bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Electronic Messaging on Physical Activity Participation among Older Adults
Authors: Antoine Parker Chantrell , Ellis Rebecca
Published: May 2016

The purpose of this study was to determine if electronic messaging would increase min of aerobic physical activity (PA) among older adults. Participants were active older adults (n=28; M age = 60 years, SD = 5.99, and range = 51–74 years). Using an incomplete within-subjects crossover design, participants were randomly assigned to begin the 4-week study receiving the treatment condition (a morning and evening text message) or the control condition (an evening text message). Participants self-reported min of completed aerobic PA by cell phone text. The 1-way within-subjects ANOVA showed significant group differences (p<0.05). Specifically, when participants were in the treatment condition, they reported significantly greater average weekly min of aerobic PA (M = 96.88 min, SD = 62.9) compared to when they completed the control condition (M = 71.68 min, SD = 40.98). Electronic messaging delivered via cell phones was effective at increasing min of aerobic PA among older adults.
Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats
Authors: Afroz Rizwana , Tanvir E. M. , Karim Nurul , Hossain Md. Sabir , Alam Nadia , Gan Siew Hua , Khalil Md. Ibrahim
Published: May 2016

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.
Human Action Recognition Using Improved Salient Dense Trajectories
Authors: Li Qingwu , Cheng Haisu , Zhou Yan , Huo Guanying
Published: May 2016

Human action recognition in videos is a topic of active research in computer vision. Dense trajectory (DT) features were shown to be efficient for representing videos in state-of-the-art approaches. In this paper, we present a more effective approach of video representation using improved salient dense trajectories: first, detecting the motion salient region and extracting the dense trajectories by tracking interest points in each spatial scale separately and then refining the dense trajectories via the analysis of the motion saliency. Then, we compute several descriptors (i.e., trajectory displacement, HOG, HOF, and MBH) in the spatiotemporal volume aligned with the trajectories. Finally, in order to represent the videos better, we optimize the framework of bag-of-words according to the motion salient intensity distribution and the idea of sparse coefficient reconstruction. Our architecture is trained and evaluated on the four standard video actions datasets of KTH, UCF sports, HMDB51, and UCF50, and the experimental results show that our approach performs competitively comparing with the state-of-the-art results.
A Heuristic Task Scheduling Algorithm for Heterogeneous Virtual Clusters
Authors: Lin Weiwei , Wu Wentai , Wang James Z.
Published: May 2016

Cloud computing provides on-demand computing and storage services with high performance and high scalability. However, the rising energy consumption of cloud data centers has become a prominent problem. In this paper, we first introduce an energy-aware framework for task scheduling in virtual clusters. The framework consists of a task resource requirements prediction module, an energy estimate module, and a scheduler with a task buffer. Secondly, based on this framework, we propose a virtual machine power efficiency-aware greedy scheduling algorithm (VPEGS). As a heuristic algorithm, VPEGS estimates task energy by considering factors including task resource demands, VM power efficiency, and server workload before scheduling tasks in a greedy manner. We simulated a heterogeneous VM cluster and conducted experiment to evaluate the effectiveness of VPEGS. Simulation results show that VPEGS effectively reduced total energy consumption by more than 20% without producing large scheduling overheads. With the similar heuristic ideology, it outperformed Min-Min and RASA with respect to energy saving by about 29% and 28%, respectively.
Parkinson’s Disease: The Mitochondria-Iron Link
Authors: Muñoz Yorka , Carrasco Carlos M. , Campos Joaquín D. , Aguirre Pabla , Núñez Marco T.
Published: May 2016

Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson’s disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences—mitochondrial dysfunction, iron accumulation, and oxidative damage—generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson’s disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation—by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways—is a viable therapy for retarding this cycle.
Effects of Nutrients in Substrates of Different Grains on Aflatoxin B1Production byAspergillus flavus
Authors: Liu Jie , Sun Lvhui , Zhang Niya , Zhang Jiacai , Guo Jiao , Li Chong , Rajput Shahid Ali , Qi Desheng
Published: May 2016

