BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Determination of Elemental Composition of Malabar spinach, Lettuce, Spinach, Hyacinth Bean, and Cauliflower Vegetables Using Proton Induced X-Ray Emission Technique at Savar Subdistrict in Bangladesh Thu, 02 Jul 2015 06:42:58 +0000 The concentrations of 18 different elements (K, Ca, Fe, Cl, P, Zn, S, Mn, Ti, Cr, Rb, Co, Br, Sr, Ru, Si, Ni, and Cu) were analyzed in five selected vegetables through Proton Induced X-ray Emission (PIXE) technique. The objective of this study was to provide updated information on concentrations of elements in vegetables available in the local markets at Savar subdistrict in Bangladesh. These elements were found in varying concentrations in the studied vegetables. The results also indicated that P, Cl, K, Ca, Mn, Fe, and Zn were found in all vegetables. Overall, K and Ca exhibited the highest concentrations. Cu and Ni exhibited the lowest concentrations in vegetables. The necessity of these elements was also evaluated, based on the established limits of regulatory standards. The findings of this study suggest that the consumption of these vegetables is not completely free of health risks. S. M. Fahad, A. F. M. Mahmudul Islam, Mahiuddin Ahmed, Nizam Uddin, Md. Rezaul Alam, Md. Ferdous Alam, Md. Farhan Khalik, Md. Sazzad Hossain, Md. Lokman Hossain, and Md. Joynal Abedin Copyright © 2015 S. M. Fahad et al. All rights reserved. RLN2 Is a Positive Regulator of AKT-2-Induced Gene Expression Required for Osteosarcoma Cells Invasion and Chemoresistance Thu, 02 Jul 2015 05:48:19 +0000 The aim of the study was to determine the effect of H2 relaxin (RLN2) on invasion, migration, and chemosensitivity to cisplatin in human osteosarcoma U2-OS and MG-63 cells and then to investigate the effect of RLN2 on the AKT/NF-κB signaling pathway. The expression of RLN2, p-AKT (Ser473), and p-ERK1/2 (Phospho-Thr202/Tyr204) proteins was detected by western blot in OS tissues from 21 patients with pulmonary metastatic disease, and the correlation between RLN2 and p-AKT or RLN2 and p-ERK1/2 expression was investigated. RLN2 expression was inhibited by RLN2 siRNA transfection in the MG-63 cells. RLN2 was overexpressed in the U2-OS cells by treatment with recombinant relaxin. The results showed that positive relation was found between RLN2 and p-AKT expression in tissues of OS. Silencing RLN2 inhibited cell migratory and invasive ability and angiogenesis formation and increased the chemosensitivity to cisplatin in MG-63 cells. RLN2 overexpression promoted migratory and invasive ability and angiogenesis and increased the chemoresistance to cisplatin in U2-OS cells. Silencing RLN2 inhibited the activity of AKT/NF-κB signaling pathway in MG-63 cells, and vice versa. Blockage of both pathways by specific inhibitors abrogated RLN2-induced survival and invasion of OS cells, and vice versa. Our results indicated RLN2 confers to migratory and invasive ability, angiogenesis, and chemoresistance to cisplatin via modulating the AKT/NF-κB signaling pathway in vitro. Jinfeng Ma, Hai Huang, Zenggang Han, Changzheng Zhu, and Bin Yue Copyright © 2015 Jinfeng Ma et al. All rights reserved. An Integrated Approach Using Spatial Analysis to Study the Risk Factors for Leishmaniasis in Area of Recent Transmission Wed, 01 Jul 2015 12:07:00 +0000 Some epidemiological aspects of leishmaniasis in the municipality of Formiga, Brazil, an important touristic site, were evaluated. Those included phlebotomine sand fly vectors, canine infection, and geoprocessing analysis for determining critical transmission areas. Sand flies (224 insects) belonging to ten different species were captured. The most captured species included Lutzomyia longipalpis (35.3%), Lutzomyia cortelezzii (33.5%), and Lutzomyia whitmani (18.3%). A significant correlation between sand fly densities and climatic conditions was detected. Serological diagnosis (DPP and ELISA) was performed in 570 dogs indicating a prevalence of 5.8%. After sequencing the main species circulating in the area were Leishmania infantum and Leishmania braziliensis. Spatial analysis demonstrated that vegetation and hydrography may be related to sand fly distribution and infected dogs. The municipality of Formiga has proven leishmaniasis vectors and infected dogs indicating the circulation of the parasite in the city. Correlation of those data with environmental and human cases has identified the critical areas for control interventions (south, northeast, and northwest). In