bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative contribution of spring- and summer-spawned bluefish cohorts to the adult population: effects of size-selective winter mortality, overwinter growth, and sampling bias
Authors: Morley James W. , Buckel Jeffrey A. , Lankford Thomas E.
Published: December 2012

Length distributions of juvenile bluefish (Pomatomus saltatrix) are bimodal, consisting of spring- and summer-spawned fish. Research during the 1990s from the northeastern United States suggested that the summer cohort contributes little to the adult population and that overwinter mortality may limit their survival. We examined length distributions of juvenile bluefish from before and after winter and found that the mean length of the summer cohort increased during winter. Based on a winter-growth experiment and temperatures from the two winters examined, changes in mean length were due to size-selective mortality for one year class and growth for the other. Despite evidence for winter mortality, summer-spawned bluefish were commonly caught at age 1. We reexamined the relative contribution of each cohort to the adult population using archived scales from North Carolina fisheries. Cohort origin of adults was determined by back-calculating length at age 1. One-third of adults consisted of summer-spawned fish, contrasting with previous research from the northeast. The differences in relative cohort abundance between the northeastern and southeastern United States arise from sized-based migration in age-1 and age-2 bluefish (the dominant age groups sampled in these studies) and the size-selective gear and sampling season in which they were collected.
Update on Thiol Status and Supplements in Physical Exercise
Authors: Sen Chandan K.
Published: December 2012

Strenuous physical exercise represents a condition that is often associated with increased production of reactive oxygen species in various tissues. One of the most reliable indices of exercise-induced oxidant production is tissue glutathione oxidation. In humans, exerciseinduced blood glutathione oxidation is rapid and subject to control by antioxidant supplementation. The objective of this brief review is to provide an update of our current understanding of cellular thiols and thiol antioxidants. Cellular thiols are critically important in maintaining the cellular antioxidant defense network. In addition, thiols play a key role in regulating redox-sensitive signal transduction process. Lipoic acid is a highly promising thiol antioxidant supplement. Recent studies have clarified that while higher levels of oxidants may indeed inflict oxidative damage, oxidants are not necessarily deleterious. Under certain conditions oxidants may function as cellular messengers that regulate a multitude of signal transduction pathways. In light of this, the significance of oxidants in various aspects of biology needs to be revisited.
Pre-exercise Nutritional Strategies: Effects on Metabolism and Performance
Authors: Hargreaves Mark
Published: December 2012

The goals of pre-exercise nutritional strategies are to optimise the availability of carbohydrate (CHO) and fluid. Ingestion of CHO 3-4 hr prior to exercise can increase liver and muscle glycogen stores and has been associated with enhanced endurance exercise performance. The metabolic effects of CHO ingestion persist for at least 6 hr. Although an increase in plasma insulin following CHO ingestion in the hour prior to exercise inhibits lipolysis and liver glucose output, and can lead to transient hypoglycemia during subsequent exercise, there is no convincing evidence that this is always associated with impaired exercise performance. Having said that, individual experience should inform individual practice. Interventions to increase plasma FFA availability prior to exercise have been shown to reduce CHO utilisation during exercise, but do not appear to have major ergogenic benefits. It is more difficult to hyperhydrate prior to exercise and although there has been interest in glycerol ingestion, to date research results have been equivocal. At the very least, athletes should ensure euhydration prior to exercise.
Creatine Supplementation: Exploring the Role of the Creatine Kinase/Phosphocreatine System in Human Muscle
Authors: Hespel Peter , Op ‘t Eijnde Bert , Derave Wim , Richter Erik A.
Published: December 2012

The effect of oral creatine supplementation on high-intensity exercise performance has been extensively studied over the past ten years and its ergogenic potential in young healthy subjects is now well documented. Recently, research has shifted from performance evaluation towards elucidating the mechanisms underlying enhanced muscle functional capacity after creatine supplementation. In this review, we attempt to summarise recent advances in the understanding of potential mechanisms of action of creatine supplementation at the level of skeletal muscle cells. By increasing intracellular creatine content, oral creatine ingestion conceivably stimulates operation of the creatine kinase (CK)/phosphocreatine (PCr) system, which in turn facilitates muscle relaxation. Furthermore, evidence is accumulating to suggest that creatine supplementation can beneficially impact on muscle protein and glycogen synthesis. Thus, muscle hypertrophy and glycogen supercompensation a1'e candidate factors to explain the ergogenic potential of creatine ingestion. Additional issues discussed in this review are the fibre-type specificity of muscle creatine metabolism, the identification of responders versus non-responders to creatine intake, and the scientific background concerning potential side effects of creatine supplementation.
Physical Health of the Female Athlete: Observations, Effects, and Causes of Reproductive Disorders
Authors: Loucks Anne B.
Published: December 2012

This review begins by summarizing the state of knowledge about menstrual disorders in athletes at the turn of the 21st Century. It then highlights the most important developments of outstanding interest that have been reported in the 18 months since then. New observations of the characteristics of these disorders are followed by new reports of clinical consequences and recommendations for treatment, and discoveries about their physiological mechanism. In general, evidence is continuing to accumulate that exercise has no suppressive effect on the reproductive system beyond the impact of its energy cost on energy availability. These results encourage the hope that athletic women may be able to prevent or reverse menstrual disorders by dietary supplementation without any moderation of their exercise regimen.
The Adverse Effects of Elite Competition on Health and Well-Being
Authors: Pipe Andrew
Published: December 2012

