bluuebunny/crossref_metadata_2025 huggingface dataset:
Adhesion Molecule CD146 and its Soluble Form Correlate Well with Carotid Atherosclerosis and Plaque Instability
Authors: Qian Yi‐Ning , Luo Yong‐Ting , Duan Hong‐Xia , Feng Li‐Qun , Bi Qi , Wang Yong‐Jun , Yan Xi‐Yun
Published: February 2014

Aims

Intraplaque neovascularization and foam cell infiltration contribute to the development of unstable plaque, leading to thromboembolism and stroke. Cell adhesion molecules (CAMs) have been reported to be involved in the progression of atherosclerosis and plaque vulnerability. The aim of this study was to assess the association of adhesion molecule CD146 with carotid plaque instability.

Methods

We collected forty atherosclerotic plaques from 40 patients undergoing carotid endarterectomy. The clinical information of each patient was obtained, and the plaque morphology and characteristics were examined by the ultrasound. The CD146 expressions of the plaques were graded by using semiquantitative scales. The serum level of soluble form of CD146 was detected by enzyme‐linked immunosorbent assay (ELISA).

Results

CD146 expression was mainly on the intraplaque blood vessels and infiltrated macrophages. The CD146 expression was strongly correlated with the matrix metalloproteinase‐9(MMP‐9)expressions (P < 0.001) in the plaques. Soluble CD146 (sCD146) was also elevated in patients with atherosclerotic plaques. There was significant correlation between the increased CD146 expression and sCD146 level (P = 0.0057). sCD146 correlated well with serum MMP‐9 (P < 0.0044), IL‐6 (P = 0.0044) and high sensitivity C‐reactive protein (hsCRP) (P = 0.005).

Conclusions

Adhesion molecules CD146 and its soluble form strongly correlated with the development of inflammation of atherosclerosis and plaque instability. CD146 may be a promising biomarker for monitoring the development and instability of atherosclerotic plaque in patients with carotid diseases.
Standardized technique for single port laparoscopic ileostomy and colostomy
Authors: Shah A. , Moftah M. , Hadi Nahar Al‐Furaji H. , Cahill R. A.
Published: February 2014

Aim

Single site laparoscopic techniques and technology exploit maximum usefulness from confined incisions. The formation of an ileostomy or colostomy seems very applicable for this modality as the stoma occupies the solitary incision obviating any additional wounds.

Method

Here we detail the principles of our approach to defunctioning loop stoma formation using single port laparoscopic access in a stepwise and standardized fashion along with the salient specifics of five illustrative patients. No specialized instrumentation is required and the single access platform is established table‐side using the ‘glove port’ technique.

Results

The approach has the intra‐operative advantage of excellent visualization of the correct intestinal segment for exteriorization along with direct visual control of its extraction to avoid twisting. Postoperatively, abdominal wall trauma has been minimal allowing convalescence and stoma care education with only one parietal incision.

Conclusion

Single incision stoma siting proves a ready, robust and reliable technique for diversion ileostomy and colostomy with a minimum of operative trauma for the patient.
Re‐Evaluation of Yellowstone Grizzly Bear Population Dynamics not Supported by Empirical Data: Response to Doak & Cutler
Authors: van Manen Frank T. , Ebinger Michael R. , Haroldson Mark A. , Harris Richard B. , Higgs Megan D. , Cherry Steve , White Gary C. , Schwartz Charles C.
Published: February 2014

Doak and Cutler critiqued methods used by the Interagency Grizzly Bear Study Team (IGBST) to estimate grizzly bear population size and trend in the Greater Yellowstone Ecosystem. Here, we focus on the premise, implementation, and interpretation of simulations they used to support their arguments. They argued that population increases documented by IGBST based on females with cubs‐of‐the‐year were an artifact of increased search effort. However, we demonstrate their simulations were neither reflective of the true observation process nor did their results provide statistical support for their conclusion. They further argued that survival and reproductive senescence should be incorporated into population projections, but we demonstrate their choice of extreme mortality risk beyond age 20 and incompatible baseline fecundity led to erroneous conclusions. The conclusions of Doak and Cutler are unsubstantiated when placed within the context of a thorough understanding of the data, study system, and previous research findings and publications.
Rope dyeing of fabric in supercritical carbon dioxide for commerical purposes
Authors: Yang Mu‐Ying , Liu Jing , Zhang Yan‐Qin , Chen Chen , Wang Ke , Peng Cheng , Long Jia‐Jie
Published: February 2014