The current study was to better understand the potential factors affecting aflatoxin B1(AFB1) accumulation varies between different grains. The nutrient composition and contents of defatted substrates were determined; additionally, according to the nutrient content of the substrates, the effects of starch, soluble sugars, amino acids, and trace elements on AFB1production and mycelial growth in Czapek-Dox medium were examined. These results verified that removal of lipids from ground substrates significantly reduced the substrate’s potential for AFB1production byAspergillus flavus. Maltose, glucose, sucrose, arginine, glutamic acid, aspartic acid, and zinc significantly induced AFB1production up to 1.7- to 26.6-fold. And stachyose more significantly promotedA. flavusgrowth than the other nutrients. Thus, this study demonstrated that, combined with the nutrients content of grains, in addition to lipids, sucrose, stachyose, glutamic acid, and zinc might play key roles in various grains that are differentially infected byA. flavus. Particularly, two new nutrients (arginine and stachyose) of the grains we found significantly stimulate AFB1production andA. flavusgrowth, respectively. The results provide new concepts for antifungal methods to protect food and animal feed from AFB1contamination.
Existence of Positive Solutions for Two-Point Boundary Value Problems of Nonlinear Finite Discrete Fractional Differential Equations and Its Application
Authors: Guo Caixia , Guo Jianmin , Gao Ying , Kang Shugui
Published: May 2016

This paper is concerned with the two-point boundary value problems of nonlinear finite discrete fractional differential equations. On one hand, we discuss some new properties of the Green function. On the other hand, by using the main properties of Green function and the Krasnoselskii fixed point theorem on cones, some sufficient conditions for the existence of at least one or two positive solutions for the boundary value problem are established.
3D Plasmonic Ensembles of Graphene Oxide and Nobel Metal Nanoparticles with Ultrahigh SERS Activity and Sensitivity
Authors: Lin Jing , Wang Xiansong , Shen Guangxia , Cui Daxiang
Published: May 2016

We describe a comparison study on 3D ensembles of graphene oxide (GO) and metal nanoparticles (silver nanoparticles (AgNPs), gold nanoparticles (GNPs), and gold nanorods (GNRs)) for surface-enhanced Raman scattering (SERS) application. For the first time, GNRs were successfully assembled on the surfaces of GO by means of electrostatic interactions without adding any surfactant. The SERS properties of GO/AgNPs, GO/GNPs, and GO/GNRs were compared using 2-mercaptopyridine (2-Mpy) as probing molecule. We found that GO/AgNPs and GO/GNPs substrates are not suitable for detecting 2-Mpy due to the very strongπ-πstacking interaction between the 2-Mpy molecules andsp2carbon structure of GO. Conversely, the GO/GNRs substrates show ultrahigh SERS activity and sensitivity of 2-Mpy with the detection limit as low as ~10-15 M, which is ~2-3 orders of magnitude higher than that of the corresponding GNRs.
Topiramate-Induced Persistent Eyelid Myokymia
Authors: Khalkhali Mohammadrasoul
Published: May 2016

Background. Topiramate (TPM) is a psychotropic drug, which is used mainly as an antiepileptic drug and now over the years is used for a wider range of indications, including migraine prophylaxis and binge eating disorders. Although ocular side effects of Topiramate have been frequently reported, neuroophthalmologic manifestations such as myokymia are rarely reported.Case Presentation. This case report presents a case of a 47-year-old woman who had begun TPM for binge eating problem. She developed unilateral long standing lower eyelid twitching, which progressed to upper eyelid and eyebrow at the same side. The patient was not a smoker or excessive alcohol or caffeine abuser. Increasing the resting time and changing life style made no significant changes in her eyelid twitching. There was no definite evidence by neuroimaging and clinical or laboratory evaluations causing eyelid myokymia. The symptoms resolved with discontinuation of TPM.Conclusion. Although eyelid myokymia is a benign and self-limited condition, it sometimes becomes a source of distress in chronic long standing cases. Physicians should be aware of the neuroophthalmologic side effects of this drug.
Collaborative Production Structure of Knowledge Sharing Behavior in Internet Communities
Authors: Wang Jiangtao , Yang Jian-mei , Chen Quan , Tsai Sang-Bing
Published: May 2016

Peer production has received considerable attention because it is a new mode of providing information. Online encyclopedias are one typical application of peer production. They allow anyone to freely create and share knowledge. Large numbers of volunteers participate and form various relationships in the process of creating and sharing knowledge. A heterogeneous network model is presented to analyze the collaborative relationship of sharing behavior, and a new network measurement is presented to investigate the network structure by mapping it into a quantum system. The results of the present work show that volunteers in online communities are heterogeneous and that the collective states induced by these collaborative production network structures are different at different times. Some collective states are ordered states while others are softly chaotic. Analysis of these collective states may provide completely different insight from the individual dynamic state of contributors in a network.
Failure Propagation Modeling and Analysis via System Interfaces
Authors: Zhao Lin , Thulasiraman Krishnaiyan , Ge Xiaocheng , Niu Ru
Published: May 2016

