bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing preclinical models of ischemic heart failure: differences between LAD and LCx infarctions
Authors: Ishikawa Kiyotake , Aguero Jaume , Tilemann Lisa , Ladage Dennis , Hammoudi Nadjib , Kawase Yoshiaki , Santos-Gallego Carlos G. , Fish Kenneth , Levine Robert A. , Hajjar Roger J.
Published: September 2014

Large animal studies are an important step toward clinical translation of novel therapeutic approaches. We aimed to establish an ischemic heart failure (HF) model with a larger myocardial infarction (MI) relative to previous studies, and characterize the functional and structural features of this model. An MI was induced by occluding the proximal left anterior descending artery (LAD; n = 15) or the proximal left circumflex artery (LCx; n = 6) in Yorkshire pigs. Three pigs with sham procedures were also included. All pigs underwent hemodynamic and echocardiographic assessments before MI, at 1 mo, and 3 mo after MI. Analyses of left ventricular (LV) myocardial mechanics by means of strains and torsion were performed using speckle-tracking echocardiography and compared between the groups. The proximal LAD MI approach induced larger infarct sizes (14.2 ± 3.2% vs. 10.6 ± 1.9%, P = 0.03), depressed systolic function (LV ejection fraction; 39.8 ± 7.5% vs. 54.1 ± 4.6%, P < 0.001), and more LV remodeling (end-systolic volume index; 82 ± 25 ml/m2 vs. 51 ± 18 ml/m2, P = 0.02, LAD vs. LCx, respectively) compared with the LCx MI approach without compromising the survival rate. At the papillary muscle level, echocardiographic strain analysis revealed no differences in radial and circumferential strain between LAD and LCx MIs. However, in contrast with the LCx MI, the LAD MI resulted in significantly decreased longitudinal strain. The proximal LAD MI model induces more LV remodeling and depressed LV function relative to the LCx MI model. Location of MI significantly impacts the severity of HF, thus careful consideration is required when choosing an MI model for preclinical HF studies.
Chronic exposure to perfluorinated compounds: Impact on airway hyperresponsiveness and inflammation
Authors: Ryu Min H. , Jha Aruni , Ojo Oluwaseun O. , Mahood Thomas H. , Basu Sujata , Detillieux Karen A. , Nikoobakht Neda , Wong Charles S. , Loewen Mark , Becker Allan B. , Halayko Andrew J.
Published: September 2014

Emerging epidemiological evidence reveals a link between lung disease and exposure to indoor pollutants such as perfluorinated compounds (PFCs). PFC exposure during critical developmental stages may increase asthma susceptibility. Thus, in a murine model, we tested the hypothesis that early life and continued exposure to two ubiquitous household PFCs, perfluorooctanoic acid (PFOA) and perflurooctanesulfonic acid (PFOS), can induce lung dysfunction that exacerbates allergen-induced airway hyperresponsiveness (AHR) and inflammation. Balb/c mice were exposed to PFOA or PFOS (4 mg/kg chow) from gestation day 2 to 12 wk of age by feeding pregnant and nursing dams, and weaned pups. Some pups were also sensitized and challenged with ovalbumin (OVA). We assessed lung function and inflammatory cell and cytokine expression in the lung and examined bronchial goblet cell number. PFOA, but not PFOS, without the OVA sensitization/challenge induced AHR concomitant with a 25-fold increase of lung macrophages. PFOA exposure did not affect OVA-induced lung inflammatory cell number. In contrast, PFOS exposure inhibited OVA-induced lung inflammation, decreasing total cell number in lung lavage by 68.7%. Interferon-γ mRNA in the lung was elevated in all PFC-exposed groups. Despite these effects, neither PFOA nor PFOS affected OVA-induced AHR. Our data do not reveal PFOA or PFOS exposure as a risk factor for more severe allergic asthma-like symptoms, but PFOA alone can induce airway inflammation and alter airway function.
MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle
Authors: Comer Brian S. , Camoretti-Mercado Blanca , Kogut Paul C. , Halayko Andrew J. , Solway Julian , Gerthoffer William T.
Published: September 2014

MicroRNA (miR)-146a and miR-146b are negative regulators of inflammatory gene expression in lung fibroblasts, epithelial cells, monocytes, and endothelial cells. The abundance of cyclooxygenase-2 (COX-2) and IL-1β is negatively regulated by the miR-146 family, suggesting miR-146a and/or miR-146b might modulate inflammatory mediator expression in airway smooth muscle thereby contributing to pathogenesis of asthma. To test this idea we compared miR-146a and miR-146b expression in human airway smooth muscle cells (hASMCs) from nonasthmatic and asthmatic subjects treated with cytomix (IL-1β, TNF-α, and IFNγ) and examined the miRNAs' effects on COX-2 and IL-1β expression. We found that cytomix treatment elevated miR-146a and miR-146b abundance. Induction with cytomix was greater than induction with individual cytokines, and asthmatic cells exhibited higher levels of miR-146a expression following cytomix treatment than nonasthmatic cells. Transfection of miR-146a or miR-146b mimics reduced COX-2 and IL-1β expression. A miR-146a inhibitor increased COX-2 and IL-1β expression, but a miR-146b inhibitor was ineffective. Repression of COX-2 and IL-1β expression by miR-146a correlated with reduced abundance of the RNA-binding protein human antigen R. These results demonstrate that miR-146a and miR-146b expression is inducible in hASMCs by proinflammatory cytokines and that miR-146a expression is greater in asthmatic cells. Both miR-146a and miR-146b can negatively regulate COX-2 and IL-1β expression at pharmacological levels, but loss-of-function studies showed that only miR-146a is an endogenous negative regulator in hASMCs. The results suggest miR-146 mimics may be an attractive candidate for further preclinical studies as an anti-inflammatory treatment of asthma.
Mathematical Modeling of Tumor Growth and Metastatic Spreading: Validation in Tumor-Bearing Mice
Authors: Hartung Niklas , Mollard Séverine , Barbolosi Dominique , Benabdallah Assia , Chapuisat Guillemette , Henry Gerard , Giacometti Sarah , Iliadis Athanassios , Ciccolini Joseph , Faivre Christian , Hubert Florence
Published: September 2014