It is often assumed that participation in sport will produce only an array of health benefits. The adverse consequences of sport participation, particularly at the elite level, are rarely explored. Evidence continues to accumulate of a variety of unfortunate consequences that may accompany elite sport participation. Sport involvement may exacerbate pre-existing health problems, cause injury or even death. The sport environment may be hazardous in a variety of physical, emotional, and social ways. The common training and competition practices of certain sport cultures may themselves be hannful. Athletes may sacrifice health, home, education and nonnal social development in the pursuit of sport "success." Sport medicine professionals and sport scientists have particular opportunities and responsibilities to act as an athlete ‘s advocate—and to protect their health and well being.
Restoration of Fluid and Electrolyte Balance After Exercise
Authors: Shirreffs Susan M.
Published: December 2012

Post-exercise restoration of fluid balance after sweat-induced hypohydration avoids the detrimental effects of a body water deficit on physiological function and subsequent exercise peiformance. For effective restoration of fluid balance, the consumption of a volume of fluid in excess of the sweat loss and replacement of electrolyte, particularly sodium, losses are essential. Intravenous fluid replacement after exercise has been investigated to a lesser extent and its role for fluid replacement in the dehydrated but otherwise well athlete remains equivocal.
PROBABILISTIC HARMONIC ANALYSIS OF WIND GENERATORS BASED ON GENERALIZED GAMMA MIXTURE MODELS
Authors: XIE GUANGLONG , ZHANG BUHAN
Published: December 2012

Grid-connected wind generators pose the power quality problems such as harmonic propagation and summation, and these problems are hard to solve by deterministic harmonic analysis due to the random harmonic current emissions. In this paper, probabilistic harmonic analysis is utilized to approximate harmonic currents of wind generators. Generalized gamma mixture models based on Gaussian mixture models, phasor clustering and generalized gamma models, are proposed to approximate the probability density functions of harmonic propagation and summation. And the simulation network built on PSCAD/EMTDC is utilized to verify the proposed models and method.
EVOLUTION OF SHANGHAI STOCK MARKET BASED ON MAXIMAL SPANNING TREES
Authors: YANG CHUNXIA , SHEN YING , XIA BINGYING
Published: December 2012

In this paper, using a moving window to scan through every stock price time series over a period from 2 January 2001 to 11 March 2011 and mutual information to measure the statistical interdependence between stock prices, we construct a corresponding weighted network for 501 Shanghai stocks in every given window. Next, we extract its maximal spanning tree and understand the structure variation of Shanghai stock market by analyzing the average path length, the influence of the center node and the p-value for every maximal spanning tree. A further analysis of the structure properties of maximal spanning trees over different periods of Shanghai stock market is carried out. All the obtained results indicate that the periods around 8 August 2005, 17 October 2007 and 25 December 2008 are turning points of Shanghai stock market, at turning points, the topology structure of the maximal spanning tree changes obviously: the degree of separation between nodes increases; the structure becomes looser; the influence of the center node gets smaller, and the degree distribution of the maximal spanning tree is no longer a power-law distribution. Lastly, we give an analysis of the variations of the single-step and multi-step survival ratios for all maximal spanning trees and find that two stocks are closely bonded and hard to be broken in a short term, on the contrary, no pair of stocks remains closely bonded for a long time.
ORIGIN OF THE STRONGER ROBUSTNESS AGAINST CASCADING FAILURES OF COMPLEX NETWORKS: A MITIGATION STRATEGY PERSPECTIVE
Authors: WANG JIANWEI
Published: December 2012

Cascading failures can occur in many infrastructure networks. How to protect these networks and improve their robustness against cascading failures has been of great interest. To this end, considering that there exist some monitoring and protection measures in these networks, we propose a new mitigation strategy and investigate its effectiveness on improving the robustness level against cascading failures in Barabáasi-Albert (BA) networks and the power grid. We numerically observe that only by once adopting this strategy the robustness of BA networks and the power grid can be improved dramatically. We additionally find that BA networks and the power grid can reach the strongest robustness against cascading failures in the case of the specific value of the parameter α, which controls the strength of the initial load on a node. And we obtain the correlation between the load distribution and the effectiveness of the mitigation strategy. Our findings can well explain the origin of the stronger robustness against cascading failures of complex networks and may be very useful for guiding the improvement robustness of infrastructure networks and avoiding various cascading-failure-induced disasters in the real world.
HYDRODYNAMIC SCALING ANALYSIS OF NUCLEAR FUSION DRIVEN BY ULTRA-INTENSE LASER-PLASMA INTERACTIONS
Authors: KIMURA SACHIE , BONASERA ALDO
Published: December 2012

We discuss scaling laws of fusion yields generated by laser-plasma interactions. The yields are found to scale as a function of the laser power. The origin of the scaling law in the laser driven fusion yield is derived in terms of hydrodynamic scaling. We point out that the scaling properties can be attributed to the laser power dependence of three terms: the reaction rate, the density of the plasma and the projected range of the plasma particle in the target medium. The resulting scaling relations have a predictive power that enables estimating the fusion yield for a nuclear reaction which has not been investigated by means of the laser accelerated ion beams.
DIELECTRIC, FERROELECTRIC, PIEZOELECTRIC AND IMPEDANCE STUDY OF LEAD-FREE CERAMIC: SrBi4Ti3.975Zr0.025O15
Authors: MAMATHA B. , SARAH P.
Published: December 2012