Safety-critical systems must be shown to be acceptably safe to deploy and use in their operational environment. One of the key concerns of developing safety-critical systems is to understand how the system behaves in the presence of failures, regardless of whether that failure is triggered by the external environment or caused by internal errors. Safety assessment at the early stages of system development involves analysis of potential failures and their consequences. Increasingly, for complex systems, model-based safety assessment is becoming more widely used. In this paper we propose an approach for safety analysis based on system interface models. By extending interaction models on the system interface level with failure modes as well as relevant portions of the physical system to be controlled, automated support could be provided for much of the failure analysis. We focus on fault modeling and on how to compute minimal cut sets. Particularly, we explore state space reconstruction strategy and bounded searching technique to reduce the number of states that need to be analyzed, which remarkably improves the efficiency of cut sets searching algorithm.
Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes
Authors: Silva Macedo Rodrigo , Peres Leal Mayara , Braga Tarcio Teodoro , Barioni Éric Diego , de Oliveira Duro Stephanie , Ratto Tempestini Horliana Anna Carolina , Câmara Niels Olsen Saraiva , Marcourakis Tânia , Farsky Sandra Helena Poliselli , Lino-dos-Santos-Franco Adriana
Published: May 2016

Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT) has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days) and treated or not with PBMT (1 and 5 h after each FA exposure). Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment.
Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets
Authors: Saulite Ieva , Hoetzenecker Wolfram , Weidinger Stephan , Cozzio Antonio , Guenova Emmanuella , Wehkamp Ulrike
Published: May 2016

Sézary syndrome (SS), an aggressive form of erythrodermic pruritic cutaneous T cell lymphoma (CTCL), from an immunological perspective characterized by increased Th2 cytokine levels, elevated serum IgE and impaired cellular immunity. Not only the clinical appearance but also the hallmark immunological characteristics of SS often share striking similarities with acute flares of atopic dermatitis (AD), a common benign chronic inflammatory skin disease. Given the overlap of several immunological features, the application of similar or even identical therapeutic approaches in certain stages of both diseases may come into consideration. The aim of this review is to compare currently accepted immunological aspects and possible therapeutic targets in AD and SS.
Toward Value-Based Pricing to Boost Cancer Research and Innovation
Authors: Ocana Alberto , Amir Eitan , Tannock Ian F.
Published: May 2016

The high market price of new anticancer agents has stimulated debate about the long-term sustainability of healthcare systems and whether these new agents can continue to be supported by public healthcare or by private insurers. In addition, some drugs have been approved with limited clinical benefit, raising concerns about setting a minimum requirement for medical benefit. Options to resolve these problems include raising the bar for approval of new drugs and/or pricing of new agents based on the medical benefit that they offer to patients. In this commentary, we suggest that new agents should be marketed in a two-step process that would include first the approval of the new drug by the regulatory agencies and second the introduction of a market price based on the medical benefit that the new intervention offers to patients. Introduction of value-based pricing would maintain the sustainability of health care systems and would improve drug development, as it would pressure pharmaceutical companies to become more innovative and avoid the development of compounds with limited benefit. Value-based pricing could also stimulate the funding of research directed to development of new anticancer drugs with novel mechanisms of action. Cancer Res; 76(11); 3127–9. ©2016 AACR.
Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy
Authors: Vacchelli Erika , Enot David P. , Pietrocola Federico , Zitvogel Laurence , Kroemer Guido
Published: May 2016

Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense double-stranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. Cancer Res; 76(11); 3122–6. ©2016 AACR.
Depletion of FOXM1 via MET Targeting Underlies Establishment of a DNA Damage–Induced Senescence Program in Gastric Cancer
Authors: Francica Paola , Nisa Lluís , Aebersold Daniel M. , Langer Rupert , Bladt Friedhelm , Blaukat Andree , Stroka Deborah , Martínez María Rodríguez , Zimmer Yitzhak , Medová Michaela
Published: May 2016

Purpose: Deregulated signaling via the MET receptor tyrosine kinase is abundant in gastric tumors, with up to 80% of cases displaying aberrant MET expression. A growing body of evidence suggests MET as a potential target for tumor radiosensitization.