Defining tumor stage at diagnosis is a pivotal point for clinical decisions about patient treatment strategies. In this respect, early detection of occult metastasis invisible to current imaging methods would have a major impact on best care and long-term survival. Mathematical models that describe metastatic spreading might estimate the risk of metastasis when no clinical evidence is available. In this study, we adapted a top-down model to make such estimates. The model was constituted by a transport equation describing metastatic growth and endowed with a boundary condition for metastatic emission. Model predictions were compared with experimental results from orthotopic breast tumor xenograft experiments conducted in Nod/Scidγ mice. Primary tumor growth, metastatic spread and growth were monitored by 3D bioluminescence tomography. A tailored computational approach allowed the use of Monolix software for mixed-effects modeling with a partial differential equation model. Primary tumor growth was described best by Bertalanffy, West, and Gompertz models, which involve an initial exponential growth phase. All other tested models were rejected. The best metastatic model involved two parameters describing metastatic spreading and growth, respectively. Visual predictive check, analysis of residuals, and a bootstrap study validated the model. Coefficients of determination were $R^2 = 0.94$ for primary tumor growth and $R^2 = 0.57$ for metastatic growth. The data-based model development revealed several biologically significant findings. First, information on both growth and spreading can be obtained from measures of total metastatic burden. Second, the postulated link between primary tumor size and emission rate is validated. Finally, fast growing peritoneal metastases can only be described by such a complex partial differential equation model and not by ordinary differential equation models. This work advances efforts to predict metastatic spreading during the earliest stages of cancer. Cancer Res; 74(22); 6397–407. ©2014 AACR.
A Small-Molecule Modulator of the Tumor-Suppressor miR34a Inhibits the Growth of Hepatocellular Carcinoma
Authors: Xiao Zhangang , Li Chi Han , Chan Stephen L. , Xu Feiyue , Feng Lu , Wang Yan , Jiang Jian-Dong , Sung Joseph J.Y. , Cheng Christopher H.K. , Chen Yangchao
Published: September 2014

Small molecules that restore the expression of growth-inhibitory microRNAs (miRNA) downregulated in tumors may have potential as anticancer agents. miR34a functions as a tumor suppressor and is downregulated or silenced commonly in a variety of human cancers, including hepatocellular carcinoma (HCC). In this study, we used an HCC cell–based miR34a luciferase reporter system to screen for miR34a modulators that could exert anticancer activity. One compound identified as a lead candidate, termed Rubone, was identified through its ability to specifically upregulate miR34a in HCC cells. Rubone activated miR34a expression in HCC cells with wild-type or mutated p53 but not in cells with p53 deletions. Notably, Rubone lacked growth-inhibitory effects on nontumorigenic human hepatocytes. In a mouse xenograft model of HCC, Rubone dramatically inhibited tumor growth, exhibiting stronger anti-HCC activity than sorafenib both in vitro and in vivo. Mechanistic investigations showed that Rubone decreased expression of cyclin D1, Bcl-2, and other miR34a target genes and that it enhanced the occupancy of p53 on the miR34a promoter. Taken together, our results offer a preclinical proof of concept for Rubone as a lead candidate for further investigation as a new class of HCC therapeutic based on restoration of miR34a tumor-suppressor function. Cancer Res; 74(21); 6236–47. ©2014 AACR.
Pro-Oncogenic Role of Alternative p38 Mitogen-Activated Protein Kinases p38γ and p38δ, Linking Inflammation and Cancer in Colitis-Associated Colon Cancer
Authors: del Reino Paloma , Alsina-Beauchamp Dayanira , Escós Alejandra , Cerezo-Guisado Ma Isabel , Risco Ana , Aparicio Noelia , Zur Rafal , Fernandez-Estévez Marian , Collantes Elena , Montans Jose , Cuenda Ana
Published: September 2014