Polycrystalline SrBi4Ti3.975Zr0.025O15 (SBTZ) was prepared using solid-state reaction technique. SBTZ was characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). XRD analysis indicated the formation of a single-phase orthorhombic structure. Particle size was found using SEM. The dielectric, ferroelectric, piezoelectric, modulus and impedance spectroscopy studies on SBTZ were investigated in the frequency range 1 Hz–1 MHz from room temperature (RT) to 600°C. Piezoelectric charge and electromechanical coupling coefficients were calculated from resonance and anti-resonance frequencies. Impedance and modulus plots were used as tools to analyze the sample behavior as a function of frequency. Cole–Cole plots showed a non-Debye relaxation. Conductivity measurements were performed on SBTZ.
Endoplasmic reticulum stress signal impairs erythropoietin production: a role for ATF4
Authors: Chiang Chih-Kang , Nangaku Masaomi , Tanaka Tetsuhiro , Iwawaki Takao , Inagi Reiko
Published: December 2012

Hypoxia upregulates the hypoxia-inducible factor (HIF) pathway and the endoplasmic reticulum (ER) stress signal, unfolded protein response (UPR). The cross talk of both signals affects the pathogenic alteration by hypoxia. Here we showed that ER stress induced by tunicamycin or thapsigargin suppressed inducible (CoCl2 or hypoxia) transcription of erythropoietin (EPO), a representative HIF target gene, in HepG2. This suppression was inversely correlated with UPR activation, as estimated by expression of the UPR regulator glucose-regulated protein 78, and restored by an ER stress inhibitor, salubrinal, in association with normalization of the UPR state. Importantly, the decreased EPO expression was also observed in HepG2 overexpressing UPR activating transcription factor (ATF)4. Overexpression of mutated ATF4 that lacks the transcriptional activity did not alter EPO transcriptional regulation. Transcriptional activity of the EPO 3′-enhancer, which is mainly regulated by HIF, was abolished by both ER stressors and ATF4 overexpression, while nuclear HIF accumulation or expression of other HIF target genes was not suppressed by ER stress. Chromatin immunoprecipitation analysis identified a novel ATF4 binding site (TGACCTCT) within the EPO 3′-enhancer region, suggesting a distinct role for ATF4 in UPR-dependent suppression of the enhancer. Induction of ER stress in rat liver and kidney by tunicamycin decreased the hepatic and renal mRNA and plasma level of EPO. Collectively, ER stress selectively impairs the transcriptional activity of EPO but not of other HIF target genes. This effect is mediated by suppression of EPO 3′-enhancer activity via ATF4 without any direct effect on HIF, indicating that UPR contributes to oxygen-sensing regulation of EPO.
Atmospheric ultrafine particles promote vascular calcification via the NF-κB signaling pathway
Authors: Li Rongsong , Mittelstein David , Kam Winnie , Pakbin Payam , Du Yunfeng , Tintut Yin , Navab Mohamad , Sioutas Constantinos , Hsiai Tzung
Published: December 2012

Exposure to atmospheric fine particulate matter (PM2.5) is a modifiable risk factor of cardiovascular disease. Ultrafine particles (UFP, diameter <0.1 μm), a subfraction of PM2.5, promote vascular oxidative stress and inflammatory responses. Epidemiologic studies suggest that PM exposure promotes vascular calcification. Here, we assessed whether UFP exposure promotes vascular calcification via NF-κB signaling. UFP exposure at 50 μg/ml increased alkaline phosphatase (ALP) activity by 4.4 ± 0.2-fold on day 3 ( n = 3, P < 0.001) and matrix calcification by 3.5 ± 1.7-fold on day 10 ( n = 4, P < 0.05) in calcifying vascular cells (CVC), a subpopulation of vascular smooth muscle cells with osteoblastic potential. Treatment of CVC with conditioned media derived from UFP-treated macrophages (UFP-CM) also led to an increase in ALP activities and matrix calcification. Furthermore, both UFP and UFP-CM significantly increased NF-κB activity, and cotreatment with an NF-κB inhibitor, JSH23, attenuated both UFP- and UFP-CM-induced ALP activity and calcification. When low-density lipoprotein receptor-null mice were exposed to UFP at 359.5 μg/m3 for 10 wk, NF-κB activation and vascular calcification were detected in the regions of aortic roots compared with control filtered air-exposed mice. These findings suggest that UFP promotes vascular calcification via activating NF-κB signaling.
Pulmonary ventilation visualized using hyperpolarized helium-3 and xenon-129 magnetic resonance imaging: differences in COPD and relationship to emphysema
Authors: Kirby Miranda , Svenningsen Sarah , Kanhere Nikhil , Owrangi Amir , Wheatley Andrew , Coxson Harvey O. , Santyr Giles E. , Paterson Nigel A. M. , McCormack David G. , Parraga Grace
Published: December 2012