A novel method for fabric rope dyeing in supercritical carbon dioxide fluid has been successfully developed for the first time for commercial purposes by employing a custom‐built machine. The influence of parameters such as system pressure, temperature, and dyeing time on fabric colour strength was investigated, and the parameters optimised. Moreover, the level dyeing property, reproducibility, and colour fastness were investigated and evaluated under various conditions. The carbon dioxide recycling efficiency and the running costs of the proposed process in comparison with conventional processes for commercial production purposes were also investigated. The rope dyeing results show significant influence of the process parameters on fabric colour strength. Satisfactory and commercially acceptable products with a good level dyeing property, high reproducibility of coloration, and good fastness, rated at 4–5 or 5 for washing and rubbing, were obtained with supercritical carbon dioxide fluid. Moreover, a carbon dioxide recycling efficiency ranging from 92 to 95.2% was possible. In comparison with conventional dyeing processes, running costs were lowered by employing the proposed process and rope dyeing machine.
Preparation and application of ultrahigh‐pressure‐homogenised aminosilicon‐based softeners
Authors: Kwon Soon Chul , Lee Kwon Sun , Shim Jae Yun , Jeong Sung Hoon , Koh Joonseok , Kim Sung Dong
Published: February 2014

Five different aminosilicon‐based softeners were prepared by ultrahigh‐pressure homogenisation, and changes in their particle sizes and spectroscopic properties were investigated. Moreover, the yellowing characteristics and mechanical properties of cotton fabrics treated with the homogenised softeners were determined. Homogenisation significantly decreased the average particle sizes and particle size distribution without destroying the micelles. In particular, from the results on changes in the whiteness and yellowness of a cotton fabric treated with a silicon‐based softener, it was confirmed that homogenisation suppresses the yellowing of the fabrics.
Predictors of reduced tacrolimus dose and trough level through 36 months post‐transplant among 578 adult primary kidney transplant recipients
Authors: Gaynor Jeffrey J. , Ciancio Gaetano , Guerra Giselle , Sageshima Junichiro , Roth David , Chen Linda , Kupin Warren , Mattiazzi Adela , Tueros Lissett , Flores Sandra , Hanson Lois , Vianna Rodrigo , Burke George W.
Published: February 2014

Background

A multivariable linear regression model including baseline and immunosuppression‐related predictors of the post‐kidney transplant tacrolimus dose/day required for achieving a target tacrolimus trough level of 4–8 ng/mL (currently accepted reduced tacrolimus dosing strategy) would provide a practical guide to clinicians.

Methods

Using our prospectively followed cohort of 578 adult primary kidney transplant recipients assigned to receive reduced tacrolimus dosing as part of maintenance therapy, we determined the significant predictors of absolute tacrolimus dose (mg), tacrolimus trough level (ng/mL), and dose‐adjusted tacrolimus trough level (%/L) during the first 36 months post‐transplant.

Results

Two demographic variables were associated with a significantly higher tacrolimus dose at each post‐transplant time analyzed: African American recipient (p < 0.000001) and younger recipient age (p ≤ 0.00009). Use of maintenance corticosteroids was also associated with a significantly higher tacrolimus dose but only during the first 12 months post‐transplant (p ≤ 0.002). None of the other baseline variables (or use of sirolimus) were predictive of tacrolimus dose, and none of these factors were associated with the tacrolimus trough level (thus, effective therapeutic drug monitoring was achieved). Results for dose‐adjusted tacrolimus trough level were inversely related to the tacrolimus dose findings.

Conclusions

Significantly higher tacrolimus dosing to achieve the target tacrolimus trough level (lower bioavailability) was required, but only among African Americans, younger recipients, and those receiving maintenance corticosteroids.
Parathyroid hormone and clinical outcome in kidney transplant patients with optimal transplant function
Authors: Bleskestad Inger H. , Bergrem Harald , Leivestad Torbjørn , Hartmann Anders , Gøransson Lasse G.
Published: February 2014

Background

The aim of the study was to investigate whether serum levels of intact parathyroid hormone (iPTH) are associated with an increased risk of cardiovascular events, graft loss, or mortality in kidney transplant patients with optimal transplant function.

Methods

From the Norwegian Renal Registry, we identified 522 patients who received a first kidney transplant from 2001 to 2008 with optimal transplant function defined as an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, more than one yr after transplantation. Cox's proportional hazard models were used to assess the association between iPTH measured 10 wk after transplantation and the composite endpoint. The estimates were adjusted for age, gender, serum calcium, serum phosphate, diabetes mellitus, cardiovascular disease, and time on dialysis prior to transplantation.

Results

Median follow‐up time was 3.9 yr (interquartile range, IQR: 2.0–6.0 yr). Patients in the third iPTH quartile (9.3–14.4 pM) had the lowest risk for reaching the composite endpoint. Patients in the fourth iPTH quartile (>14.4 pM) had an increased risk compared to those in the third quartile (HR: 2.60, 95% CI: 1.10–6.16, p = 0.03).

Conclusion

In patients with optimal transplant function, iPTH levels are associated with a clinical outcome consisting of cardiovascular events, graft loss, and all‐cause mortality.
Lymph node fine needle aspiration cytology in systemic mastocytosis: cytological features with ancillary tests and literature review
Authors: Cozzolino I. , Picardi M. , Lucci R. , Petraroli A. , Spadaro G. , Marone G. , Vetrani A. , Zeppa P.
Published: February 2014

Objective

Systemic mastocytosis (SM) may rarely involve the lymph nodes; the corresponding cytological features are variable and have rarely been described. The aim of this study was to define more clearly the corresponding cytological diagnostic criteria.