p38 MAPK signaling has been implicated in the regulation of processes leading to cancer development and progression. Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association remains largely unknown. The related p38αMAPK (MAPK14) proteins p38γ (MAPK12) and p38δ (MAPK13) were recently shown to modulate the immune response, although their role in tumorigenesis remains controversial and their function in inflammation-associated cancer has not been studied. We analyzed the role of p38γ and p38δ in colon cancer associated to colitis using the azoxymethane/dextran sodium sulphate (AOM/DSS) colitis-associated colon cancer model in wild-type (WT), p38γ-, p38δ-, and p38γ/δ-deficient (p38γ/δ−/−) mice. We found that p38γ/δ deficiency significantly decreased tumor formation, in parallel with a decrease in proinflammatory cytokine and chemokine production. Analysis of leukocyte populations in p38γ/δ−/− mouse colon showed less macrophage and neutrophil recruitment than in WT mice. Furthermore, WT chimeric mice with transplanted p38γ/δ−/− bone marrow had less tumors than WT mice transplanted with WT bone marrow, whereas tumor number was significantly increased in p38γ/δ−/− chimeric mice with WT bone marrow compared with p38γ/δ−/− mice transplanted with p38γ/δ−/− bone marrow. Together, our results establish that p38γ and p38δ are central to colitis-associated colon cancer formation through regulation of hematopoietic cell response to injury, and validate p38γ and p38δ as potential targets for cancer therapy. Cancer Res; 74(21); 6150–60. ©2014 AACR.
Prevalence, Incidence, Clearance, and Associated Factors of Genital Human Papillomavirus Infection among Men: A Population-Based Cohort Study in Rural China
Authors: Liu Mengfei , He Zhonghu , Zhang Chanyuan , Liu Fangfang , Liu Ying , Li Jingjing , Xu Zhongyao , Wang Qiyan , Hang Dong , Shen Na , Pan Yaqi , Guo Chuanhai , Cai Hong , Ke Yang
Published: September 2014

Background: The natural history of human papillomavirus (HPV) infection in men on a population base has rarely been studied in general, particularly among Chinese men.

Methods: A total of 1,286 men ages 25 to 65 years from rural China were enrolled during 2009–2010 and their genital HPV infection status was assessed biannually for up to seven visits using PCR and sequencing methods. Prevalence analysis was performed among men with at least one valid HPV result (N = 1,279) and men with at least two consecutive HPV results (N = 1,059) were included in incidence and clearance analyses (median follow-up time, 31.8 months; interquartile range, 15.4–37.9 months).

Results: The prevalence and incidence of any HPV type, oncogenic, and nononcogenic HPV were 17.8%, 6.4%, 12.4%, and 14.6, 4.9, 10.8 per 1,000 person months, respectively. The median duration of infection with any HPV type, oncogenic, and nononcogenic HPV was 11.5, 6.8, and 11.5 months, respectively. The number of lifetime sexual partners was consistently associated with increased risk of prevalent and incident infection of HPV. Men ages 25 to 50 years had a higher incidence and longer duration of HPV infection than older men (51–65 years).

Conclusions and Impact: This epidemiologic investigation provides basic information of genital HPV infection among the Chinese male population; these data are crucial for the consideration of primary strategies against HPV-related carcinoma in the Chinese male and female population. Cancer Epidemiol Biomarkers Prev; 23(12); 2857–65. ©2014 AACR.
Deoxycytidine Kinase Expression Underpins Response to Gemcitabine in Bladder Cancer
Authors: Kerr Martin , Scott Helen E. , Groselj Blaz , Stratford Michael R.L. , Karaszi Katalin , Sharma Naomi L. , Kiltie Anne E.
Published: September 2014

Purpose: In a recent phase II clinical trial, low-dose (100 mg/m2) gemcitabine showed promise as a radiosensitizer in bladder cancer, but underlying mechanisms lack elucidation. Here, we investigated the mechanism of radiosensitization by low-dose gemcitabine in bladder cancer cell lines.

Experimental Design: Four bladder cancer cell lines were screened for radiosensitization by low-dose gemcitabine using clonogenic assay, and gemcitabine-resistant RT112gem and CALgem cells created by exposure to increasing gemcitabine doses. Four key gemcitabine-regulatory genes were knocked down by transient siRNA. Nude mice carrying CALgem subcutaneous xenografts were exposed to 100 mg/kg gemcitabine ± ionizing radiation (IR) and response assessed by tumor growth delay.

Results: Gemcitabine was cytotoxic in the low nanomolar range (10–40 nmol/L) in four bladder cancer cell lines and radiosensitized all four lines. Sensitizer enhancement ratios at 10% survival were: RT112 1.42, CAL29 1.55, T24 1.63, and VMCUB1 1.47. Transient siRNA knockdown of deoxycytidine kinase (dCK) significantly reduced radiosensitization by gemcitabine (P = 0.02). RT112gem and CALgem cells displayed robust decreases of dCK mRNA and protein levels; reexpression of dCK restored gemcitabine sensitivity. However, CALgem xenografts responded better to combination gemcitabine/IR than either treatment alone (P < 0.001) with dCK strongly expressed in the tumor vasculature and stroma.

Conclusions: Gemcitabine resistance in bladder cancer cell lines was associated with decreased dCK expression, but gemcitabine-resistant xenografts were responsive to combination low-dose gemcitabine/IR. We propose that dCK activity in tumor vasculature renders it gemcitabine sensitive, which is sufficient to invoke a tumor response and permit tumor cell kill in gemcitabine-resistant tumors. Clin Cancer Res; 20(21); 5435–45. ©2014 AACR.
Subacute Motor Neuron Hyperexcitability with Mercury Poisoning: A Case Series and Literature Review
Authors: Zhou Zhibin , Zhang Xingwen , Cui Fang , Liu Ruozhuo , Dong Zhao , Wang Xiaolin , Yu Shengyuan
Published: September 2014