Experimental Design: Cellular proliferation and DNA damage-induced senescence were studied in a panel of MET-overexpressing human gastric cancer cell lines as well as in xenograft models after MET inhibition and/or ionizing radiation. Pathways activation and protein expression were assessed by immunoblotting and immunohistochemistry. Tumor tissue microarrays (91 gastric cancer patients) were generated and copy number alteration (178 patients) and gene expression (373 patients) data available at The Cancer Genome Atlas were analyzed to assess the coalterations of MET and FOXM1.

Results: MET targeting administered before ionizing radiation instigates DNA damage–induced senescence (∼80%, P < 0.001) rather than cell death. MET inhibition–associated senescence is linked to the blockade of MAPK pathway, correlates with downregulation of FOXM1, and can be abrogated (11.8% vs. 95.3%, P < 0.001) by ectopic expression of FOXM1 in the corresponding gastric tumor cells. Cells with ectopic FOXM1 expression demonstrate considerable (∼20%, P < 0.001) growth advantage despite MET targeting, suggesting a novel clinically relevant resistance mechanism to MET inhibition as the copresence of both MET and FOXM1 protein (33%) and mRNA (30%) overexpression as well as gene amplification (24,7%) are common in patients with gastric cancer.

Conclusions: FOXM1, a negative regulator of senescence, has been identified as a key downstream effector and potential clinical biomarker that mediates MET signaling following infliction of DNA damage in gastric tumors. Clin Cancer Res; 22(21); 5322–36. ©2016 AACR.
Rectal Cancer: Assessment of Neoadjuvant Chemoradiation Outcome based on Radiomics of Multiparametric MRI
Authors: Nie Ke , Shi Liming , Chen Qin , Hu Xi , Jabbour Salma K. , Yue Ning , Niu Tianye , Sun Xiaonan
Published: May 2016

Purpose: To evaluate multiparametric MRI features in predicting pathologic response after preoperative chemoradiation therapy (CRT) for locally advanced rectal cancer (LARC).

Experimental Design: Forty-eight consecutive patients (January 2012–November 2014) receiving neoadjuvant CRT were enrolled. All underwent anatomical T1/T2, diffusion-weighted MRI (DWI) and dynamic contrast-enhanced (DCE) MRI before CRT. A total of 103 imaging features, analyzed using both volume-averaged and voxelized methods, were extracted for each patient. Univariate analyses were performed to evaluate the capability of each individual parameter in predicting pathologic complete response (pCR) or good response (GR) evaluated based on tumor regression grade. Artificial neural network with 4-fold validation technique was further utilized to select the best predictor sets to classify different response groups and the predictive performance was calculated using receiver operating characteristic (ROC) curves.

Results: The conventional volume-averaged analysis could provide an area under ROC curve (AUC) ranging from 0.54 to 0.73 in predicting pCR. While if the models were replaced by voxelized heterogeneity analysis, the prediction accuracy measured by AUC could be improved to 0.71–0.79. Similar results were found for GR prediction. In addition, each subcategory images could generate moderate power in predicting the response, which if combining all information together, the AUC could be further improved to 0.84 for pCR and 0.89 for GR prediction, respectively.

Conclusions: Through a systematic analysis of multiparametric MR imaging features, we are able to build models with improved predictive value over conventional imaging metrics. The results are encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailoring the treatment into the era of personalized medicine. Clin Cancer Res; 22(21); 5256–64. ©2016 AACR.
Antitumor Efficacy of Anti-GD2 IgG1 Is Enhanced by Fc Glyco-Engineering
Authors: Xu Hong , Guo Hongfen , Cheung Irene Y. , Cheung Nai-Kong V.
Published: May 2016