conclusion, there is current transmission of visceral and canine human cases and the city is on the risk for the appearance of cutaneous cases. Júlia Alves Menezes, Eduardo de Castro Ferreira, José Dilermando Andrade-Filho, Alessandra Mara de Sousa, Mayron Henrique Gomes Morais, Ana Maria Sampaio Rocha, George Luis Lins Machado-Coelho, Fernanda Pinheiro Lima, Ana Paula Madureira, Tânia Cristina Garcia, Christian Resende Freitas, Rodrigo Pedro Soares, and Carina Margonari Copyright © 2015 Júlia Alves Menezes et al. All rights reserved. Cyclic Tensile Strain Induces Tenogenic Differentiation of Tendon-Derived Stem Cells in Bioreactor Culture Wed, 01 Jul 2015 10:54:40 +0000 Different loading regimens of cyclic tensile strain impose different effects on cell proliferation and tenogenic differentiation of TDSCs in three-dimensional (3D) culture in vitro, which has been little reported in previous literatures. In this study we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation in the custom-designed 3D tensile bioreactor, which revealed that cyclic tensile strain with different frequencies (0.3 Hz, 0.5 Hz, and 1.0 Hz) and amplitudes (2%, 4%, and 8%) had no influence on TDSC viability, while it had different effects on the proliferation and the expression of type I collagen, tenascin-C, tenomodulin, and scleraxis of TDSCs, which was most obvious at 0.5 Hz frequency with the same amplitude and at 4% amplitude with the same frequency. Moreover, signaling pathway from microarray analysis revealed that reduced extracellular matrix (ECM) receptor interaction signaling initiated the tendon genius switch. Cyclic tensile strain highly upregulated genes encoding regulators of NPM1 and COPS5 transcriptional activities as well as MYC related transcriptional factors, which contributed to cell proliferation and differentiation. In particular, the transcriptome analysis provided certain new insights on the molecular and signaling networks for TDSCs loaded in these conditions. Yuan Xu, Qiang Wang, Yudong Li, Yibo Gan, Pei Li, Songtao Li, Yue Zhou, and Qiang Zhou Copyright © 2015 Yuan Xu et al. All rights reserved. Prevalence and Diagnostic Approach to Sleep Apnea in Hemodialysis Patients: A Population Study Wed, 01 Jul 2015 10:02:36 +0000 Background. Previous observations found a high prevalence of obstructive sleep apnea (OSA) in the hemodialysis population, but the best diagnostic approach remains undefined. We assessed OSA prevalence and performance of available screening tools to propose a specific diagnostic algorithm. Methods. 104 patients from 6 Swiss hemodialysis centers underwent polygraphy and completed 3 OSA screening scores: STOP-BANG, Berlin’s Questionnaire, and Adjusted Neck Circumference. The OSA predictors were identified on a derivation population and used to develop the diagnostic algorithm, which was validated on an independent population. Results. We found 56% OSA prevalence (AHI ≥ 15/h), which was largely underdiagnosed. Screening scores showed poor performance for OSA screening (ROC areas 0.538 [SE 0.093] to 0.655 [SE 0.083]). Age, neck circumference, and time on renal replacement therapy were the best predictors of OSA and were used to develop a screening algorithm, with higher discriminatory performance than classical screening tools (ROC area 0.831 [0.066]). Conclusions. Our study confirms the high OSA prevalence and highlights the low diagnosis rate of this treatable cardiovascular risk factor in the hemodialysis population. Considering the poor performance of OSA screening tools, we propose and validate a specific algorithm to identify hemodialysis patients at risk for OSA for whom further sleep investigations should be considered. Valentina Forni Ogna, Adam Ogna, Menno Pruijm, Isabelle Bassi, Emilie Zuercher, Georges Halabi, Olivier Phan, Roberto Bullani, Daniel Teta, Thierry Gauthier, Anne Cherpillod, Claudine Mathieu, Alexandra Mihalache, Francoise Cornette, José Haba-Rubio, Michel Burnier, and Raphaël Heinzer Copyright © 2015 Valentina Forni Ogna et al. All rights reserved. Heartbeat Cycle Length Detection by a Ballistocardiographic Sensor in Atrial Fibrillation and Sinus Rhythm Wed, 01 Jul 2015 09:44:16 +0000 Background. Heart rate monitoring is especially interesting in patients with atrial fibrillation (AF) and is routinely performed by ECG. A ballistocardiography (BCG) foil is an unobtrusive sensor for mechanical vibrations. We tested the correlation of heartbeat cycle length detection by a novel algorithm for a BCG