Motor neuron hyperexcitability (MNH) indicates a disorder characterized by an ectopic motor nerve discharge on electromyogram (EMG). Here, we present a series of three cases of subacute MNH with mercury poisoning. The first case showed hyperhidrosis, insomnia, generalied myokymia, cramps, tremor, weight loss, and myokymic and neuromyotonic discharges, followed by encephalopathy with confusion, hallucinations, and memory decrease. The second case was similar to the former but without encephalopathic features. The third case showed widespread fasciculation, fatigue, insomnia, weight loss, and autonomic dysfunction, including constipation, micturition difficulty, and impotence, with multiple fibrillation, unstable fasciculation, widened motor neuron potential, and an incremental response at high-rate stimulation in repetitive nerve stimulation. Based on the symptoms, the three cases were diagnosed as Morvan's syndrome, Isaacs' syndrome, and Lambert-Eaton myasthenic syndrome with ALS-like syndrome, respectively. Mercury poisoning in the three cases was confirmed by analysis of blood and urine samples. All cases recovered several months after chelation therapy and were in good condition at follow-up. Very few cases of MNH linked with mercury exposure have been reported in the literature. The mechanism of mercury-induced MNH may be associated with ion channel dysfunction.
Airway Wall Remodeling in Young and Adult Rats with Experimentally Provoked Bronchial Asthma
Authors: Uhlík Jiří , Šimůnková Petra , Žaloudíková Marie , Partlová Simona , Jarkovský Jiří , Vajner Luděk
Published: September 2014

Background: Airway wall remodeling is a typical finding in patients suffering from bronchial asthma. While morphological changes have been thoroughly described in adults, less is known about such changes in children because of the limited accessibility of relevant material. To overcome this constraint, animal asthma models may be used instead of human specimens. This study examined rats with artificially stimulated chronic asthma-like symptoms. Methods: Brown Norway rats of two age categories (young and adult) were sensitized by ovalbumin (OA), and their intrapulmonary airways (IA) were studied using morphometric and histochemical methods. Results: OA administration induced a significant increase in lung resistance in young animals but not in adults. The total IA wall area was significantly increased in both young and adult OA rats. In young animals, thickening of the adventitia played a more crucial role in this increase than it did in adults, in which the mucosa and the submucosa participated to a higher degree. The IA walls of young OA rats had significantly higher levels of infiltrating eosinophils than those of adult OA animals. The multiplication of goblet cells was more pronounced in adult rats, which was associated with a tendency to produce a higher proportion of acidic glycoconjugates. Conclusions: OA stimulation affected the IA of young rats differently than those of adult animals. Changes in the outer IA layer of young rats can be triggered by activated eosinophils; however, stimulated airway epithelium can be a source of factors that influence the inner IA layers in adult rats.
Erfolgreiche endoskopische Neuraltherapie eines Patienten mit chronischem Schmerzsyndrom bei Zustand nach Rektumschussverletzung
Authors: Saha Felix J. , Komhard Volker , Langhorst Jost
Published: September 2014

Hintergrund: Wir berichten über einen 39-jährigen Patienten, der bei einer Auseinandersetzung einen abdominellen Durchschuss mit einer Rektumverletzung erlitt und über persistierend starke Schmerzen während und bis zu 30 min nach der Defäkation berichtete. Ambulante Therapien über einen Zeitraum von über 10 Jahren mit analgetischen, glukokortikoidhaltigen und salicylathaltigen Medikamenten erbrachten keine Besserung der Beschwerden. Falldarstellung: Im Rahmen einer flexiblen Rektoskopie erfolgte eine Neuraltherapie in Form einer lokalen Infiltration der Narbe des Schusskanals im Rektum mittels Procain. Der Patient beschrieb bei Applikation einen starken Injektionsschmerz, der etwa 5-10 s anhielt. Im Anschluss an die Behandlung bestand bei der Defäkation völlige Schmerz-freiheit, die auch zum Entlassungszeitpunkt anhielt. Schlussfolgerung: Der Fallbericht beschreibt erstmals die Anwendung einer endoskopischen Neuraltherapie und gibt Hinweise auf die Wirksamkeit dieser Therapieform bei lang anhaltenden therapierefraktären Beschwerden, deren fokale Ursache im Bereich des Intestinums liegt.
Human Atrial Fibrillation Initiates via Organized Rather Than Disorganized Mechanisms
Authors: Schricker Amir A. , Lalani Gautam G. , Krummen David E. , Rappel Wouter-Jan , Narayan Sanjiv M.
Published: September 2014

Background—

It is unknown how atrial fibrillation (AF) is actually initiated by triggers. Based on consistencies in atrial structure and function in individual patients between episodes of AF, we hypothesized that human AF initiates when triggers interact with deterministic properties of the atria and may engage organized mechanisms.

Methods and Results—

In 31 patients with AF, we mapped AF initiation after spontaneous triggers or programmed stimulation. We used 64-pole basket catheters to measure regional dynamic conduction slowing and to create biatrial activation maps during transitions to AF. Sixty-two AF initiations were recorded (spontaneous, n=28; induced, n=34). Notably, AF did not initiate by disorganized mechanisms, but by either a dominant reentrant spiral wave (76%) or a repetitive focal driver. Both mechanisms were located 21±17 mm from their triggers. AF-initiating spirals formed at the site showing the greatest rate-dependent slowing in each patient. Accordingly, in 10 of 12 patients with multiple observed AF episodes, AF initiated using spatially conserved mechanisms despite diverse triggers.