The affinity of therapeutic antibodies for Fcγ receptors (FcγRs) strongly influences their antitumor potency. To generate antibodies with optimal binding and immunologic efficacy, we compared the affinities of different versions of an IgG1 Fc region that had an altered peptide backbone, altered glycans, or both. To produce IgG1 with glycans that lacked α1,6-fucose, we used CHO cells that were deficient in the enzyme UDP-N-acetylglucosamine: α-3-d-mannoside-β-1,2-N-acetylglucosaminyltransferase I (GnT1), encoded by the MGAT1 gene. Mature N-linked glycans require this enzyme, and without it, CHO cells synthesize antibodies carrying only Man5-GlcNAc2, which were more effective in antibody-dependent cell-mediated cytotoxicity (ADCC). Our engineered IgG1, hu3F8-IgG1, is specific for GD2, a neuroendocrine tumor ganglioside. Its peptide mutant is IgG1-DEL (S239D/I332E/A330L), both produced in wild-type CHO cells. When produced in GnT1-deficient CHO cells, we refer to them as IgG1n and IgG1n-DEL, respectively. Affinities for human FcγRs were measured using Biacore T-100 (on CD16 and CD32 polymorphic alleles), their immunologic properties compared for ADCC and complement-mediated cytotoxicity (CMC) in vitro, and pharmacokinetics and antitumor effects were compared in vivo in humanized mice. IgG1n and IgG1n-DEL contained only mannose and acetylglucosamine and had preferential affinity for activating CD16s, over inhibitory CD32B, receptors. In vivo, the antitumor effects of IgG1, IgG1-DEL, and IgG1n-DEL were similar but modest, whereas IgG1n was significantly more effective (P < 0.05). Thus, IgG1n antibodies produced in GnT1-deficient CHO cells may have potential as improved anticancer therapeutics. Cancer Immunol Res; 4(7); 631–8. ©2016 AACR.
Chitinase 3 Like-1: An Emerging Molecule Involved in Diabetes and Diabetic Complications
Authors: Di Rosa Michelino , Malaguarnera Lucia
Published: May 2016

Chitinase 3 like-1 (CHI3L1) is a chitinase-like protein member of family 18 chitinases, expressed in innate immune cells and involved in endothelial dysfunction and tissue remodelling. Since CHI3L1 is highly expressed in a variety of inflammatory diseases of infectious and non-infectious aetiology, it is recognised as a non-invasive prognostic biomarker for inflammation. A variety of studies revealing the increase in CHI3L1 levels in obesity, insulin resistance and in pathological conditions, such as atherosclerosis, coronary artery disease, acute ischaemic stroke, nephropathy, diabetic retinopathy and osteolytic processes, have suggested that CHI3L1 may also play a critical role in the evolution and complication of diabetes mellitus (DM). In this review we highlight the impact of CHI3L1 expression in DM and its contribution to the complication of this disease.
Fibroblasts and Mesenchymal Stromal/Stem Cells Are Phenotypically Indistinguishable
Authors: Denu Ryan A. , Nemcek Steven , Bloom Debra D. , Goodrich A. Daisy , Kim Jaehyup , Mosher Deane F. , Hematti Peiman
Published: May 2016

Background/Aims: Human mesenchymal stromal/stem cells (MSCs), derived from many different tissues, are characterized by a fibroblast-like morphology, the expression of certain cell surface markers and their ability to differentiate into adipocytes, chondrocytes and osteoblasts. A number of studies have shown that MSCs share many characteristics with fibroblasts; however, there is no well-defined set of phenotypic characteristics that could distinguish between these 2 types of cells. Methods: We used 4 well-established human fibroblast strains from 3 different tissue sources and several human MSC strains from 2 different tissue sources to compare the phenotypic and immunological characteristics of these cells. Results: Fibroblast strains had a similar morphology to MSCs, expressed the same cell surface markers as MSCs and could also differentiate into adipocytes, chondrocytes and osteoblasts. Also, similar to MSCs, these fibroblasts were capable of suppressing T cell proliferation and modulating the immunophenotype of macrophages. We also show that MSCs deposit extracellular matrices of collagen type I and fibronectin, and express FSP1 in patterns similar to fibroblasts. Conclusions: Based on currently accepted definitions for cultured human MSCs and fibroblasts, we could not find any immunophenotypic property that could make a characteristic distinction between MSCs and fibroblasts.
MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb
Authors: Deng Peng , Chen Ling , Liu Zheng , Ye Ping , Wang Sihua , Wu Jie , Yao Yufeng , Sun Yuan , Huang Xiaofan , Ren Linyun , Zhang Anchen , Wang Ke , Wu Chuangyan , Yue Zhang , Xu Xuezeng , Chen Manhua
Published: May 2016