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 (3He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized 3He and 129Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between 3He and 129Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. 3He and 129Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by 3He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by 3He gas only, mean 3He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm2/s, ADCHX = 0.470 ± 0.125 cm2/s, P < 0.0001). The difference between 3He and 129Xe ventilation volume was significantly correlated with CT HU15% ( r = −65, P = 0.04) and 3He ADCHO ( r = 0.70, P = 0.02), but not CT wall area percentage ( r = −0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased 129Xe MRI ventilation compared with 3He MRI, and these regions of decreased 129Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness.
Effects of eccentric training on mechanical properties of the plantar flexor muscle-tendon complex
Authors: Fouré Alexandre , Nordez Antoine , Cornu Christophe
Published: December 2012

Eccentric training is a mechanical loading classically used in clinical environment to rehabilitate patients with tendinopathies. In this context, eccentric training is supposed to alter tendon mechanical properties but interaction with the other components of the muscle-tendon complex remains unclear. The aim of this study was to determine the specific effects of 14 wk of eccentric training on muscle and tendon mechanical properties assessed in active and passive conditions in vivo. Twenty-four subjects were randomly divided into a trained group ( n = 11) and a control group ( n = 13). Stiffness of the active and passive parts of the series elastic component of plantar flexors were determined using a fast stretch during submaximal isometric contraction, Achilles tendon stiffness and dissipative properties were assessed during isometric plantar flexion, and passive stiffness of gastrocnemii muscles and Achilles tendon were determined using ultrasonography while ankle joint was passively moved. A significant decrease in the active part of the series elastic component stiffness was found ( P < 0.05). In contrast, a significant increase in Achilles tendon stiffness determined under passive conditions was observed ( P < 0.05). No significant change in triceps surae muscles and Achilles tendon geometrical parameters was shown ( P > 0.05). Specific changes in muscle and tendon involved in plantar flexion are mainly due to changes in intrinsic mechanical properties of muscle and tendon tissues. Specific assessment of both Achilles tendon and plantar flexor muscles allowed a better understanding of the functional behavior of the muscle-tendon complex and its adaptation to eccentric training.
Id-1 Is a Key Transcriptional Regulator of Glioblastoma Aggressiveness and a Novel Therapeutic Target
Authors: Soroceanu Liliana , Murase Ryuichi , Limbad Chandani , Singer Eric , Allison Juanita , Adrados Isabel , Kawamura Rumi , Pakdel Arash , Fukuyo Yayoi , Nguyen Daniel , Khan Sabeena , Arauz Robert , Yount Garret L. , Moore Dan H. , Desprez Pierre-Yves , McAllister Sean D.
Published: December 2012

Glioblastoma is the most common form of primary adult brain tumors. A majority of glioblastomas grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control glioblastoma invasiveness and target them therapeutically. We show here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of glioblastoma cell lines and primary glioblastoma cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathologic grades in patient biopsies. Id-1 knockdown dramatically reduces glioblastoma cell invasion that is accompanied by profound morphologic changes and robust reduction in expression levels of “mesenchymal” markers, as well as inhibition of self-renewal potential and downregulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human glioblastoma. Furthermore, we show that a nontoxic compound, cannabidiol, significantly downregulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. In addition, cannabidiol significantly inhibits the invasion of glioblastoma cells through an organotypic brain slice and glioma progression in vivo. Our results suggest that Id-1 regulates multiple tumor-promoting pathways in glioblastoma and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of patients with glioblastoma. Cancer Res; 73(5); 1559–69. ©2012 AACR.
Crizotinib-Resistant NPM-ALK Mutants Confer Differential Sensitivity to Unrelated Alk Inhibitors
Authors: Ceccon Monica , Mologni Luca , Bisson William , Scapozza Leonardo , Gambacorti-Passerini Carlo
Published: December 2012

The dual ALK/MET inhibitor crizotinib was recently approved for the treatment of metastatic and late-stage ALK+ NSCLC, and is currently in clinical trial for other ALK-related diseases. As predicted after other tyrosine kinase inhibitors' clinical experience, the first mutations that confer resistance to crizotinib have been described in patients with non–small cell lung cancer (NSCLC) and in one patient inflammatory myofibroblastic tumor (IMT). Here, we focused our attention on the anaplastic large cell lymphoma (ALCL), where the oncogenic fusion protein NPM-ALK, responsible for 70% to 80% of cases, represents an ideal crizotinib target. We selected and characterized 2 human NPM-ALK+ ALCL cell lines, KARPAS-299 and SUP-M2, able to survive and proliferate at different crizotinib concentrations. Sequencing of ALK kinase domain revealed that a single mutation became predominant at high crizotinib doses in each cell line, namely L1196Q and I1171N in Karpas-299 and SUP-M2 cells, respectively. These mutations also conferred resistance to crizotinib in Ba/F3 cells expressing human NPM-ALK. The resistant cell populations, as well as mutated Ba/F3 cells, were characterized for sensitivity to two additional ALK inhibitors: the dual ALK/EGFR inhibitor AP26113 and NVP-TAE684. While L1196Q-positive cell lines were sensitive to both inhibitors, cells carrying I1171N substitution showed cross-resistance to all ALK inhibitors tested. This study provides potentially relevant information for the management of patients with ALCL that may relapse after crizotinib treatment. Mol Cancer Res; 11(2); 122–32. ©2012 AACR.
Novel Non-Trocar Technique for Laparoscopic Radiofrequency Ablation
Authors: Tsuchida Shinobu , Fukumoto Takumi , Toyokawa Akihiro , Awazu Masahide , Kusunoki Nobuya , Kido Masahiro , Takahashi Masanori , Tanaka Motofumi , Kuramitsu Kaori , Kim Soo Ryang , Ku Yonson , Kudo Masatoshi
Published: December 2012