Conclusions—

Human AF initiates from triggers by organized rather than disorganized mechanisms, either via spiral wave re-entry at sites of dynamic conduction slowing or via repetitive focal drivers. The finding that diverse triggers initiate AF at predictable, spatially conserved functional sites in each individual provides a novel deterministic paradigm for AF with therapeutic implications.
Idiopathic Ventricular Arrhythmia Originating From the Cardiac Crux or Inferior Septum
Authors: Kawamura Mitsuharu , Gerstenfeld Edward P. , Vedantham Vasanth , Rodrigues Derek M. , Burkhardt J. David , Kobayashi Youichi , Hsia Henry H. , Marcus Gregory M. , Marchlinski Francis E. , Scheinman Melvin M. , Badhwar Nitish
Published: September 2014

Background—

Idiopathic ventricular arrhythmia (VA) can arise from the epicardium near the posteroseptal region (cardiac crux). There are only 2 prior reports describing idiopathic VA from the cardiac crux. The purpose of this study was to characterize the clinical and the electrocardiographic features of idiopathic crux VA.

Methods and Results—

Crux VA was identified in 18 patients undergoing catheter ablation. We divided patients into 2 groups, those with VA originating from the apical crux (n=9) and the basal crux (n=9). We described the clinical and electrocardiographic characteristics of crux VA as well as the ablation results. Furthermore, we compared clinical features of crux VA with other sites of idiopathic VA. Fifteen crux VA patients (83%) had sustained ventricular tachycardia and 3 patients required implantable cardioverter defibrillator implantation because of syncope. All patients had a left superior axis and 16 patients had R>S wave in V2. In apical crux VA, all patients had a deep S wave in V6 and 8 patients (89%) had R>S wave in aVR. All apical crux patients underwent attempted ablation in the middle cardiac vein without success. In 4 of these patients, epicardial ablation with subxiphoid approach was performed successfully. All basal crux VA patients had either negative or isoelectric pattern in V1 and had R>S in V6. Patients had successful ablation within the middle cardiac vein.

Conclusions—

Apical versus basal crux VA is identified as a new category of idiopathic VA with distinctive electrocardiographic characteristics; ablation via the middle cardiac vein is effective for eliminating basal crux VA, whereas apical crux VA often requires a subxiphoid epicardial approach.
History of Atrial Fibrillation as a Risk Factor in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Oluleye Oludamilola W. , Rector Thomas S. , Win Sithu , McMurray John J.V. , Zile Michael R. , Komajda Michel , McKelvie Robert S. , Massie Barry , Carson Peter E. , Anand Inder S.
Published: September 2014

Background—

Atrial fibrillation (AFib) is common in heart failure (HF) with preserved ejection fraction (HFpEF). Current AFib stroke risk prediction models include the presence of HF but do not specifically include HFpEF as a risk factor. Whether a history of AFib should be used to identify patients with HFpEF who are at risk has not been established.

Methods and Results—

Baseline characteristics and outcomes of patients with HFpEF in the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial were analyzed in relation to AFib. At baseline, 1209 (29.3%) had a history of AFib. Of these 557 (13.5%) had history of AFib alone, whereas 670 (16.2%) had both a history and AFib on ECG; 2901 (70.3%) had neither. There were no significant differences in the risk of stroke between the 2 groups with a history of AFib who did or did not have AFib present on baseline ECG. During a median follow-up of 53 months, a fatal or nonfatal stroke occurred in 6.5% (79/1209) patients with history of AFib compared with 3.9% (114/2901) with no AFib. Having a history of AFib was independently associated with higher risk of stroke (hazard ratio, 2.2; 95% confidence interval, 1.6–3.2;
P
<0.0001) compared with those with no history of AFib.

Conclusions—

In patients with HFpEF, a history of AFib was common and independently associated with increased risk of stroke, regardless of whether AFib was present on ECG. Patients with HFpEF and a history of AFib should be considered at risk. Further studies are needed to determine whether this risk can be safely reduced.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT000095238.
MHC Class II–Restricted Antigen Presentation by Plasmacytoid Dendritic Cells Drives Proatherogenic T Cell Immunity
Authors: Sage Andrew P. , Murphy Deirdre , Maffia Pasquale , Masters Leanne M. , Sabir Suleman R. , Baker Lauren L. , Cambrook Helen , Finigan Alison J. , Ait-Oufella Hafid , Grassia Gianluca , Harrison James E. , Ludewig Burkhard , Reith Walter , Hansson Göran K. , Reizis Boris , Hugues Stéphanie , Mallat Ziad
Published: September 2014

Background—

Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive.

Methods and Results—

Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using
CD11c
-Cre ×
Tcf4
–/flox
bone marrow transplanted into
Ldlr
–/–
mice. Compared with control
Ldlr
–/–
chimeric mice,
CD11c
-Cre ×
Tcf4
–/flox
mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric
Ldlr
–/–
mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100–specific CD4
+
T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell–derived interferon-γ and lesional T cell infiltration, and was abrogated in CD4
+
T cell–depleted animals.