foil to an ECG in AF and sinus rhythm (SR). Methods. In 22 patients we obtained BCG and synchronized ECG recordings before and after cardioversion and examined the correlation between heartbeat characteristics. Results. We analyzed a total of 4317 heartbeats during AF and 2445 during SR with a correlation between ECG and BCG during AF of (95% CI 0.68–0.71, ) and (95% CI 0.73–0.77, ) during SR. By adding a quality index, artifacts could be reduced and the correlation increased for AF to 0.76 (95% CI 0.74–0.77, , ) and for SR to 0.85 (95% CI 0.83–0.86, , ). Conclusion. Heartbeat cycle length measurement by our novel algorithm for BCG foil is feasible during SR and AF, offering new possibilities of unobtrusive heart rate monitoring. This trial is registered with IRB registration number EK205/11. This trial is registered with clinical trials registration number NCT01779674. Matthias Daniel Zink, Christoph Brüser, Patrick Winnersbach, Andreas Napp, Steffen Leonhardt, Nikolaus Marx, Patrick Schauerte, and Karl Mischke Copyright © 2015 Matthias Daniel Zink et al. All rights reserved. Diagnosing Paroxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia? Wed, 01 Jul 2015 08:46:50 +0000 Atrial fibrillation (AF) is the commonest sustained arrhythmia globally and results in significantly increased morbidity and mortality including a fivefold risk of stroke. Paroxysmal atrial fibrillation (PAF) constitutes approximately half of all AF cases and is thought to represent an early stage of the disease. This intermittent form of atrial arrhythmia can be a challenge to identify and as a result many affected individuals are not prescribed appropriate antithrombotic therapy and hence are at risk of stroke and thromboembolism. Despite these adverse outcomes there have been relatively few diagnostic advances in the field since the introduction of the Holter monitor in 1949. This review aims to establish the available evidence for electrophysiological, molecular, and morphological biomarkers to improve the detection of PAF with reference to the underlying mechanisms for the condition. P. J. Howlett, F. S. Hatch, V. Alexeenko, R. I. Jabr, E. W. Leatham, and C. H. Fry Copyright © 2015 P. J. Howlett et al. All rights reserved. Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study Wed, 01 Jul 2015 07:34:00 +0000 Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation , which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in . Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies. Francesca Cacciani and Massimiliano Zaniboni Copyright © 2015 Francesca Cacciani and Massimiliano Zaniboni. All rights reserved. Atrial Fibrillation and Fibrosis: Beyond the Cardiomyocyte Centric View Wed, 01 Jul 2015 07:27:49 +0000 Atrial fibrillation (AF) associated with fibrosis is characterized by the appearance of interstitial myofibroblasts. These cells are responsible for the uncontrolled deposition of the extracellular matrix, which pathologically separate cardiomyocyte bundles. The enhanced fibrosis is thought to contribute to arrhythmias “indirectly” because a collagenous septum is a passive substrate for propagation, resulting in impulse conduction block and/or zigzag conduction. However, the emerging results demonstrate that myofibroblasts in vitro also promote arrhythmogenesis due to direct implications upon cardiomyocyte electrophysiology. This electrical interference may be considered beneficial as it resolves any conduction blocks; however, the passive properties of myofibroblasts might cause a delay in impulse propagation, thus promoting AF due to discontinuous slow conduction. Moreover, low-polarized myofibroblasts reduce, via cell-density dependence, the fast driving inward current for cardiac impulse conduction, therefore resulting in arrhythmogenic uniformly slow propagation. Critically, the subsequent reduction in cardiomyocytes resting membrane potential in vitro significantly increases the likelihood of ectopic activity. Myofibroblast densities and the degree of coupling at cellular border zones also impact upon this likelihood. By considering future in vivo studies, which identify myofibroblasts “per se” as a novel targets for cardiac arrhythmias, this review aims to describe the implications of noncardiomyocyte view in the context of AF. Michele Miragoli and Alexey V. Glukhov Copyright © 2015 Michele Miragoli and Alexey V. Glukhov. All rights reserved. Results from the Registry of Atrial Fibrillation (AFABE): Gap between Undiagnosed and Registered