We have developed a novel insertion method, a non-trocar technique (NTT), for laparoscopic radiofrequency ablation, whereby an ablation needle, guided by a 14.8-mm echo probe (PVM-787LA; Toshiba, Tokyo, Japan), accurately and easily punctures the target tumor in the liver. By existing methods, an ablation needle is inserted into the abdominal cavity through a puncture hole away from the echo probe because of the presence of a 15-mm trocar. Under such circumstances, fitting and sliding an ablation needle along the groove of the probe into the abdominal cavity is difficult because of the longitudinal dissociation between the needle and the probe. To avoid this dissociation, an echo probe is inserted directly through the small incision from which the 12-mm trocar is withdrawn and an ablation needle is introduced directly into the abdominal cavity through a puncture hole adjacent to and slid along the groove of the probe.
Hepatocellular Carcinoma with Obstructive Jaundice: Endoscopic and Percutaneous Biliary Drainage
Authors: Minami Yasunori , Kudo Masatoshi
Published: December 2012

Among patients with later stage hepatocellular carcinoma (HCC), only 1–12% manifest obstructive jaundice as the initial complaint. Endoscopic retrograde biliary drainage (ERBD) and percutaneous transhepatic biliary drainage (PTBD) are the two main non-surgical treatment options for obstructive jaundice in patients with HCC. ERBD is usually the first-line treatment because of its low hemorrhage risk. Some have reported that the successful drainage rate ranges from 72 to 100%. Mean stent patency time and mean survival range from 1.0 to 15.9 and 2.8 to 12.3 months, respectively. PTBD is often an important second-line treatment when ERBD is impossible. With regard to materials, metallic stents offer the benefit of longer patency than plastic stents. The dominant effect of biliary drainage suggests that successful jaundice therapy could enhance anti-cancer treatment by increasing life expectancy, decreasing mortality, or both. We present an overview of the efficacy of endoscopic and percutaneous drainage for obstructive jaundice in patients with HCC who are not candidates for surgical resection and summarize the current indications and outcomes of reported clinical use.
Escin Inhibits Type I Allergic Dermatitis in a Novel Porcine Model
Authors: Sipos Wolfgang , Reutterer Benjamin , Frank Maria , Unger Hermann , Grassauer Andreas , Prieschl-Grassauer Eva , Doerfler Petra
Published: December 2012

Background: Current standard medications for the treatment of allergic inflammation consist primarily of glucocorticoids and anti-histamines, but adverse side effects or insufficient responsiveness by patient subpopulations illustrate the need for safe and novel alternatives. Thus, there is a demand to develop a porcine model that is able to mimic mast cell-mediated type I hypersensitivity. Previously, we found that escin, a pharmacologically active mix of triterpene saponins from horse chestnut extracts, exerts anti-allergic effects in murine models and merits further investigation as an anti-allergic therapeutic. Methods: We developed a new porcine model of allergic dermatitis based on a clinical prick test protocol. Histamine clearly provoked erythema and swelling at the prick site, whereas the mast cell-degranulating compound 48/80 even more pronounced caused wheal and flare reactions known from the human prick response. This model was used to test the anti-allergic efficacy of orally applied escin. Results: Oral pretreatment of animals with escin strongly inhibited the allergic skin response induced by compound 48/80 in a dose-dependent manner. Additional in vitro data from murine mast cells indicate an engagement of the glucocorticoid receptor pathway upon treatment with escin. Conclusions: This model provides a valuable and easy-to-set-up tool for preclinical studies of mast cell-inhibiting compounds. The successful implementation of this model supports the development of oral escin applications as a novel anti-allergic therapy.
A and B Blood Group Antigens in Human Pancreatic Ductal Adenocarcinomas
Authors: Handra-Luca Adriana
Published: December 2012

Objectives: The aim of this study was to determine the clinicopathological significance of blood group expression patterns in patients with surgically resected pancreatic ductal adenocarcinomas. Methods: Pancreatic ductal adenocarcinomas from 459 patients were analyzed for immunohistochemical expression of A and B blood group antigens on tissue microarrays. Correlations were established by Fisher’s test, χ2 test, and logistic regression models, and relationships to postsurgical overall survival were analyzed by Kaplan-Meier method, log-rank test, and multivariate Cox models. Results: Tumors expressing blood group A antigen predicted fewer lymph node metastases (<3) and had longer postoperative survival by univariate and multivariate analysis. Loss of A antigen tumor expression in A blood group type patients correlated to vascular invasion. Conclusion: In patients with resectable pancreatic ductal adenocarcinomas, blood group A antigen expression predicted fewer lymph node metastases and was associated with improved outcome after pancreaticoduodenectomy.
Epidemiologic Evidence of Health Effects from Long-Distance Transit of Chemical Weapons Fallout from Bombing Early in the 1991 Persian Gulf War
Authors: Haley Robert W. , Tuite James J.
Published: December 2012