Methods

Ultrasound‐guided fine needle aspiration (FNA) of the deep‐seated lymph nodes of two men, aged 72 and 75 years respectively, was performed with rapid on‐site evaluation (ROSE). Additional passes were used to prepare alcohol‐fixed smears for immunocytochemistry (ICC) and cell suspensions for flow cytometry (FC).

Results

Smears showed medium‐sized, roundish or elongated, mast cells with round to oval nuclei, sometimes irregular in shape. Cytoplasm was abundant with coarse granules, magenta‐stained on Diff‐Quik® smears. Mature lymphocytes, plasma cells, histiocytes and a variable number of eosinophils were present in the background. ICC showed mast cell positivity for CD117 in both cases; FC demonstrated CD2/CD25 co‐expression in one case. On the basis of the cytological and phenotypical features, the diagnosis of lymph node involvement in SM was made in both cases. Cytological ICC and FC data were evaluated using information reported in the literature.

Conclusions

Lymph node involvement in SM may be detected by FNA and ancillary techniques successfully applied to demonstrate the mast cell phenotype. FNA may also be used in a multidisciplinary algorithm for timely and effective SM staging.
Additive effects of social and non‐social attention during infancy relate to later autism spectrum disorder
Authors: Bedford Rachael , Pickles Andrew , Gliga Teodora , Elsabbagh Mayada , Charman Tony , Johnson Mark H. ,   the BASIS Team
Published: February 2014

Emerging findings from studies with infants at familial high risk for autism spectrum disorder (ASD), owing to an older sibling with a diagnosis, suggest that those who go on to develop ASD show early impairments in the processing of stimuli with both social and non‐social content. Although ASD is defined by social‐communication impairments and restricted and repetitive behaviours, the majority of cognitive theories of ASD posit a single underlying factor, which over development has secondary effects across domains. This is the first high‐risk study to statistically differentiate theoretical models of the development of ASD in high‐risk siblings using multiple risk factors. We examined the prediction of ASD outcome by attention to social and non‐social stimuli: gaze following and attentional disengagement assessed at 13 months in low‐risk controls and high‐risk ASD infants (who were subsequently diagnosed with ASD at 3 years). When included in the same regression model, these 13‐month measures independently predicted ASD outcome at 3 years of age. The data were best described by an additive model, suggesting that non‐social attention, disengagement, and social attention as evidenced by gaze following, have a cumulative impact on ASD risk. These data argue against cognitive theories of ASD which propose that a single underlying factor has cascading effects across early development leading to an ASD outcome, and support multiple impairment models of ASD that are more consistent with recent genetic and neurobiological evidence.
Using trait and phylogenetic diversity to evaluate the generality of the stress‐dominance hypothesis in eastern North American tree communities
Authors: Coyle Jessica R. , Halliday Fletcher W. , Lopez Bianca E. , Palmquist Kyle A. , Wilfahrt Peter A. , Hurlbert Allen H.
Published: February 2014

The stress‐dominance hypothesis (SDH) is a model of community assembly predicting that the relative importance of environmental filtering increases and competition decreases along a gradient of increasing environmental stress. Tests of the SDH at limited spatial scales have thus far demonstrated equivocal support and no prior study has assessed the generality of the SDH at continental scales. We examined over 53 000 tree communities spanning the eastern United States to determine whether functional trait variation and phylogenetic diversity support the SDH for gradients of water and soil nutrient availability. This analysis incorporated two complementary datasets, those of the U.S. Forest Service Forest Inventory and Analysis National program and the Carolina Vegetation Survey, and was based on three ecologically important traits: leaf nitrogen, seed mass, and wood density. We found that mean trait values were weakly correlated with water and soil nutrient availability, but that trait diversity did not vary consistently along either gradient. This did not conform to trait variation expected under the SDH and instead suggested that environmental filters structure tree communities throughout both gradients, without evidence for an increased role of competition in less stressful environments. Phylogenetic diversity of communities was principally driven by the ratio of angiosperms to gymnosperms and therefore did not exhibit the pattern of variation along stress gradients expected under the SDH. We conclude that the SDH is not a general paradigm for all eastern North American tree communities, although it may operate in certain contexts.
Inferring maximum lifespan from maximum recorded longevity in the wild carries substantial risk of estimation bias
Authors: Baylis Shane M. , de Lisle Mark , Hauber Mark E.
Published: February 2014