Atrial Fibrillation in Adults—Ineffectiveness of Oral Anticoagulation Treatment with VKA Wed, 01 Jul 2015 07:25:14 +0000 Objective. This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC) medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk. Method. A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were , HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores. Results. The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a score; a risk of bleeding in important subgroups using OAC without indication (37.50% score); the use of OAC with TTR < 60% (33.1%), of whom 47.6% had a HAS-BLED score ≥3. Thus, 35.4% of the expected AF prevalence achieved an optimal time in the therapeutic range. Conclusions. The expected AF prevalence was 10.9% ( 5267), but the registered prevalence was 7.5% ( 3638). Only 35.04% (CI = 95%, 33.7–36.3) of AF patients treated with vitamin K antagonists (VKAs) achieve the goal of TTR > 60%. Anna Panisello-Tafalla, Josep Lluís Clua-Espuny, Vicente F. Gil-Guillen, Antonia González-Henares, María Lluisa Queralt-Tomas, Carlos López-Pablo, Jorgina Lucas-Noll, Iñigo Lechuga-Duran, Rosa Ripolles-Vicente, Jesús Carot-Domenech, and Miquel Gallofré López Copyright © 2015 Anna Panisello-Tafalla et al. All rights reserved. Evaluation of Single-Impact-Induced Cartilage Degeneration by Optical Coherence Tomography Wed, 01 Jul 2015 07:04:04 +0000 Posttraumatic osteoarthritis constitutes a major cause of disability in our increasingly elderly population. Unfortunately, current imaging modalities are too insensitive to detect early degenerative changes of this disease. Optical coherence tomography (OCT) is a promising nondestructive imaging technique that allows surface and subsurface imaging of cartilage, at near-histological resolution, and is principally applicable in vivo during arthroscopy. Thirty-four macroscopically normal human cartilage-bone samples obtained from total joint replacements were subjected to standardized single impacts in vitro (range: 0.25 J to 0.98 J). 3D OCT measurements of impact area and adjacent tissue were performed prior to impaction, directly after impaction, and 1, 4, and 8 days later. OCT images were assessed qualitatively (DJD classification) and quantitatively using established parameters (OII, Optical Irregularity Index; OHI, Optical Homogeneity Index; OAI, Optical Attenuation Index) and compared to corresponding histological sections. While OAI and OHI scores were not significantly changed in response to low- or moderate-impact energies, high-impact energies significantly increased mean DJD grades (histology and OCT) and OII scores. In conclusion, OCT-based parameterization and quantification are able to reliably detect loss of cartilage surface integrity after high-energy traumatic insults and hold potential to be used for clinical screening of early osteoarthritis. Florence de Bont, Nicolai Brill, Robert Schmitt, Markus Tingart, Björn Rath, Thomas Pufe, Holger Jahr, and Sven Nebelung Copyright © 2015 Florence de Bont et al. All rights reserved. Clinical, Psychopathological, and Personality Characteristics Associated with ADHD among Individuals Seeking Treatment for Gambling Disorder Wed, 01 Jul 2015 06:34:44 +0000 Objectives. (1) To assess the current presence of ADHD symptoms among patients seeking treatment for gambling disorder; (2) to explore clinical and sociodemographic differences between patients who score high and low on the measure of ADHD symptoms; (3) to analyze whether the presence of ADHD symptoms is associated with more severe psychopathology and with specific personality traits; (4) to analyze the mediating role of ADHD symptoms in the relationship between novelty seeking and gambling severity. Method. A total of 354 consecutive patients were administered an extensive battery assessing gambling behavior, psychopathology, and personality traits. Results. Male and female gamblers did not differ significantly in their mean scores on the ADHD measure. However, younger participants aged 18–35 scored higher. Higher ADHD scores were also associated with greater severity of gambling disorder and more general psychopathology. Regarding personality traits, high persistence and self-directedness were negatively related to ADHD scores, while in women alone a positive correlation was found between ADHD scores and scores on harm avoidance and self-transcendence. Conclusion. The presence of ADHD symptoms in both male and female gambling disorder patients may act as an indicator