Background: Military intelligence data published in a companion paper explain how chemical fallout from US and Coalition bombing of Iraqi chemical weapons facilities early in the air campaign transited long distance, triggering nerve agent alarms and exposing US troops. We report the findings of a population-based survey designed to test competing hypotheses on the impact on chronic Gulf War illness of nerve agent from early-war bombing versus post-war demolition. Methods: The US Military Health Survey performed computer-assisted telephone interviews of a stratified random sample of Gulf War-era veterans (n = 8,020). Early-war exposure was measured by having heard nerve agent alarms and post-war exposure, by the computer-generated plume from the Khamisiyah demolition. Gulf War illness was measured by two widely published case definitions. Results: The OR (95% CI) for the association of alarms with the Factor case definition was 4.13 (95% CI 2.51–6.80) compared with 1.21 (95% CI 0.86–1.69) for the Khamisiyah plume. There was a dose-related trend for the number of alarms (ptrend < 0.001) but not for the number of days in the Khamisiyah plume (ptrend = 0.17). Conclusions: Exposure to low-level sarin nerve agent in fallout from bombing early in the air campaign contributed more to chronic illness than post-war demolition.
Thoracic Paravertebral Block for Postoperative Pain Management in Percutaneous Nephrolithotomy Patients: A Randomized Controlled Clinical Trial
Authors: Ak K. , Gursoy S. , Duger C. , Isbir A.C. , Kaygusuz K. , Ozdemir Kol I. , Gokce G. , Mimaroglu C.
Published: December 2012

Objective: To investigate the effect of thoracic paravertebral block (PVB) on pain control and morphine consumption in percutaneous nephrolithotomy operations. Subjects and Methods: This randomized controlled clinical study was performed on 60 American Society of Anesthesiologists (ASA) I-II patients between the ages of 18 and 60 years who underwent percutaneous nephrolithotomy with approval of the ethical committee and written consent of the patients. Patients were randomly allocated into two groups: group P had 4 ml of 0.5% levobupivacaine injected at each of the T10, T11, and T12 paravertebral spaces and a standard PVB, and group C received 4 ml of 0.9% NaCl solution. All patients were given standard general anesthesia. The follow-up of saturation, heart rate, peripheral oxygen, and blood pressure values was recorded before induction, intraoperatively, and postoperatively. At postoperative 1, 2, 6, 12, and 24 h, the visual analog scale (VAS), Ramsey sedation score, respiratory rate, and 24-hour total morphine consumption were recorded. In addition, side effects and satisfaction of patients were recorded. Results: VAS scores and total morphine consumption were lower in group P than in group C: 2.3 vs. 4.3 and 22.3 vs. 43.2 mg, respectively (p < 0.05). The level of satisfaction was higher in group P than group C. Differences between groups in other parameters were not significant. Conclusions: Thoracic PVB with levobupivacaine provided a good postoperative analgesia and increased patient satisfaction for those who underwent percutaneous nephrolithotomy.
Neutrophils, neutrophil extracellular traps and interleukin-17 associate with the organisation of thrombi in acute myocardial infarction
Authors: Li Xiaofei , Teeling Peter , Mackaay Claire , Ploegmakers Hanneke , van der Loos Chris , Daemen Mat , de Winter Robbert , van der Wal Allard , de Boer Onno
Published: December 2012

Neutrophils are important cellular sources of interleukin (IL) 17A and –F. Moreover, upon activation neutrophils are able to excrete chromatin embedded with components from their cytoplasmic granules to form ‘neutrophil extracellular traps’ (NETs). Recent studies suggested that NETs contribute to thrombosis by promoting fibrin deposition and platelet aggregation. IL17A may also promote thrombosis by enhancing platelet aggregation. In the present study we investigated the presence of neutrophils, NETs and IL17A and –F in coronary thrombosuction specimens obtained from patients after acute myocardial infarction. Neutrophils and NETs were identified using histochemical (H&E, Feulgen procedure) and immunohistochemical stainings (Histone H1, myeloperoxidase, neutrophil elastase) in 15 fresh, 15 lytic and 15 organised thrombi. The presence and distribution of IL17A and –F was studied using (immuno)histochemical double staining and spectral image analysis, rtPCR and Western blot. High numbers of neutrophils are present (10–30% of the thrombus mass) in fresh and lytic, but not in organized thrombus. NETs were frequently observed in fresh (4/15) and lytic (12/15), but never in organised thrombus specimens. Double staining combining the Feulgen reaction with Histone- H1, MPO or neutrophil elastase confirmed colocalisation with DNA. Cytoplasmatic IL17A/F staining was found in the majority of the neutrophils, extracellularly and in NETs. Western blotting confirmed the presence of IL17A and IL17F in thrombus specimens. In conclusion, a large burden of neutrophils, neutrophil extracellular traps and IL17A and –F are important constituents of fresh and lytic thrombus after acute myocardial infarction. The specific colocalisation of these indicates a role during thrombus stabilisation and growth.
Replacement therapy for bleeding episodes in factor VII deficiency
Authors: Napolitano Mariasanta , Dolce Alberto , Garrido Rosario Perez , Batorova Angelika , Karimi Mehran , Platokouki Helen , Auerswald Günter , Bertrand Anne-Marie , Di Minno Giovanni , Schved Jean , Bjerre Jens , Ingerslev Jorgen , Sørensen Benny , Ruiz-Saez Arlette , Mariani Guglielmo ,   the Seven Treatment Evaluation Registry (STER) and the International Factor VII Deficiency Study Groups
Published: December 2012

