fahey Frederic H. , Gress Dustin A. , Kinahan Paul E. , Nickoloff Edward L. , Mawlawi Osama R. , MacDougall Robert D. , Pizzuitello Robert J. 
Published: February 2017

The American Association of Physicists in Medicine (AAPM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recognized the need for a review of the current state of nuclear medicine physics training and the need to explore pathways for improving nuclear medicine physics training opportunities. For these reasons, the two organizations formed a joint AAPM/SNMMI Ad Hoc Task Force on Nuclear Medicine Physics Training. The mission of this task force was to assemble a representative group of stakeholders to:

Estimate the demand for board‐certified nuclear medicine physicists in the next 5–10 years,
Identify the critical issues related to supplying an adequate number of physicists who have received the appropriate level of training in nuclear medicine physics, and
Identify approaches that may be considered to facilitate the training of nuclear medicine physicists.As a result, a task force was appointed and chaired by an active member of both organizations that included representation from the AAPM, SNMMI, the American Board of Radiology (ABR), the American Board of Science in Nuclear Medicine (ABSNM), and the Commission for the Accreditation of Medical Physics Educational Programs (CAMPEP). The Task Force first met at the AAPM Annual Meeting in Charlotte in July 2012 and has met regularly face‐to‐face, online, and by conference calls. This manuscript reports the findings of the Task Force, as well as recommendations to achieve the stated mission.PACS number: 01.40.G‐