Background/Aims: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown. Methods: We used the transverse aortic constriction (TAC) mouse model to study the role of miR-150 in cardiac fibrosis induced by pressure overload. After the TAC operation, qRT-PCR was used to measure the expression profiles of miR-150 in left ventricle tissues and populations of primary heart cell types. Then, we used both miR-150 knockout mice and wild type (WT) mice in the TAC model. Changes in cardiac function and pathology were measured using transthoracic echocardiography and pathological analysis, respectively. Furthermore, we predicted the target of miR-150 in cardiac fibroblasts (CFs) and completed in vitro CF transfection experiments using miR-150 analogs and siRNA corresponding to the predicted target. Results: We observed decreased expression levels of miR-150 in hearts suffering pressure overload, and these levels decreased more sharply in CFs than in cardiomyocytes. In addition, the degrees of cardiac function deterioration and cardiac fibrosis in miR-150-/- mice were more severe than were those in WT mice. By transfecting CFs with an miR-150 analog in vitro, we observed that miR-150 inhibited cardiac fibroblast activation. We predicted that the transcription factor c-Myb was the target of miR-150 in CFs. Transfecting CFs with c-Myb siRNA eliminated the effects of an miR-150 inhibitor, which promoted CF activation. Conclusion: These findings reveal that miR-150 acts as a pivotal regulator of pressure overload-induced cardiac fibrosis by regulating c-Myb.
TNF-α Activates High-Mobility Group Box 1 - Toll-Like Receptor 4 Signaling Pathway in Human Aortic Endothelial Cells
Authors: Yang Won Seok , Han Nam Jeong , Kim Jin Ju , Lee Mee Jeong , Park Su-Kil
Published: May 2016

Background/Aims: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-α (TNF-α) signal transduction in human aortic endothelial cells. Methods: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. Results: TNF-α activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-α stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-α-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-α-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-α activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-α stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-α-induced Syk activation and ET-1 production. Conclusion: Upon TNF-α stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction.
IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions
Authors: Hu Xiaorong , Ma Ruisong , Lu Jiajia , Zhang Kai , Xu Weipan , Jiang Hong , Da Yurong
Published: May 2016

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.
Monitoring of Potential Safety Events and Vital Signs during Active Mobilization of Patients Undergoing Continuous Renal Replacement Therapy in a Medical Intensive Care Unit
Authors: Lee Hyun , Ko Young Jun , Jung Jinhee , Choi Aeng Ja , Suh Gee Young , Chung Chi Ryang
Published: May 2016

Background/Aims: This study aims to evaluate potential safety events and vital sign changes during active mobilization physical therapy (PT) in critically ill patients undergoing continuous renal replacement therapy (CRRT). Methods: A retrospective review was performed on 29 patients who were treated with CRRT and who underwent 81 PT sessions in a medical intensive care unit at a single referral hospital; 15 patients underwent 33 sessions with passive range of motion (PROM) and 17 patients underwent 48 active mobilization PT sessions. Three patients received both types of PT including 8 PROM and 5 active mobilization PT sessions. The occurrences of safety events and vital sign changes during active mobilization PT sessions were evaluated. Results: The safety events did not develop during 33 sessions with PROM. However, there were 2 safety events (4.1%) during 48 active mobilization PT sessions including one session with mobilization in the bed and the other in a sitting position on the edge of the bed. These safety events exclusively developed during active mobilization PT sessions, in which concomitant extracorporeal membrane oxygenation (ECMO) support and CRRT were delivered. Regarding vital sign changes during PT sessions, there were no significant differences in systolic blood pressure (BP), diastolic BP, mean arterial pressure, heart rate, respiratory rate, or peripheral oxygen saturation before and after both PROM and active mobilization PT sessions. Conclusions: This study showed that active mobilization PT can be performed safely in patients who are being treated with CRRT without a significant hemodynamic change. However, the development of potential safety events in patients with ECMO needs to be monitored carefully.
Multimodal Imaging of Choroidal Neovascularization Associated with Sclerochoroidal Calcification
Authors: Bessette Angela P. , Singh Arun D.
Published: May 2016

We report a case of a choroidal neovascular membrane (CNVM) associated with sclerochoroidal calcification (SCC). An asymptomatic, 72-year-old male was referred to our institution for yellow-white placoid retinal lesions of both eyes. B-scan ultrasonography confirmed the diagnosis of SCC, and indocyanine green angiography confirmed the presence of an associated CNVM. Due to enlargement of a hemorrhagic pigment epithelial detachment associated with the CNVM over the course of 7 months, the patient was treated with a series of bevacizumab injections followed by photodynamic therapy (PDT). Due to persistence of the CNVM following PDT, the lesion was finally treated with argon laser photocoagulation. We describe the clinical course of this rare complication of SCC.
Semi-Competing Risks Data Analysis
Authors: Haneuse Sebastien , Lee Kyu Ha
Published: May 2016