When comparing lifespan (longevity) between species, it is common practice to take the maximum recorded longevity value within each species as a proxy of maximum lifespan. Whether maximum recorded longevity is a reliable proxy of species' maximum longevity remains unclear. Some researchers correct for previously documented life history correlates of maximum recorded longevity before analysing new predictors of lifespan across species in the context of their current, specific hypotheses. At present there is no certainty that all relevant statistical, phenotypic, or ecological biases are accounted for by such corrective measures. Here, we employ Monte Carlo simulation to investigate the effect of differences in recapture numbers, recapture types (the point in life at which individuals are initially captured or recaptured), and actuarial population decay structure of simulated species on their maximum recorded longevities. We show that maximum recorded longevities differ in response to all three of these variables, as well as all of their two‐ and three‐way interactions. We then investigate empirical avian band‐recapture data for evidence of biases caused by recapture number and recapture type, predicted by the Monte Carlo analysis, and confirm the predicted biases as major sources of variance. Finally, we investigate the relationship between recapture type, recapture number, and a selection of ecological and life‐history variables previously documented to correlate with maximum recorded longevity, and find significant correlations between the biasing variables and those published correlates. Our results call into question the validity of using maximum recorded longevity as a proxy for different species' maximum longevities in comparative studies investigating the evolution of lifespan.
Inequality, Community Participation, and the Allocation of Collective Profits
Authors: Alix‐Garcia Jennifer , Harris Benjamin Cerf
Published: February 2014

This study analyzes the relationship between inequality in land holdings and participation in community assemblies in Mexican villages. Our identification strategy is unique in that it exploits contemporaneously exogenous variation in inequality due to historic and legal restrictions on the subdivision and sale of parcels in the communities we study. The data show that at an aggregate level, villages with more inequality in land holdings have lower participation rates. Individuals with greater land holdings relative to other community members are more likely to participate. This relationship intensifies with increasing inequality. We also consider how participation influences the allocation of public funds. We find greater investment in public goods where inequality is lower and participation higher. Finally, we demonstrate that those who are less likely to attend meetings are also less likely to receive government subsidies and benefits.
The Human and Educational Significance of Honesty as an Epistemic and Moral Virtue
Authors: Carr David
Published: February 2014

While honesty is clearly a virtue of some educational as well as moral significance, its virtue‐ethical status is far from clear. In this essay, following some discussion of latter‐day virtue ethics and virtue epistemology, David Carr argues that honesty exhibits key features of both moral and epistemic virtue, and, more precisely, that honesty as a virtue might best be understood as the epistemic component of Aristotelian practical wisdom. In the wake of arguments to be found in Plato's Laws, as well as in those of more modern philosophers such as Jean‐Jacques Rousseau and Iris Murdoch, Carr then traces the main roots of moral dishonesty to various forms of vain and self‐delusive ego attachment. In this light, he argues in the final section of the essay that literature and the arts may provide a powerful educational antidote to such attachment.
The Dialectical Relationship Between Place and Space in Education: How the Internet Is Changing Our Perceptions of Teaching and Learning
Authors: Glassman Michael , Burbidge Jonathan
Published: February 2014

In this essay Michael Glassman and Jonathan Burbidge explore the idea of a dialectical relationship between the traditional place(s) of teaching/learning settings and the challenges to our perceptions created by the new spaces of the Internet. The authors examine this topic in the context of a three‐stage evolution of humans' relationship with new technologies: (1) fear of how new technologies will change our everyday actions, (2) recognition of emerging technologies as tools capable of offering new possibilities in our activities, and (3) integration of new technologies into productive everyday activities. The Internet is moving quickly through all three stages, but this process takes different forms with disparate populations. What makes recognition of the fast‐moving integration of Internet technology important in the field of education is that students and educators are often at different points in this process. It is critical that we are aware of the role technology is playing in the classroom, in particular the dynamic dialectical relationship between space and place.
The Difference Differentiation Makes: Extending Eisner's Account
Authors: Blanken‐Webb Jane
Published: February 2014

In this analysis Jane Blanken‐Webb extends Elliot Eisner's account of how learning in the arts contributes to the creation of mind. Drawing on the psychoanalytic theory of D. W. Winnicott, Blanken‐Webb argues that the acts of meaning making to which Eisner attends rely on a prior developmental achievement — namely, the establishment of self‐in‐relation‐to‐world. This prior development is important to recognize in order to appreciate all that is at stake and at play within acts of meaning making. To demonstrate this, Blanken‐Webb points to reverberations of an earlier process of psychological differentiation embedded within such acts that are crucial for aesthetic experience and that carry on a continual process of refinement of self‐in‐relation‐to‐world. While Eisner has a great deal to offer regarding the importance of providing students access to multiple forms of representation, this perspective adds that in doing so we are expanding on a foundation of self‐in‐relation‐to‐world, thus facilitating an educational unfolding that is much deeper than we typically recognize.
Predictors of vocational activity over the first year in inner‐city early intervention in psychosis services
Authors: Tapfumaneyi Andrew , Johnson Sonia , Joyce John , Major Barnaby , Lawrence Jo , Mann Farhana , Chisholm Brock , Rahaman Nikola , Wooley James , Fisher Helen L. ,   MiData Consortium
Published: February 2014

Aim

Work and educational activities are an important part of recovery for young people with psychosis, and improving vocational outcomes is a key target for early intervention services (EIS). This study evaluated predictors of vocational activity for first‐episode psychosis (FEP) patients during the first year of EIS care. It was hypothesized that longer duration of untreated psychosis (DUP) and minority ethnic status would predict poorer vocational outcomes, whereas a history of good vocational functioning would predict better vocational functioning during follow up.