Conclusions—

This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity.
Increased Levels of Copeptin Before Clinical Diagnosis of Preeclampsia
Authors: Yeung Edwina H. , Liu Aiyi , Mills James L. , Zhang Cuilin , Männistö Tuija , Lu Zhaohui , Tsai Michael Y. , Mendola Pauline
Published: September 2014

Copeptin, a surrogate biomarker of vasopressin, has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia. We measured serum copeptin using samples collected longitudinally during pregnancy among unaffected controls (n=136) and cases of preeclampsia (n=169), gestational diabetes mellitus (n=92), gestational hypertension (n=101), and preterm birth (n=86) in the Calcium for Preeclampsia Prevention trial (1992–1995). Preeclampsia and gestational hypertension were defined as having a diastolic blood pressure ≥90 mm Hg on 2 occasions with and without proteinuria, respectively. The risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age, race, body mass index, insurance status, marital status, current smoking, and clinical site. Baseline copeptin levels, at mean 16 weeks of gestation, were associated with increased preeclampsia risk (adjusted odds ratios and 95% confidence interval being 1.55 per log unit; 1.03–2.31) when compared with controls (
P
=0.03). The association was stronger among cases diagnosed before 37 weeks (1.86; 1.08–3.20) than those diagnosed later (1.45; 0.91–2.32). Copeptin levels rose with increasing gestational age in both cases and controls but remained significantly higher among those who were diagnosed with preeclampsia. Differences in levels of copeptin between cases and controls became more apparent closer to time of diagnosis. No significant associations were found for gestational hypertension without proteinuria, gestational diabetes mellitus, or preterm birth without preeclampsia. Copeptin levels are elevated in pregnant women before diagnosis of preeclampsia with elevation specific to this pregnancy complication rather than hypertension alone.
Novel High-Throughput In Vitro Model for Identifying Hemodynamic-Induced Inflammatory Mediators of Cerebral Aneurysm Formation
Authors: Nowicki Kamil W. , Hosaka Koji , He Yong , McFetridge Peter S. , Scott Edward W. , Hoh Brian L.
Published: September 2014

Cerebral aneurysms are thought to develop at locations of hemodynamic shear stress, via an inflammatory process. The molecular mechanism that links shear stress to inflammation, however, is not completely understood. Progress in studying this disease is limited by a lack of a suitable in vitro model. To address this, we designed novel in vitro parallel-plate flow chamber models of a straight artery, a bifurcation, and a bifurcation aneurysm. We compared endothelial cell phenotypes across the 3 different models and among microenvironments within each flow model by cytokine array, ELISA, and relative immunofluorescence. Human aneurysms express interleukin-8 and chemokine (C-X-C motif) ligand 1 (CXCL1), whereas normal arteries do not. The bifurcation aneurysm model showed significantly higher interleukin-8 and CXCL1 levels than both the straight artery and bifurcation models. Within the bifurcation and bifurcation aneurysm models, endothelial cells near the bifurcation or within the aneurysm sac microenvironments have significantly higher expression of CXCL1, and interleukin-8 and CXCL1, respectively, than at the straight proximal segment or the limbs of the bifurcation. Murine aneurysms express CXCL1, and it is the primary ELR
+
CXC chemokine expressed, whereas normal arteries do not. CXCL1 antibody blockade results in significantly fewer murine aneurysms (13.3 versus 66.7%;
P
=0.0078), decreased neutrophil infiltration, and vascular cell adhesion molecule 1 expression than an immunoglobulin G control. We successfully designed and validated a novel hemodynamic model of cerebral aneurysms in vitro. We also show that shear stress–induced CXCL1 plays a critical role in cerebral aneurysm formation.
Seeing the Invisible: Maya Deren's Experiments in Cinematic Trance
Authors: Mollona Massimiliano
Published: September 2014

In July 1791, the story goes, a small voodoo gathering in Santo Domingo sparked the Haitian Revolution, the first black anti-colonial revolution in history. The glorious history of the “Republic of the black Jacobins” was often celebrated by Surrealist artists in New York and Paris in their exposé of the decadent state of colonial powers in the aftermath of the Second World War. For instance, Haiti is central to André Breton's anti-colonial manifesto, Aimé Cesaire's idea of negritude, Rudy Burckhardt's lyric film symphonies, and Zora Neale Hurston's novels on creole culture. In New York, negritude did not have quite the same revolutionary appeal as in Paris, where Josephine Baker was hailed as a Surrealist goddess of “natural” beauty and power. But the electric Haitian voodoo performances of dancer and choreographer Katherine Dunham attracted a diverse community of African-American artists, émigrés, intellectuals, and communist sympathizers in the off-limits clubs, cafés, and private parties in Harlem. In its uncontainable, carnivalesque power, open forms, and sexual energy, Haitian voodoo captured an attraction to the “primitive” that affected American intellectuals and popular culture alike. Before becoming a Hollywood star, Dunham, of mixed West African and Native American roots, traveled to Haiti to study voodoo rituals for an anthropology degree at the University of Chicago. Fusing American dance, European ballet, and voodoo movements, she became a symbol of the black diaspora. In a recent film interview, Dunham recalls how her young assistant (or “girl Friday,” in the parlance of the time) Maya Deren was fascinated by Haitian dance and would use it to steal the show in rehearsals, public performances, and glitzy parties. The daughter of Russian Jewish émigrés and Trotskyite activists, Deren was struck by the power of this syncretic dance, which blended different cultural backgrounds and formed political consciousnesses while always providing entertainment and energizing dinner parties and giving voice to invisible deities. In her experimental filmmaking, Deren infused this magnetic power of dance into cinema.
The Cat and the Owl: Remembering Chris Marker
Authors: Chan Paul
Published: September 2014

In October 2010, I emailed Chris to ask if he was interested in taking part in a special issue of E-flux Journal that art critic Sven Lütticken and I were editing. The issue focused on whether contemporary art had addressed the rise of right-wing populism in Europe, the US, and elsewhere, and how these largely nationalistic, homophobic, and xenophobic movements impacted culture and art. With the ascendance of the Tea Party, Sven and I wondered if it were possible to chart a genealogy of right-wing groups on both sides of the Atlantic and illuminate their familial relations.
Remembering Michael Asher at the Art Institute of Chicago, 1982
Authors: Rorimer Anne
Published: September 2014