Hospital readmission is a key marker of quality of health care. Notwithstanding its widespread use, however, it remains controversial in part because statistical methods used to analyze readmission, primarily logistic regression and related models, may not appropriately account for patients who die before experiencing a readmission event within the time frame of interest. Toward resolving this, we describe and illustrate the semi-competing risks framework, which refers to the general setting where scientific interest lies with some nonterminal event (eg, readmission), the occurrence of which is subject to a terminal event (eg, death). Although several statistical analysis methods have been proposed for semi-competing risks data, we describe in detail the use of illness–death models primarily because of their relation to well-known methods for survival analysis and the availability of software. We also describe and consider in detail several existing approaches that could, in principle, be used to analyze semi-competing risks data, including composite end point and competing risks analyses. Throughout we illustrate the ideas and methods using data on N=49 763 Medicare beneficiaries hospitalized between 2011 and 2013 with a principle discharge diagnosis of heart failure.
Comparative Effectiveness of Carotid Artery Stenting Versus Carotid Endarterectomy Among Medicare Beneficiaries
Authors: Jalbert Jessica J. , Nguyen Louis L. , Gerhard-Herman Marie D. , Kumamaru Hiraku , Chen Chih-Ying , Williams Lauren A. , Liu Jun , Rothman Andrew T. , Jaff Michael R. , Seeger John D. , Benenati James F. , Schneider Peter A. , Aronow Herbert D. , Johnston Joseph A. , Brott Thomas G. , Tsai Thomas T. , White Christopher J. , Setoguchi Soko
Published: May 2016

Background—

Effectiveness of carotid artery stenting (CAS) relative to carotid endarterectomy (CEA) among Medicare patients has not been established. We compared effectiveness of CAS versus CEA among Medicare beneficiaries.

Methods and Results—

We linked Medicare data (2000–2009) to the Society for Vascular Surgery’s Vascular Registry (2005–2008) and the National Cardiovascular Data Registry's (NCDR) Carotid Artery Revascularization and Endarterectomy Registry (2006–2008/2009). Medicare patients were followed up from procedure date until death, stroke/transient ischemic attack, periprocedural myocardial infarction, or a composite end point for these outcomes. We derived high-dimensional propensity scores using registry and Medicare data to control for patient factors and adjusted for provider factors in a Cox regression model comparing CAS with CEA. Among 5254 Society for Vascular Surgery’s Vascular Registry (1999 CAS; 3255 CEA) and 4055 Carotid Artery Revascularization and Endarterectomy Registry (2824 CAS; 1231 CEA) Medicare patients, CAS patients had a higher comorbidity burden and were more likely to be at high surgical risk (Society for Vascular Surgery’s Vascular Registry: 96.7% versus 44.5%; Carotid Artery Revascularization and Endarterectomy Registry: 71.3% versus 44.7%). Unadjusted outcome risks were higher for CAS. Mortality risks remained elevated for CAS after adjusting for patient-level factors (hazard ratio, 1.24; 95% confidence interval, 1.06–1.46). After further adjustment for provider factors, differences between CAS and CEA were attenuated or no longer present (hazard ratio for mortality, 1.13; 95% confidence interval, 0.94–1.37). Performance was comparable across subgroups defined by sex and degree of carotid stenosis, but there was a nonsignificant trend suggesting a higher risk of adverse outcomes in older (>80) and symptomatic patients undergoing CAS.

Conclusions—

Outcomes after CAS and CEA among Medicare beneficiaries were comparable after adjusting for both patient- and provider-level factors.
Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice
Authors: Wu Chia-Hua , Mohammadmoradi Shayan , Thompson Joel , Su Wen , Gong Ming , Nguyen Genevieve , Yiannikouris Frédérique
Published: May 2016

Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR–deficient mice (
PRR

Adi/Y

) with almost no detectable white adipose tissues. As a consequence, the livers of
PRR

Adi/Y

mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR–deficient mice were resistant to diet-induced obesity. Both high-fat– and low-fat–fed
PRR

Adi/Y

mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat–fed
PRR

Adi/Y

mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in
PRR

Adi/Y

mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and
PRR

Adi/Y

mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation.
Guideline Recommended Medical Therapy for Cardiovascular Diseases in the Obese: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program
Authors: Valle Javier A. , O'Donnell Colin I. , Armstrong Ehrin J. , Bradley Steven M. , Maddox Thomas M. , Ho P. Michael
Published: May 2016

Background

Stigma against the obese is well described in health care and may contribute to disparities in medical decision‐making. It is unknown whether similar disparity exists for obese patients in cardiovascular care. We evaluated the association between body mass index (
BMI
) and prescription of guideline‐recommended medications in patients undergoing elective percutaneous coronary intervention.