Methods

FEP patients aged 14–35 years, who presented to seven EIS in London, UK, between 2003 and 2010, were followed for 1 year. Sociodemographic, clinical and vocational information (qualifications obtained and paid employment) were collected using the MiData audit tool at entry to EIS and 1 year later.

Results

Approximately one‐third of patients (n = 345/1013) were studying or employed at some point during the first year of EIS care. Baseline vocational activity was the strongest predictor of vocational functioning during 1 year of follow up. Moreover, employment prior to entry into EIS strongly predicted change in vocational activity during 1 year of follow up. Individuals with DUP <6 months or of Asian or black African origin were more likely to be studying than their white British counterparts.

Conclusion

This study confirms that a significant proportion of FEP patients are able to engage in meaningful vocational activities even within the first year of EIS care. However, services need to focus more resources on getting patients with poor educational or employment histories into training programmes to improve their vocational outcomes.
Monocyte/macrophage‐derived soluble CD163: a novel biomarker in multiple myeloma
Authors: Andersen Morten N. , Abildgaard Niels , Maniecki Maciej B. , Møller Holger J. , Andersen Niels F.
Published: February 2014

Objectives

Macrophages play an important role in cancer by suppression of adaptive immunity and promotion of angiogenesis and metastasis. Tumor‐associated macrophages strongly express the hemoglobin scavenger receptor CD163, which can also be found as a soluble protein in serum and other body fluids (soluble CD163, sCD163). In this study, we examined serum sCD163 as a biomarker in patients with newly diagnosed multiple myeloma.

Methods

Peripheral blood (n = 104) and bone marrow (n = 17) levels of sCD163 were measured using an enzyme‐linked immunosorbent assay.

Results

At diagnosis, high sCD163 was associated with higher stage according to the International Staging System (ISS) and with other known prognostic factors in multiple myeloma (creatinine, C‐reactive protein, and beta‐2 microglobulin). Soluble CD163 decreased upon high‐dose treatment, and in a multivariate survival analysis including the covariates treatment modality and age at diagnosis, higher levels of sCD163 were associated with poor outcome (HR = 1.82; P = 0.010). The prognostic significance of sCD163 was lost when including ISS stage in the model (HR = 1.51; P = 0.085). Soluble CD163 values were significantly higher in bone marrow samples than in the matched blood samples, which indicate a localized production of sCD163 within the bone marrow microenvironment.

Conclusions

Soluble CD163 was found to be a prognostic marker in patients with multiple myeloma. This may indicate that macrophages and/or monocytes have an important role in the bone marrow microenvironment of myeloma patients, supporting myeloma cell proliferation and survival. We propose the serum sCD163 value 1.8 mg/L as a cutoff concentration for survival analysis in patients with multiple myeloma, which should be validated in future studies.
Intracranial atherosclerotic disease
Authors: Battistella V. , Elkind M.
Published: February 2014

Atherosclerotic disease of the intracranial arteries is responsible for at least 10% of ischaemic strokes worldwide. Symptomatic disease has been extensively studied in the past few years, using diagnostic methods including multi‐slice computed tomography and high resolution magnetic resonance imaging. A literature search was performed using PubMed and OvidSP between 1984 and May 2013. Variations of the terms ‘intracranial atherosclerosis’ plus ‘ischemic stroke’, ‘plaque’, ‘morphology’, ‘imaging’ were used and a combination of them. The reference lists of identified articles were also consulted for additional references. Amongst symptomatic patients the prevalence of intracranial atherosclerotic disease is around 10%, depending on race ethnicity, and the diagnosis requires the presence of ≥50% stenosis in the territory of the symptomatic vessel in a patient with stroke or transient ischaemic attack. The prognosis of intracranial atherosclerotic disease related stroke is poor. Although risk factor control can lead to a better outcome of intracranial atherosclerotic disease related strokes, the significance of asymptomatic disease is still a matter of debate.
Comparison of stent retriever and intra‐arterial fibrinolysis in patients with acute ischaemic stroke
Authors: Song D. , Kim B. M. , Kim D. J. , Kim Y. D. , Kim J. , Lee H. S. , Nam H. S. , Heo J. H.
Published: February 2014

Background and purpose

Although the stent retriever (SR) has shown a better reperfusion rate and clinical outcome than the older generation mechanical clot retrieval device, it is uncertain whether the SR is superior to intra‐arterial fibrinolysis (IAF).

Methods

Ischaemic stroke patients who were treated with SR or IAF as initial endovascular treatment modality for unilateral arterial occlusion in the anterior circulation were included. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction grade ≥2b. A favourable clinical outcome was defined as a modified Rankin Score ≤2 at 3 months.