The groundbreaking career of Michael Asher, in all of its visual and conceptual diversity, following his death in October 2012, will have to be studied and remembered henceforth by means of published and unpublished documentation. Permanent works by Asher are few, and the installations he realized over a period of more than four decades were, with the occasional fortuitous exception, mainly conceived for temporary exhibitions. In all practicality and in light of ever-shifting institutional circumstances, it is difficult to foresee any re-creation of these exhibitions. Because of each work's attention to and interconnection with the specific circumstances of its site at any one time, the reconstruction of an exhibition remains unlikely.
Feminine Orientalism or Modern Enchantment? Peiping and the Graphic Artists Elizabeth Keith and Bertha Lum, 1920s–1930s
Authors: Claypool Lisa
Published: September 2014

The ideological suppositions, images, and fantasy associated with orientalism has given rise to the conceptualization of a materialist “feminine orientalism.” The term refers to an historical moment in the early twentieth century when white women in Europe and North America defined their social roles and gender by appropriating male orientalist politics and ideology. This article challenges the concept of “feminine orientalism” through the study of the prints and travel writing of two modern graphic artists who sojourned in Republican-era Peiping in the 1920s and 1930s: Bertha Lum and Elizabeth Keith. Through close formal analysis of the new visions of Peiping that the two women conjured in their prints – a vision that relied as heavily on urban ethnography as it did on fantasy – it proposes an alternative concept of “modern enchantment” as a heuristic device to interpret gender. Drawing from Wolfgang Iser’s notions of the “fictive,” “modern enchantment” lays as much weight on Weberian modern rationality as it does on imagination, and critically functions as a means to recuperate cultural boundary crossing in female gender performance and construction.
The Politics of Religious Repetition
Authors: Miller Daniel
Published: September 2014

Otherwise diverse genealogical critiques of the discursive category “religion” share a concern to highlight the complicity of this category in colonial and neo-imperial projects, which are effected through the depoliticizing of non-Western subject populations. I argue that countering such depoliticization is more difficult than it may appear, and that some such critiques fall into a form of transcendental historicism that, in fact, further depoliticizes the subjects of colonialism and neo-imperialism. I develop this point through a specific consideration of two such studies, suggesting that their failure owes to their adoption of a mimetic understanding of cultural identity. As an alternative, I theorize the global “resurgence of religion” in terms of Jacques Derrida’s notion of “religion without religion,” arguing that such phenomena represent non-identical, as opposed to mimetic, repetitions of religion which disrupt colonial and neo-imperial legacies. This alternative theorization overcomes the depoliticization inherent in genealogically historicist approaches.
Sub-Seabed Storage in the Maritime Zones of the 1982 Law of the Sea Convention: Equitability over Sovereignty?
Authors: Lassen Merle
Published: September 2014

The ocean makes up most of our planet and plays a crucial role in the global climate system. Interfering with this sensitive system is thus very dangerous. At the same time, it is urgent to address climate change. Could sub-seabed storage be the salvation? It is a controversial topic that entails several legal as well as practical issues. At issue from a legal perspective is especially the question whether and in which parts of the ocean states would be allowed to store co2 under the un Convention on the Law of the Sea. Of crucial importance is the question whether sub-seabed storage qualifies as the exploitation of natural resources, because coastal states enjoy certain sovereign rights for these activities. From a practical point of view, the limited experience with sub-seabed storage is particularly challenging. It is impossible to foresee the effects this technique will have on the marine environment, the global climate, and future generations.
The Rights of States over Low-tide Elevations: A Legal Analysis
Authors: Lavalle Roberto
Published: September 2014

The United Nations Convention on the Law of the Sea takes low-tide elevations into account only by endowing them with the capacity to generate specific maritime areas, by themselves, whenever they lie within territorial seas, and, subject to certain conditions, when they are part of straight baselines. But it passes over in silence the question whether and what rights states have over these maritime features. In a 2001 judgment, the International Court of Justice has held that in general low-tide elevations are under the sovereignty of the coastal states if they lie within their territorial seas, while, in a 2012 judgment, it has held that low-tide elevations cannot be appropriated, which seems to leave those features out of the ken of the law if they are located in exclusive economic zones. But, strictly speaking, in expressing such views, the Court cannot be deemed to have laid down customary law. It seems, however, that compelling reasons can be found, some of which are derived from the above-mentioned Convention, for considering that, except for low-tide elevations located on the high seas, states have certain rights over all low-tide elevations.
The Domino Logic of the Darkest Moment
Authors: Ngoei Wen-Qing
Published: September 2014

This essay argues that Anglo-American memories of Japan’s victory in Singapore in 1942, which British Prime Minister Winston Churchill labeled Britain’s “darkest moment” in World War II, soon would underpin the domino logic within u.s. Cold War strategy. For both American and British policymakers, Japan’s war machine had fused together in interconnected insecurity the bastions of Euro-American colonial power. In Southeast Asia, it had imposed the condition that one state’s vulnerabilities impinged upon the stability of its neighbor. This vision of Southeast Asia’s interconnected insecurity was central to the domino logic within u.s. Cold War policy. u.s. policymakers’ preoccupation with containing communism in Vietnam arose significantly from how Japan had torn into Southeast Asia from Indochina. After World War II, u.s. and British policymakers perceived Southeast Asian insecurity through both the prism of Japanese imperialism and their fears of an older “Yellow Peril"—China and Southeast Asia’s Chinese diaspora. Indeed, u.s. and British officials anticipated, as well as echoed and confirmed, each other’s suspicions that China and its diaspora would collaborate to reprise Japan’s campaign.
Economic Superpower in an Age of Limits
Authors: Takeda Yu
Published: September 2014