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1–20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one postrFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single ‘intermediate’ doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.
Prevalence of thrombocytosis in critically ill patients and its association with symptomatic acute pulmonary embolism
Authors: Chavan Shaila , Ho Kwok
Published: December 2012

It is uncertain whether thrombocytosis without underlying myeloproliferative diseases is associated with an increased risk of acute pulmonary embolism (PE). We investigated the relationship between thrombocytosis and risk of symptomatic acute PE, and whether Pulmonary Embolism Severity Index (PESI) was reliable in predicting mortality of acute PE. This multicentre registry study involved a total of 609,367 critically ill patients admitted to 160 intensive care units (ICUs) in Australia or New Zealand between 2006 and 2011. Forward stepwise logistic regression was used to assess the relationship between risk of acute PE and platelet counts on intensive care unit (ICU) admission. Acute PE (n=3387) accounted for 0.9% of all emergency ICU admissions. Over 20% of all PE required mechanical ventilation, 4.2% had cardiac arrest, and the mortality was high (14.8%). Thrombocytosis, defined by a platelet count >500×109 per litre, occurred in 2.1% of the patients and was more common in patients with acute PE than other diagnoses (3.4 vs. 2.0%). The platelet counts explained about 4.5% of the variability and had a linear relationship with the risk of acute PE (odds ratio 1.19 per 100×109 per litre increment in platelet count, 95% confidence interval 1.06–1.34), after adjusting for other covariates. The PESI had a reasonable discriminative ability (area under receiver-operating-characteristic curve = 0.78) and calibration to predict mortality across a wide range of severity of acute PE. In summary, thrombocytosis was associated with an increased risk of symptomatic acute PE. PESI was useful in predicting mortality across a wide range of severity of acute PE.
Aggregated Low-Density Lipoprotein Induces LRP1 Stabilization Through E3 Ubiquitin Ligase CHFR Downregulation in Human Vascular Smooth Muscle Cells
Authors: Cal Roi , García-Arguinzonis Maisa , Revuelta-López Elena , Castellano José , Padró Teresa , Badimon Lina , Llorente-Cortés Vicenta
Published: December 2012

Objective—

Low density lipoprotein retention and aggregation in the arterial intima are key processes in atherogenesis. Aggregated LDL (agLDL) is taken up through low-density lipoprotein receptor-related protein 1 (LRP1) by human vascular smooth muscle cells (VSMC). AgLDL increases LRP1 expression, at least in part, by downregulation of sterol regulatory element-binding proteins. It is unknown whether agLDL has some effect on the ubiquitin-proteasome system, and therefore on the LRP1 receptor turnover. The objective of this study was to analyze the effect of agLDL on the degradation of LRP1 by the ubiquitin-proteasome system in human VSMC.

Methods and Results—

Human VSMC were isolated from the media of human coronary arteries. Ubiquitinylated LRP1 protein levels were significantly reduced in human VSMC exposed to agLDL (100 μg/mL) for 20 hours (agLDL: 3.70±0.44 a.u. versus control: 9.68±0.55 a.u). Studies performed with cycloheximide showed that agLDL prolongs the LRP1 protein half life. Pulse-chase analysis showed that LRP1 turnover rate is reduced in agLDL-exposed VSMC. Two-dimensional electrophoresis shows an alteration in the proteomic profile of a RING type E3 ubiquitin ligase, CHFR. Real-time PCR and Western blot analysis showed that agLDL (100 μg/mL) decreased the transcriptional and protein expression of CHFR. CHFR silencing increased VSMC, but not macrophage, LRP1 expression. However, CHFR silencing did not exert any effect on the classical low-density lipoprotein receptor protein levels. Furthermore, immunoprecipitation experiments demonstrated that the physical interaction between CHFR and LRP1 decreased in the presence of agLDL.

Conclusion—

Our results demonstrate that agLDL prolongs the half life of LRP1 by preventing the receptor ubiquitinylation, at least in part, through CHFR targeting. This mechanism seems to be specific for LRP1 and VSMC.
Platelet IκB Kinase-β Deficiency Increases Mouse Arterial Neointima Formation via Delayed Glycoprotein Ibα Shedding
Authors: Wei Shujian , Wang Huan , Zhang Guoying , Lu Ying , An Xiaofei , Ren Shumei , Wang Yunmei , Chen Yuguo , White James G. , Zhang Chunxiang , Simon Daniel I. , Wu Chaodong , Li Zhenyu , Huo Yuqing
Published: December 2012

Objective—

On the luminal surface of injured arteries, platelet activation and leukocyte–platelet interactions are critical for the initiation and progression of arterial restenosis. The transcription factor nuclear factor-κB is a critical molecule in platelet activation. Here, we investigated the role of the platelet nuclear factor-κB pathway in forming arterial neointima after arterial injury.