of the severity of gambling, general psychopathology, and dysfunctional personality traits. N. Aymamí, S. Jiménez-Murcia, R. Granero, J. A. Ramos-Quiroga, F. Fernández-Aranda, L. Claes, A. Sauvaget, M. Grall-Bronnec, M. Gómez-Peña, L. G. Savvidou, A. B. Fagundo, A. del Pino-Gutierrez, L. Moragas, M. Casas, E. Penelo, and J. M. Menchón Copyright © 2015 N. Aymamí et al. All rights reserved. Atorvastatin Treatment for Atrial Fibrillation Reduces Serum High-Sensitivity C-Reactive Protein Levels Wed, 01 Jul 2015 06:32:08 +0000 We investigated whether serum hs-CRP levels predict the efficacy of atrial fibrillation (AF) treated with atorvastatin. Bibliographic databases were exhaustively searched for studies relevant to the research topic. Newcastle-Ottawa Scale (NOS) criteria, combined with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), were applied for study quality assessment. Our meta-analysis identified seven cohort studies (2006~2013), providing information on the change in serum hs-CRP levels in AF patients receiving atorvastatin therapy. After atorvastatin treatment, hs-CRP level in AF patients decreased significantly (SMD = 1.02, 95% CI: 0.58–1.47, ). Subgroup analysis by country and hs-CRP detection methods suggested a negative relationship between atorvastatin treatment and hs-CRP levels among Chinese AF patients (SMD = 1.34, 95% CI: 1.00–1.69, ) and by using ELISA method (SMD = 1.11, 95% CI: 0.51–1.71, ), but not among Turkish population and using INA method (all ). Egger’s test showed no publication bias (). hs-CRP was clearly lowered in AF patients treated with atorvastatin, which may be helpful in the choice of statin agents for AF treatment. However, longer follow-ups are necessary to assess the clinical value of lowering hs-CRP in the clinical setting of AF treatment outcomes. Fang-Cheng Su, Xi-Dong Li, Shao-Xia Sun, Ming-Yu Shi, Feng-Hua Xue, Shi-Chao Teng, Li Jiang, Jing Zhu, Feng Yin, and Hong-Yue Gu Copyright © 2015 Fang-Cheng Su et al. All rights reserved. Impact of Dabigatran versus Phenprocoumon on ADP Induced Platelet Aggregation in Patients with Atrial Fibrillation with or without Concomitant Clopidogrel Therapy (the Dabi-ADP-1 and Dabi-ADP-2 Trials) Wed, 01 Jul 2015 06:28:43 +0000 Background. A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel’s efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals. Methods. The “Dabi-ADP-1” and “Dabi-ADP-2” trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 () patients with clopidogrel therapy were excluded and in Dabi-ADP-2 () patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Results. There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650–983] AU × min versus phenprocoumon: 839 [666–1039] AU × min, and Dabi-ADP-2: 326 [268–462] versus 350 [214–535], ) or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Conclusion. Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy. Amadea M. Martischnig, Julinda Mehilli, Janina Pollak, Tobias Petzold, Anette K. Fiedler, Katharina Mayer, Stefanie Schulz-Schüpke, Dirk Sibbing, Steffen Massberg, Adnan Kastrati, and Nikolaus Sarafoff Copyright © 2015 Amadea M. Martischnig et al. All rights reserved. Surgical Treatment of Concomitant Atrial Fibrillation: Focus onto Atrial Contractility Wed, 01 Jul 2015 06:25:18 +0000 Background. Maze procedure aims at restoring sinus rhythm (SR) and atrial contractility (AC). This study evaluated multiple aspects of AC recovery and their relationship with SR regain after ablation. Methods. 122 mitral and fibrillating patients underwent radiofrequency Maze. Rhythm check and echocardiographic control of biatrial contractility were performed at 3, 6, 12, and 24 months postoperatively. A multivariate Cox analysis of risk factors for absence of AC recuperation was applied. Results. At 2-years follow-up, SR was achieved in 79% of patients. SR-AC coexistence increased from 76% until 98%, while biatrial contraction detection augmented from 84 to 98% at late stage. Shorter preoperative arrhythmia duration was the only common predictor of SR-AC restoring, while pulmonary artery pressure (PAP) negatively influenced AC recuperation. Early AC restoration favored future freedom from arrhythmia recurrence. Minor LA dimensions correlated with improved future A/E value and vice versa. Right atrial (RA) contractility restoring favored better left ventricular (LV) performance and volumes. Conclusions. SR and left AC are two interrelated Maze objectives. Factors associated with arrhythmia “chronic state” (PAP and arrhythmia duration) are negative predictors of procedural success. Our results suggest an association between postoperative LA dimensions and “kick” restoring and an influence of RA contraction onto LV function. Claudia Loardi, Francesco Alamanni, Claudia Galli, Moreno Naliato, Fabrizio Veglia, Marco Zanobini, and Mauro Pepi Copyright © 2015 Claudia Loardi et al. All rights reserved. Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies? Mon, 29 Jun 2015 12:42:11 +0000 Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets. Brian R. Weil and Cevher Ozcan Copyright © 2015 Brian R. Weil and Cevher Ozcan. All rights reserved. The Genetic Deletion of 6q21 and PRDM1 and Clinical Implications in Extranodal NK/T Cell Lymphoma, Nasal Type Mon, 29 Jun 2015 12:32:04 +0000 6q21 genetic deletion has been frequently detected in extranodal NK/T cell lymphoma, nasal type (EN-NK/T-NT), and PRDM1 is considered as candidate gene. However, direct detection of PRDM1 deletion has not been well documented. We investigated genetic alterations of 6q21 and PRDM1 in 43 cases of EN-NK/T-NT and cell lines by FISH. PRDM1 expression was evaluated by immunohistochemistry and Western blot. The correlation between genetic alteration and PRDM1 expression and the significance in clinic-pathologic were analyzed. Heterozygous deletion of 6q21 and/or PRDM1 was observed in 24 of 43 cases (55.81%) of EN-NK/T-NT including 16 cases (37.21%) for 6q21 deletion and 19 cases (44.19%) for PRDM1 deletion. Similarly, heterozygous codeletion of 6q21 and PRDM1 was identified in NK92 and NKL cells. The heterozygous deletion of 6q21 and/or PRDM1 was correlated with PRDM1 expression. However, genetic deletion of 6q21 and/or PRDM1 was not correlated with clinicopathological features of EN-NK/T-NT, while PRDM1 expression showed positive effect on the outcome of patients as those as disease site, B symptom, and clinical stage. Thus, heterozygous deletion of 6q21 and/or PRDM1 was frequently detected in EN-NK/T-NT and correlated with downregulation of PRDM1. But the prognostic role of genetic deletion needs to be further evaluated in larger cohort. Li Liang, Zhang Zhang, Ying Wang, Lin Nong, Yalin Zheng, Linlin Qu, Bo Zhang, and Ting Li Copyright © 2015 Li Liang et al. All rights reserved. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure Mon, 29 Jun 2015 11:52:38 +0000 Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed. Olivier Phan, Marc Maillard, Hartmut H. Malluche, Jean-Christophe Stehle, Felix Funk, and Michel Burnier Copyright © 2015 Olivier Phan et al. All rights reserved. β-Elemene Inhibits Cell Proliferation by Regulating the Expression and Activity of Topoisomerases I and IIα in Human Hepatocarcinoma HepG-2 Cells Mon, 29 Jun 2015 11:17:46 +0000 Objective. To investigate the effects of β-Elemene (β-ELE) on the proliferation, apoptosis, and topoisomerase I (TOPO I) and topoisomerase IIα (TOPO IIα) expression and activity of human hepatocarcinoma HepG-2 cells. Methods. After treatment with β-ELE, morphological alterations of HepG-2 cells were observed under an inverted microscope. Cell proliferation was assessed using an MTT assay, cell cycles were analyzed using flow cytometry, and apoptosis was detected by Annexin V/PI staining. The expression of TOPO I and TOPO IIα was analyzed by Western blot techniques, and their activity was measured using the TOPO I-mediated, supercoiled pBR322 DNA relaxation and TOPO IIα-mediated Kinetoplast DNA (kDNA) decatenation assays, respectively. Supercoiled pBR322 and kDNA were also used to determine the direct effect of β-ELE on DNA breaks. Results. β-ELE significantly inhibited HepG-2 cell proliferation in a dose- and time-dependent manner. β-ELE also induced tumor cell arrest at S phase, induced cell apoptosis, and downregulated the protein expression of TOPO I and TOPO IIα in a dose-dependent manner. β-ELE also inhibited TOPO I- and TOPO IIα-mediated DNA relaxation but did not directly induce DNA breakage at any concentration. Conclusion. β-ELE could inhibit the proliferation of HepG-2 cells and interfere with the expression and activity of TOPO I and TOPO IIα. Min Gong, Ying Liu, Jian Zhang, Ya-jie Gao, Ping-ping Zhai, Xi Su, Xiang Li, Yan Li, Li Hou, and Xiao-nan Cui Copyright © 2015 Min Gong et al. All rights reserved. Effectiveness of the First Dose of BCG against Tuberculosis among HIV-Infected, Predominantly Immunodeficient Children Mon, 29 Jun 2015 09:25:03 +0000 The objective of this study was to estimate the