This paper examines macroeconomic policy coordination between Japan and the United States under the locomotive strategy from 1977 to 1979. Previous studies have described the strategy as a fiasco because of its negative economic impact. In fact, the Japanese government, after two years of stimulus packages, quit trying to be a locomotive bringing other developed countries out of their economic difficulties and the u.s. government admitted it in 1979. On the other hand, as this article shows, bilateral cooperation with the United States under this strategy expanded the roles and burdens of Japan, an emerging economic superpower, in international economic policy coordination. Japan’s efforts to implement the strategy made the u.s. government believe that Tokyo would continue to respond to its request to bear larger international responsibilities, while it also increased awareness of Japan’s global role in Tokyo. These bilateral perceptual changes paved the way for subsequent policy coordination and Japan’s assumption of greater burdens, notably the adoption of large-scale stimulus packages under belt-tightening budgets.
Revision on genus Xizicus Gorochov (Orthoptera, Tettigoniidae, Meconematinae, Meconematini) with description of three new species form China
Authors: WANG HANQIANG , JING JUN , LIU XIANWEI , LI KAI
Published: September 2014

This work presents a revision of genus Xizicus, two new subgenera are described: Xizicus (Zangxizicus) subgen. nov. and Xizicus (Haploxizicus) subgen. nov. Three new species are described, namely Xizicus (Paraxizicus) fallax sp. nov., Xizicus (Zangxizicus) tibeticus sp. nov. and Xizicus (Zangxizicus) quadrifascipes sp. nov.. Keys to subgenera and species are provided.
Three new polar species of Sternaspis Otto, 1821 (Polychaeta: Sternaspidae)
Authors: SALAZAR-VALLEJO SERGIO I.
Published: September 2014

Two sternaspid species, Sternaspis fossor Stimpson, 1853 and S. scutata (Ranzani, 1817), have been recorded from many localities including polar or subpolar environments. The study of the collections of five major institutions cannot confirm their presence in high latitudes. On the contrary, the specimens are regarded as different, undescribed species, and are herein described as one from Arctic environments, S. buzhinskajae n. sp., and two others from Antarctic localities: S. monroi n. sp., and S. sendalli n. sp. A key to identify all Sternaspis species is included.
New records and a new species of the cavernicolous genus Guiodytes Tian, 2013 from Guangxi, China (Coleoptera: Carabidae: Scaritinae)
Authors: TIAN MINGYI
Published: September 2014

A new species of the genus Guiodytes Tian, 2013 is described from a limestone cave called Shuiku Dong in Huanjiang County of northernmost Guangxi, southern China. G. deharvengi n. sp. is the first depigmented species of Guiodytes. It is close to G. cavicola Tian, 2013, but easily recognized by its broader and yellowish brown body. In addition, new records for G. cavicola Tian, 2013 are provided from two caves in Du’an County of northern Guangxi, with description of the male genitalia. A key to all three known species and a distributional map of Guiodytes are also given.
Brutalization Revisited: The Case of Russia
Authors: Beyrau Dietrich
Published: September 2014

In the case of Russia, the existence of a relationship between lost war, revolution, and Civil War is obvious. Unlike the German case, however, it has not been investigated in any detail. The Great War is often seen as the ‘forgotten war’ in the shadow of the Revolution of 1917 and the Civil War of 1918–21. Inspired by George Mosse’s work on Germany, this article investigates the connections between these conflicts. It argues that it is not easy to reconstruct the direct linkages between the fronts of an industrialized war to the violence of revolution and civil war. Rather, enduring traditions were transferred, transformed, and radicalized: the style of rule, the result of an absent political and patriotic consensus between the heterogeneous communities of communication, and dispositions to violence among the decisive sectors of the population, not only the soldiers and the revolutionaries, but also the peasants and workers longing for an egalitarian and just economy. The main role of the war was that it destroyed the old state and set these pre-existing violent tendencies free, which began to feed on themselves.
Application of Construal-Level Theory to Promotional Strategies in the Hotel Industry
Authors: Kim Jungkeun , Kim Peter BeomCheol , Kim Jae-Eun , Magnini Vincent P.
Published: September 2014

Effectively promoting products and services is important for the success of tourism companies in the competitive business environment. Based on construal level theory, this study examines whether psychological distance (temporal and spatial) influences preferred promotional messages in the tourism industry. The results from three experimental studies indicate that people who plan a vacation in the distant-future/to a far-destination prefer abstract promotional messages, while those who plan in the near-future/to a near-destination prefer concrete ones. We also find that informational media (textual vs. pictorial) have significant influences regarding the impact of psychological distance on travelers’ preferred promotional information. Further, using a field study, we investigate whether the current advertisements produced by tourism organizations are properly designed to be congruent with spatially driven construal levels (e.g., concrete promotional information for a near destination) but find them incongruent with what this study suggests. Implications of the findings are discussed for both researchers and practitioners.