Methods and Results—

We performed carotid artery wire injuries in low-density lipoprotein receptor-deficient (LDLR
–/–
) mice with a platelet-specific deletion of IκB kinase-β (IKKβ) (IKKβ
fl/fl
/PF4
cre
/LDLR
–/–
) and in control mice (IKKβ
fl/fl
/LDLR
–/–
). The size of the arterial neointima was 61% larger in the IKKβ
fl/fl
/PF4
cre
/LDLR
–/–
mice compared with the littermate control IKKβ
fl/fl
/LDLR
–/–
mice. Compared with the control mice, the IKKβ
fl/fl
/PF4
cre
/LDLR
–/–
mice exhibited more leukocyte adhesion at the injured area. The extent of glycoprotein Ibα shedding after platelet activation was compromised in the IKKβ-deficient platelets. This effect was associated with a low level of the active form of A Disintegrin And Metalloproteinase 17, the key enzyme involved in mediating glycoprotein Ibα shedding in activated IKKβ-deficient platelets.

Conclusion—

Platelet IKKβ deficiency increases the formation of injury-induced arterial neointima formation. Thus, nuclear factor-κB–related inhibitors should be carefully evaluated for use in patients after an arterial intervention.
Incremental Value of the Preoperative Echocardiogram to Predict Mortality and Major Morbidity in Coronary Artery Bypass Surgery
Authors: Afilalo Jonathan , Flynn Aidan W. , Shimony Avi , Rudski Lawrence G. , Agnihotri Arvind K. , Morin Jean-Francois , Castrillo Cristina , Shahian David M. , Picard Michael H.
Published: December 2012

Background—

Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram.

Methods and Results—

Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivation and validation cohorts. A panel of quantitative echocardiographic parameters was measured. Clinical variables were extracted from the Society of Thoracic Surgeons database. The primary outcome was in-hospital mortality or major morbidity, and the secondary outcome was long-term all-cause mortality. The derivation cohort consisted of 667 patients with a mean age of 67.2±11.1 years and 22.8% females. The following echocardiographic parameters were found to be optimal predictors of mortality or major morbidity: severe diastolic dysfunction, as evidenced by restrictive filling (odds ratio, 2.96; 95% confidence interval, 1.59-5.49), right ventricular dysfunction, as evidenced by fractional area change <35% (odds ratio, 3.03; 95% confidence interval, 1.28-7.20), or myocardial performance index >0.40 (odds ratio, 1.89; 95% confidence interval, 1.13-3.15). These results were confirmed in the validation cohort of 187 patients. When added to the Society of Thoracic Surgeons risk score, the echocardiographic parameters resulted in a net improvement in model discrimination and reclassification with a change in c-statistic from 0.68 to 0.73 and an integrated discrimination improvement of 5.9% (95% confidence interval, 2.8%-8.9%). In the Cox proportional hazards model, right ventricular dysfunction and pulmonary hypertension were independently predictive of mortality over 3.2 years of follow-up.

Conclusions—

Preoperative echocardiography, in particular right ventricular dysfunction and restrictive left ventricular filling, provides incremental prognostic value in identifying patients at higher risk of mortality or major morbidity after coronary artery bypass surgery.
Clipping Versus Coiling for Ruptured Intracranial Aneurysms
Authors: Li Hui , Pan Rui , Wang Hongxuan , Rong Xiaoming , Yin Zi , Milgrom Daniel P. , Shi Xiaolei , Tang Yamei , Peng Ying
Published: December 2012

Background and Purpose—

Endovascular treatment has increasingly been used for aneurismal subarachnoid aneurismal hemorrhage. The aim of this analysis is to assess the current evidence regarding safety and efficiency of clipping compared with coiling.

Methods—

We conducted a meta-analysis of studies that compared clipping with coiling between January 1999 and July 2012. Comparison of binary outcomes between treatment groups was described using odds ratios (OR; clip versus coil).

Results—

Four randomized controlled trials and 23 observational studies were included. Randomized controlled trials showed that coiling reduced the 1-year unfavorable outcome rate (OR, 1.48; 95% confidence interval [CI], 1.24–1.76). However, there was no statistical deference in nonrandomized controlled trials (OR, 1.11; 95% CI, 0.96–1.28). Subgroup analysis revealed coiling yielded better outcomes for patients with good preoperative grade (OR, 1.51; 95% CI, 1.24–1.84) than for poor preoperative patients (OR, 0.88; 95% CI 0.56–1.38). Additionally, the incidence of rebleeding is higher after coiling (OR, 0.43; 95% CI, 0.28–0.66), corresponding to a better complete occlusion rate of clipping (OR, 2.43; 95% CI, 1.88–3.13). The 1-year mortality showed no significant difference (OR, 1.07; 95% CI, 0.88–1.30). Vasospasm was more common after clipping (OR, 1.43; 95% CI, 1.07–1.91), whereas the ischemic infarct (OR, 0.74; 95% CI, 0.52–1.06), shunt-dependent hydrocephalus (OR, 0.84; 95% CI, 0.66–1.07), and procedural complication rates (OR, 1.19; 95% CI, 0.67–2.11) did not differ significantly between techniques.

Conclusions—

Coiling yields a better clinical outcome, the benefit being greater in those with a good preoperative grade than those with a poor preoperative grade. However, coiling leads to a greater risk of rebleeding. Well-designed randomized trials with special considerations to the aspect are needed.