Methods and Results

Using data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking System Program, we identified patients undergoing elective percutaneous coronary intervention from 2007 to 2012, stratifying them by category of
BMI
. We described rates of prescription for class I guideline recommended medications for each
BMI
category (normal, overweight, and obese). Multivariable logistic regression assessed the association between
BMI
category and medication prescription. Seventeen thousand thirty‐seven patients were identified, with 35.3% having overweight
BMI
, and 50.8% obese
BMI
. Obese patients were more likely than normal
BMI
patients to be prescribed β‐blockers (
OR
1.34), statins (
OR
1.39), or
ACE
/
ARB
(odds ratio [
OR
] 1.52; all significant) when indicated. Overweight patients were more likely than normal
BMI
patients to be prescribed statins (
OR
1.29) and angiotensin‐converting enzymes/angiotensin
II
receptor blockers (
OR
1.41) when indicated. There was no association between
BMI
category and prescription of anticoagulants.

Conclusions

Over 85% of patients undergoing elective percutaneous coronary intervention in the Veterans Affairs are overweight or obese. Rates of guideline‐indicated medication prescription were <70% among all patients, and across
BMI
categories, with an association between increased
BMI
and greater use of guideline‐recommended medications. Our findings offer a possible contribution to the obesity paradox seen in many cardiovascular conditions.
Zeus on the stud farm? Against a Homeric instance of attractio relativi
Authors: Probert Philomen
Published: May 2016

The genitive ἧς atIliad5.265 is sometimes considered due toattractio relativi. Alternatively it is taken as a partitive or ablatival genitive, or emended. The question matters for Greek linguistic chronology because uncontroversialattractio relativiis not found until the fifth century BC. This paper addresses the question via a fresh examination of the syntax and sense of lines 265-269. The linguistically most plausible views are: (i) we should not understand εἰσίν with τῆς γάρ τοι γενεῆς, nor punctuate strongly after 267; (ii) ἧς should stand, and is a partitive genitive; (iii) οὕνεκα means ‘because’. The resulting interpretation implies that Zeus accessed some pre-existing stock of horses, otherwise unknown to Greek literature. For many scholars this is a fatal objection to ἧς as a partitive genitive, with some concluding that ἧς is due toattractio relativior corrupt, and others that ἧς is an ‘ablatival genitive’ (a suggestion that does not solve the perceived problem). This paper defends the partitive genitive analysis on the grounds that Homeric audiences could easily have imagined Zeus getting the horses from some pre-existing stock. Parallels support the plausibility of this background assumption. We do not have a Homeric instance ofattractio relativi.
A review of genera and described Afrotropical species of Tetracampinae (Hymenoptera: Tetracampidae), with description of a new genus from East Central Africa
Authors: GUMOVSKY ALEX
Published: May 2016

The genera and described Afrotropical species of Tetracampinae Förster (Hymenoptera: Chalcidoidea, Tetracampidae) are reviewed. Despite the vague nature of some generic concepts, eight genera are recognized for the subfamily, i.e. Cassidocida Crawford, Diplesiostigma Girault, Dipriocampe Bouček, Epiclerus Haliday, Foersterella Dalla Torre, Niticampe Bouček, Tetracampe Förster, and the newly described Kilomotoia Gumovsky gen. n. The latter genus is established for Kilomotoia kitoko Gumovsky sp. n., collected from abandoned cultivated areas in the humid forest zone of North East Democratic Republic of Congo (Ituri forest, Ituri Province, environs of Mongbwalu village) and Central Uganda (Mabira forest, environs of Najembe village). Kilomotoia is distinguished from other tetracampine genera by the possession of a flattened dorsum, large abrupt pronotum, relatively long and laterally depressed gaster having gastral tergites II–V with medially emarginate posterior margins, and the hypopygium extending to the apex of gaster as sharply pointed mucro. The four hitherto described Afrotropical tetracampine species are reviewed based on available museum material, with Cassidocida africana Ferrière transferred to Foersterella as F. africana (Ferrière) comb. n., E. agromyzae (Risbec) and E. plectroniae (Risbec) confirmed as species of Epiclerus (as transferred earlier from Foersterella by Bouček 1958 and Bouček & Askew 1968), and Cassidocida orthopterae Risbec transferred to Closterocerus (Eulophidae, Entedoninae) as C. orthopterae (Risbec) comb. n. New diagnostic characters are proposed for the subfamily and some genera, and a comparative character table provided for tetracampine genera.