protective effect of Bacille Calmette-Guérin (BCG) vaccine against tuberculosis among (predominantly immunodeficient) HIV-infected children in Angola. A hospital-based case-control study was conducted with 230 cases, children coinfected with tuberculosis, and 672 controls, HIV-infected children from the same hospital, aged 18 months to 13 years. The presence of a vaccination scar was taken as a proxy marker for BCG vaccination. The crude effectiveness was 8% (95% CI: −26 to 32) and the adjusted effectiveness was 30% (95% CI: −75 to 72). The present study suggests that BCG does not have a protective effect against tuberculosis among immunodeficient HIV-infected children. Since BCG is no longer given to HIV-infected children, the study may not be replicated. Accepting that these findings should be considered with caution, they are nonetheless likely to be the last estimate of BCG efficacy in a sufficiently powered study. Joaquim C. V. D. Van-Dunem, Laura C. Rodrigues, Luiz Claudio Arraes Alencar, Maria de Fátima Pessoa Militão-Albuquerque, and Ricardo Arraes de Alencar Ximenes Copyright © 2015 Joaquim C. V. D. Van-Dunem et al. All rights reserved. Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis Mon, 29 Jun 2015 08:47:56 +0000 This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway. Tsen-Ni Tsai, Jia-Jing Ho, Maw-Shung Liu, Tzu-Ying Lee, Mei-Chin Lu, Chia-Jen Liu, Li-Ju Huang, Sheng-I Lue, and Rei-Chen Yang Copyright © 2015 Tsen-Ni Tsai et al. All rights reserved. Advances in Diagnostic Imaging Technologies to Evaluate the Retina and the Optic Disc Mon, 29 Jun 2015 08:47:31 +0000 Antonio Ferreras, Michele Figus, Paolo Frezzotti, and Michele Iester Copyright © 2015 Antonio Ferreras et al. All rights reserved. A Novel Mutation of SMAD3 Identified in a Chinese Family with Aneurysms-Osteoarthritis Syndrome Mon, 29 Jun 2015 07:45:07 +0000 Aneurysms-osteoarthritis syndrome (AOS) is a recently delineated autosomal dominant disorder characterized by aneurysms, dissections, and tortuosity throughout the arterial tree in association with early onset osteoarthritis, mild craniofacial features, and skeletal and cutaneous anomalies. Previous studies have demonstrated that mutations in SMAD3, a key regulator of TGF-β signal transduction, contribute to AOS. Here, we investigated a family of three generations affected by AOS. A novel SMAD3 mutation, c.266G>A (p.C89Y), was identified and cosegregated with the affected individuals in this family. Our finding expands the mutation spectrum of SMAD3 gene and further strengthens the connection between the presence of aneurysms-osteoarthritis phenotype and SMAD3 mutations, which facilitates the understanding of the genotype-phenotype correlation of AOS. Wenwen Zhang, Min Zhou, Cheng Liu, Chen Liu, Tong Qiao, Dian Huang, Feng Ran, Wei Wang, Changjian Liu, and Zhao Liu Copyright © 2015 Wenwen Zhang et al. All rights reserved. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling Mon, 29 Jun 2015 07:31:44 +0000 A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles. Dmitry A. Chistiakov, Igor A. Sobenin, Alexander N. Orekhov, and Yuri V. Bobryshev Copyright © 2015 Dmitry A. Chistiakov et al. All rights reserved. The Role of Epigenetics in Arterial Calcification Mon, 29 Jun 2015 07:28:05 +0000 Arterial calcification is highly prevalent and correlated with cardiovascular mortality, especially in patients with ESRD or diabetes. The pathogenesis of arterial calcification is multifactorial, with both genetic and environmental factors being implicated. In recent years, several mechanisms contributing to arterial calcification have been proposed. However, these can only explain a small proportion of the variability in arterial calcification, which is a major obstacle for its prevention and management. Epigenetics has emerged as one of the most promising areas that may fill in some of the gaps in our current knowledge of the interaction between the environmental insults with gene regulation in the development of diseases. Epigenetics refers to heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Well-known components of epigenetic regulation include DNA methylation, histone modifications, and microRNAs. Epigenetics research in the regulation of arterial calcification has only recently been elucidated. In this review, we will summarise recent progress in epigenetic pathways involved in arterial calcification and discuss potential therapeutic interventions based on epigenetic mechanisms. Shan-Shan Wu, Xiao