Results

Between January 2009 and May 2012, 55 patients were treated with SR and 50 patients were treated with IAF. The baseline characteristics were similar between the two groups except for the occlusion site and rescue treatment. In binary logistic regression analysis adjusted for the occlusion site and rescue treatment, SR was independently associated with increased successful reperfusion [82.0% vs. 47.3%; odds ratio (OR) 5.21; 95% confidence interval (CI) 1.92–14.14) and a more favourable clinical outcome at 3 months (54.0% vs. 43.6%; OR 3.40; 95% CI 1.31–8.84). The frequency of symptomatic intracranial haemorrhage and mortality at 3 months was not different between the two groups.

Conclusions

Stent retriever was as safe as and more effective than IAF. Our findings suggest that SR may be considered as an initial modality rather than IAF in acute stroke patients who undergo endovascular treatment.
Adjunctive zonisamide therapy in the long‐term treatment of children with partial epilepsy: Results of an open‐label extension study of a phase III, randomized, double‐blind, placebo‐controlled trial
Authors: Guerrini Renzo , Rosati Anna , Bradshaw Kate , Giorgi Luigi
Published: February 2014

Objective

To investigate the safety/tolerability and efficacy of long‐term adjunctive zonisamide and its impact on growth and development in children (6–18 years) with partial epilepsy.

Methods

Open‐label extension of a phase III, placebo‐controlled trial. Started with double‐blind transition period (2–11 weeks), during which patients on zonisamide continued at the same dose and those on placebo switched to zonisamide 1 mg/kg/day, up‐titrated to 8 mg/kg/day (maximum 500 mg/day). During the subsequent open‐label period (45–57 weeks), zonisamide dosing could be adjusted according to tolerability/response. Safety assessments included treatment‐emergent adverse events (TEAEs), clinical laboratory parameters, and vital signs. Efficacy assessments included responder rate (primary assessment) and seizure freedom rate during the open‐label period. Growth and development assessments comprised Tanner stages, hand x‐rays, Child Behavior Checklist (CBCL 6/18), School Performance questionnaire, Physician and Parent/Guardian Global Impression of Change, and Controlled Oral Word Association Test (COWAT).

Results

One hundred forty‐four children entered the study; 99 (68.8%) of 144 children completed it, and 108 (75.0%) of 144 received zonisamide for ≥1 year. TEAEs occurred in 39 (27.1%) of 144 patients. There were low incidences of serious TEAEs (2.1%) and TEAEs leading to discontinuation (2.8%). Bicarbonate level decreases >3.5 mm occurred in 64 patients (44.4%), and 24 patients (16.7%) had a weight decrease of ≥10% from baseline. During the open‐label period, 81 (56.3%) of 144 patients were responders and 16 (11.1%) of 144 achieved seizure freedom. Tanner staging and skeletal development were as expected for the study population. Changes were minimal for CBCL 6/18 and School Performance scores. Most patients were “much improved”/“very much improved” on Physician (73.8%) and Parent/Guardian (75.4%) Global Impressions of Change. Median changes in COWAT Category and Letter Fluency scores were 2.0 and 0.5, respectively.

Significance

Adjunctive zonisamide was well tolerated and efficacious over a period of at least 1 year in children with partial epilepsy, with no unexpected safety concerns and no consistent detrimental effects on growth and development.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Attention and executive functions in a rat model of chronic epilepsy
Authors: Faure Jean‐Baptiste , Marques‐Carneiro José E. , Akimana Gladys , Cosquer Brigitte , Ferrandon Arielle , Herbeaux Karine , Koning Estelle , Barbelivien Alexandra , Nehlig Astrid , Cassel Jean‐Christophe
Published: February 2014

Objective

Temporal lobe epilepsy is a relatively frequent, invalidating, and often refractory neurologic disorder. It is associated with cognitive impairments that affect memory and executive functions. In the rat lithium‐pilocarpine temporal lobe epilepsy model, memory impairment and anxiety disorder are classically reported. Here we evaluated sustained visual attention in this model of epilepsy, a function not frequently explored.

Methods

Thirty‐five Sprague‐Dawley rats were subjected to lithium‐pilocarpine status epilepticus. Twenty of them received a carisbamate treatment for 7 days, starting 1 h after status epilepticus onset. Twelve controls received lithium and saline. Five months later, attention was assessed in the five‐choice serial reaction time task, a task that tests visual attention and inhibitory control (impulsivity/compulsivity). Neuronal counting was performed in brain regions of interest to the functions studied (hippocampus, prefrontal cortex, nucleus basalis magnocellularis, and pedunculopontine tegmental nucleus).

Results

Lithium‐pilocarpine rats developed motor seizures. When they were able to learn the task, they exhibited attention impairment and a tendency toward impulsivity and compulsivity. These disturbances occurred in the absence of neuronal loss in structures classically related to attentional performance, although they seemed to better correlate with neuronal loss in hippocampus. Globally, rats that received carisbamate and developed motor seizures were as impaired as untreated rats, whereas those that did not develop overt motor seizures performed like controls, despite evidence for hippocampal damage.