Lin, Ling-Qing Yuan, and Er-Yuan Liao Copyright © 2015 Shan-Shan Wu et al. All rights reserved. Alendronate-Eluting Biphasic Calcium Phosphate (BCP) Scaffolds Stimulate Osteogenic Differentiation Mon, 29 Jun 2015 07:18:39 +0000 Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN-) eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation. Sung Eun Kim, Young-Pil Yun, Deok-Won Lee, Eun Young Kang, Won Jae Jeong, Boram Lee, Myeong Seon Jeong, Hak Jun Kim, Kyeongsoon Park, and Hae-Ryong Song Copyright © 2015 Sung Eun Kim et al. All rights reserved. Evaluation of Synergetic Anticancer Activity of Berberine and Curcumin on Different Models of A549, Hep-G2, MCF-7, Jurkat, and K562 Cell Lines Mon, 29 Jun 2015 06:56:57 +0000 Ayurvedic system of medicine is using Berberis aristata and Curcuma longa herbs to treat different diseases including cancer. The study was performed to evaluate the synergetic anticancer activity of Berberine and Curcumin by estimating the inhibition of the cell proliferation by cytotoxicity assay using MTT method on specified human cell lines (A549, Hep-G2, MCF-7, Jurkat, and K562). All the cells were harvested from the culture and seeded in the 96-well assay plates at seeding density of 2.0 × 104 cells/well and were incubated for 24 hours. Test items Berberine with Curcumin (1 : 1), Curcumin 95% pure, and Berberine 95% pure were exposed at the concentrations of 1.25, 0.001, and 0.5 mg/mL, respectively, and incubated for a period of 48 hours followed by dispensing MTT solution (5 mg/mL). The cells were incubated at 37 ± 1°C for 4 hours followed by addition of DMSO for dissolving the formazan crystals and absorbance was read at 570 nm. Separate wells were prepared for positive control, controls (only medium with cells), and blank (only medium). The results had proven the synergetic anticancer activity of Berberine with Curcumin inducing cell death greater percentage of >77% when compared to pure curcumin with <54% and pure Berberine with <45% on average on all cell line models. Acharya Balakrishna and M. Hemanth Kumar Copyright © 2015 Acharya Balakrishna and M. Hemanth Kumar. All rights reserved. Semiautomatic, Quantitative Measurement of Aortic Valve Area Using CTA: Validation and Comparison with Transthoracic Echocardiography Mon, 29 Jun 2015 06:38:04 +0000 Objective. The aim of this work was to develop a fast and robust (semi)automatic segmentation technique of the aortic valve area (AVA) MDCT datasets. Methods. The algorithm starts with detection and cropping of Sinus of Valsalva on MPR image. The cropped image is then binarized and seed points are manually selected to create an initial contour. The contour moves automatically towards the edge of aortic AVA to obtain a segmentation of the AVA. AVA was segmented semiautomatically and manually by two observers in multiphase cardiac CT scans of 25 patients. Validation of the algorithm was obtained by comparing to Transthoracic Echocardiography (TTE). Intra- and interobserver variability were calculated by relative differences. Differences between TTE and MDCT manual and semiautomatic measurements were assessed by Bland-Altman analysis. Time required for manual and semiautomatic segmentations was recorded. Results. Mean differences from TTE were −0.19 (95% CI: −0.74 to 0.34) cm2 for manual and −0.10 (95% CI: −0.45 to 0.25) cm2 for semiautomatic measurements. Intra- and interobserver variability were 8.4 ± 7.1% and 27.6 ± 16.0% for manual, and 5.8 ± 4.5% and 16.8 ± 12.7% for semiautomatic measurements, respectively. Conclusion. Newly developed semiautomatic segmentation provides an accurate, more reproducible, and faster AVA segmentation result. V. Tuncay, N. Prakken, P. M. A. van Ooijen, R. P. J. Budde, T. Leiner, and M. Oudkerk Copyright © 2015 V. Tuncay et al. All rights reserved. MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes Sun, 28 Jun 2015 12:36:44 +0000 The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process. Xiaomin Zhang, Gohar Azhar, Emmanuel D. Williams, Steven C. Rogers, and Jeanne Y. Wei Copyright © 2015 Xiaomin Zhang et al. All rights reserved. miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress Sun, 28 Jun 2015 12:15:09 +0000 Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression. Ana Mondadori dos Santos, Laurent Metzinger, Oualid Haddad, Eléonore M’baya-Moutoula, Fatiha Taïbi, Nathalie Charnaux, Ziad A. Massy, Hanna Hlawaty, and Valérie Metzinger-Le Meuth Copyright © 2015 Ana Mondadori dos Santos et al. All rights reserved.