Significance

This study shows that attention deficits reported by patients with temporal lobe epilepsy can be observed in the lithium‐pilocarpine model. Carisbamate prevents the occurrence of motor seizures, attention impairment, impulsivity, and compulsivity in a subpopulation of neuroprotected rats.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Simulating local adaptation to climate of forest trees with a Physio‐Demo‐Genetics model
Authors: Oddou‐Muratorio Sylvie , Davi Hendrik
Published: February 2014

One challenge of evolutionary ecology is to predict the rate and mechanisms of population adaptation to environmental variations. The variations in most life history traits are shaped both by individual genotypic and by environmental variation. Forest trees exhibit high levels of genetic diversity, large population sizes, and gene flow, and they also show a high level of plasticity for life history traits. We developed a new Physio‐Demo‐Genetics model (denoted PDG) coupling (i) a physiological module simulating individual tree responses to the environment; (ii) a demographic module simulating tree survival, reproduction, and pollen and seed dispersal; and (iii) a quantitative genetics module controlling the heritability of key life history traits. We used this model to investigate the plastic and genetic components of the variations in the timing of budburst (TBB) along an elevational gradient of Fagus sylvatica (the European beech). We used a repeated 5 years climatic sequence to show that five generations of natural selection were sufficient to develop nonmonotonic genetic differentiation in the TBB along the local climatic gradient but also that plastic variation among different elevations and years was higher than genetic variation. PDG complements theoretical models and provides testable predictions to understand the adaptive potential of tree populations.
Expression of p53, Ki67, EcPV2‐ and EcPV3 DNA, and viral genes in relation to metastasis and outcome in equine penile and preputial squamous cell carcinoma
Authors: van den Top J. G. B. , Harkema L. , Lange C. , Ensink J. M. , van de Lest C. H. A. , Barneveld A. , van Weeren P. R. , Gröne A. , Martens A.
Published: February 2014

Reasons for performing study

Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis.

Objectives

To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival.

Study design

Retrospective case–control study using archived material.

Methods

Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real‐time PCR was used for quantification of E2, E6 and L1 mRNA.

Results

Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3%; G1 26.1%; G2 26.3%; G3 63.3%).

Conclusions

In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.
Effects of age on the pharmacokinetics and selected pharmacodynamics of intravenously administered fentanyl in foals
Authors: Knych H. K. , Steffey E. P. , Mitchell M. M. , Casbeer H. C.
Published: February 2014

Reasons for performing study

The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration‐related behavioural actions of fentanyl have not been described for young foals.

Objectives

The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages.

Study design

Experimental study in healthy foals.

Methods

Fentanyl was administered i.v. (4 μg/kg bwt) to a group of 9 foals on 3 separate occasions at 6–8, 20–22 and 41–42 days of age. Blood samples were collected prior to administration and at multiple times until 24 h post administration. Blood samples were analysed for fentanyl concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed.

Results

The average volume of distribution was 3.55, 1.53 and 1.82 l/kg bwt and clearance 50.2, 40.7 and 35.7 ml/min/kg bwt when foals were 6–8, 20–22 and 41–42 days of age, respectively. The elimination half‐life was slightly prolonged (49.3 min) at 6–8 days relative to 20–22 and 41–42 days of age (25.8 and 33.7 min, respectively). The primary metabolite detected in blood samples was the same as for adult horses. While the onset and duration varied widely between foals, sedation was observed at all ages studied.

Conclusions

Fentanyl appears to be consistently well tolerated following i.v. administration of 4 μg/kg bwt to foals ranging in age from 1 to 6 weeks. The results of this study support further study of fentanyl for clinical use in foals.
Family matters: sibling rivalry and bonding between p53 and p63 in cancer
Authors: Romano Rose‐Anne , Sinha Satrajit
Published: February 2014

The p53 family (p53, p63 and p73) is intimately linked with an overwhelming number of cellular processes during normal physiological as well as pathological conditions including cancer. The fact that these proteins are expressed in myriad isoforms, each with unique biochemical properties and distinct effects on tumorigenesis, complicates their study. A case in point is Squamous Cell Carcinoma (SCC) where p53 is often mutated and the ΔNp63 isoform is overexpressed. Given that p53 and p63 can hetero‐dimerize, bind to quite similar DNA elements and share common co‐factors, any alterations in their individual expression levels, activity and/or mutation can severely disrupt the family equilibrium. The burgeoning genomics data sets and new additions to the experimental toolbox are offering crucial insights into the complex role of the p53 family in SCC, but more mechanistic studies are needed.
Analysis of 5‐lipoxygenase phosphorylation on molecular level by MALDI‐MS
Authors: Markoutsa Stavroula , Sürün Duran , Karas Michael , Hofmann Bettina , Steinhilber Dieter , Sorg Bernd L.
Published: February 2014

The enzyme 5‐lipoxygenase (5‐LO) catalyzes the first reactions in the biosynthesis of leukotrienes, powerful lipid mediators that are involved in several physiological and pathological processes. 5‐LO activity is tightly regulated by several factors, including post translational modifications (PTMs). Phosphorylations of 5‐LO by the kinases extracellular signal‐regulated kinase 2 (Erk2), mitogen‐activated protein kinase activated protein kinase 2 (MK2) and protein kinase A (PKA) have been described to regulate 5‐LO activity. Furthermore, 5‐LO phosphorylation is considered a determinant of drug candidate potency. However, no evidence on a molecular level, as can be provided by MS, has as yet been presented for these PTMs. Here, we employ a workflow including different proteolytic cleavages and phosphopeptide enrichment for detection of 5‐LO phosphorylation by MALDI‐MS. Proof for the known phosphorylation sites of MK2 (Ser271) and PKA (Ser523) was provided by MS after in vitro phosphorylation, but not for the postulated Erk2 site (Ser663). Detection limits have been determined for all three sites. Moreover, we identified novel tyrosine kinase target sites within 5‐LO using in silico and in vitro methods. Tyr42, Tyr53 and either Tyr94 or Tyr445 were phosphorylated by the Src kinases Fgr, hematopoietic cell kinase (HCK) and Yes. To analyze the phosphorylation state in the cellular context, we created stably 5‐LO‐transduced Mono Mac 6 cells. Here, we only detected phospho‐Ser271 by MS, whereas immunoblot analysis indicated tyrosine phosphorylation, phospho‐Ser271 and phospho‐Ser663. Unexpectedly, phospho‐Ser271 occurred independent of cell stimulation. Taken together, we describe a method for the molecular analysis of 5‐LO phosphorylation, provide insights regarding the occurrence of known phosphorylation sites partly in contrast to earlier studies and present first evidence on novel phosphosites.

Structured digital abstract

Yes phosphorylates 5-LO by enzymatic study (1, 2)

PKA phosphorylates 5-LO by enzymatic study (1, 2)

CaMK II phosphorylates 5-LO by enzymatic study (View interaction)

Fgr phosphorylates 5-LO by enzymatic study (1, 2)

MK2 phosphorylates 5-LO by enzymatic study (View interaction)

HCK phosphorylates 5-LO by enzymatic study (1, 2)
Finite element estimation of the plastic ηpl factors for pipe‐ring notched bend specimen using the load separation method
Authors: Likeb A. , Gubeljak N. , Matvienko Y. G.
Published: February 2014

The object of this paper is to develop the load separation method for the new pipe‐ring notched bend specimen. The paper presents an approach for determining the plastic load line displacement (ηplLLD) and the plastic crack mouth opening displacement (ηplCMOD) correction factors for pipe‐ring notched bend specimens. The estimated plastic factors are possible to use in estimation approach based on load versus displacement test. The ηpl factors could be applied for fracture toughness testing of pipeline materials when standard specimens cannot be applied. Finite element method is employed for estimating the separation parameters. The notch tip radius of blunt notched specimens varies within an interval Rn = 0, 0.1, 0.25, 0.5, 0.75, 1.25, 1.5 and 2 mm. The effect of the notch tip radius on the ηpl factors is analyzed.
Scaled body‐mass index shows how habitat quality influences the condition of four fish taxa in north‐eastern Spain and provides a novel indicator of ecosystem health
Authors: Maceda‐Veiga Alberto , Green Andy J. , De Sostoa Adolfo
Published: February 2014

Natural and anthropogenic disturbances are key forces governing the structure and functioning of aquatic communities. Understanding how these factors shape organism performance can help to identify the most vulnerable species and develop effective management strategies. This is particularly important for ichthyofaunas with high endemicity and low diversity, such as those of the Iberian Peninsula.

We explored the suitability of a novel and simple condition index, the scaled mass index (SMI), based on mass–length relationships, for analysis of the effects that abiotic and biotic pressures have on the body condition of four fish taxa widely distributed in Mediterranean rivers in north‐eastern Spain: brown trout (Salmo trutta), Iberian redfin barbel (Barbus haasi), Ebro barbel (Luciobarbus graellsii) and minnows (Phoxinus spp.). The SMI performed better in explaining spatial variation in body condition than the Fulton Index, a traditional method for fish studies.

For all taxa, anthropogenic stressors influencing water quality and physical habitat explained more variance in SMI than other factors. Variation partitioning and GLM approaches consistently showed that SMI increased with altitude, reduced concentrations of toxic nitrogenous compounds, and well‐preserved riparian canopy and natural channel morphology, despite the fact that three of the study taxa are in expansion and generally considered ‘tolerant’. In addition, the application of SMI to an independent fish data set showed that SMI provides a novel indicator of ecosystem health, which performs better than the current index of biotic integrity developed in this region.

We discuss the likely mechanisms behind the strong effects of habitat quality on SMI and the implications for our understanding of tolerance. Incorporating SMI into studies of fish monitoring is likely to improve the value of fish studies as indicators of river quality and ecological change. Further studies should compare the response of SMI to specific fish health indicators such as parasite load, haematological assays and pollutant bioaccumulation to improve our understanding of the value of SMI as a non‐lethal diagnostic procedure.