BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Bearing-Foreign Material Deposition on Retrieved Co-Cr Femoral Heads: Composition and Morphology Sun, 05 Jul 2015 10:33:09 +0000 Bearing-foreign material deposition onto a femoral head can occur from contact with an acetabular shell due to dislocation, reduction, or subluxation. The purpose of this study was to comprehensively characterize deposit regions on retrieved cobalt-chrome femoral heads from metal-on-polyethylene total hip arthroplasties that had experienced such adverse events. The morphology, topography, and composition of deposition regions were characterized using macrophotography, optical profilometry, scanning electron microscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy. The deposit areas were relatively large, they were much rougher than the surrounding undamaged clean areas, and they displayed several distinct morphologies. Titanium alloy elements were the predominant constituents. Calcium and phosphorous were also detected within the deposit areas, in a composition that could nucleate abrasive hydroxyapatite. In addition, tungsten-rich particles, likely present as tungsten carbide, were observed on top of the titanium deposits. The increased roughness associated with these deposition features would be expected to accelerate damage and wear of the opposing liner and hence accelerate the development of osteolysis. Nishant M. Tikekar, Anneliese D. Heiner, Thomas E. Baer, Karen M. Kruger, John J. Callaghan, Thomas D. Brown, and John J. Lannutti Copyright © 2015 Nishant M. Tikekar et al. All rights reserved. Sequence and Structure Analysis of Biological Molecules Based on Computational Methods Sun, 05 Jul 2015 09:51:33 +0000 Jia-Feng Yu, Yue-Dong Yang, Xiao Sun, and Ji-Hua Wang Copyright © 2015 Jia-Feng Yu et al. All rights reserved. An Improved Opposition-Based Learning Particle Swarm Optimization for the Detection of SNP-SNP Interactions Sun, 05 Jul 2015 09:49:43 +0000 SNP-SNP interactions have been receiving increasing attention in understanding the mechanism underlying susceptibility to complex diseases. Though many works have been done for the detection of SNP-SNP interactions, the algorithmic development is still ongoing. In this study, an improved opposition-based learning particle swarm optimization (IOBLPSO) is proposed for the detection of SNP-SNP interactions. Highlights of IOBLPSO are the introduction of three strategies, namely, opposition-based learning, dynamic inertia weight, and a postprocedure. Opposition-based learning not only enhances the global explorative ability, but also avoids premature convergence. Dynamic inertia weight allows particles to cover a wider search space when the considered SNP is likely to be a random one and converges on promising regions of the search space while capturing a highly suspected SNP. The postprocedure is used to carry out a deep search in highly suspected SNP sets. Experiments of IOBLPSO are performed on both simulation data sets and a real data set of age-related macular degeneration, results of which demonstrate that IOBLPSO is promising in detecting SNP-SNP interactions. IOBLPSO might be an alternative to existing methods for detecting SNP-SNP interactions. Junliang Shang, Yan Sun, Shengjun Li, Jin-Xing Liu, Chun-Hou Zheng, and Junying Zhang Copyright © 2015 Junliang Shang et al. All rights reserved. Regadenoson-Stress Dynamic Myocardial Perfusion Improves Diagnostic Performance of CT Angiography in Assessment of Intermediate Coronary Artery Stenosis in Asymptomatic Patients Sun, 05 Jul 2015 08:52:41 +0000 The prospective study included 54 asymptomatic high-risk patients who underwent coronary CT angiography (CTA) and regadenoson-induced stress CT perfusion (rsCTP). Diagnostic accuracy of significant stenosis (≥50%) determination was evaluated for CTA alone and CTA + rsCTP in 27 patients referred to ICA due to the positive rsCTP findings. Combined evaluation of CTA + rsCTP had higher diagnostic accuracy over CTA alone (per-segment: specificity 96 versus 68%, ; per-vessel: specificity 95 versus 75%, ) and high overruling rate of rsCTP was proved in intermediate stenosis (40–70%). Results demonstrate a significant additional value of rsCTP in the assessment of intermediate coronary artery stenosis found with CTA. Jan Baxa, Milan Hromádka, Jakub Šedivý, Lucie Štěpánková, Jiří Moláček, Bernhard Schmidt, Thomas Flohr, and Jiří Ferda Copyright © 2015 Jan Baxa et al. All rights reserved. The Relation between Nonverbal IQ and Postoperative CI Outcomes in Cochlear Implant Users: Preliminary Result Sun, 05 Jul 2015 08:28:19 +0000 Objectives. This study assessed the correlation between performance intelligence and the postoperative cochlear implant (CI) outcome in Korean-speaking children. In addition, the relationship between the performance intelligence subscales and the post-CI speech outcome was evaluated. Materials and Methods. Thirteen pediatric CI users (five males, eight females; median age at implantation 6.2 (range 1.3–14.2) years; median age at intelligence test 9.3 (range 5–16) years) who were tested using the Korean Educational Development Institute-Wechsler Intelligence Scale for children were studied. The correlations between the intelligence scores and 1-2 years postoperative Categories of Auditory Performance (CAP) scores and between subscales of performance and 1-2 years postoperative CAP scores were analyzed. Results. There was no correlation between the categories of verbal intelligence quotient (IQ) and performance IQ for “mentally retarded” and “average,” respectively (Spearman’s rho = 0.42, . There was a strong correlation between performance IQ and the postoperative CAP scale (Spearman’s rho = 0.8977, . “Picture arrangement” and “picture completion,” reflecting social cognition, were strongly correlated with the postoperative CAP scales. Conclusion. Performance intelligence, especially social cognition, was strongly related to the postoperative CI outcome of cochlear implant users. Therefore, auditory rehabilitation, including social rehabilitation, should maximize the postoperative CI outcomes. Mina Park, Jae-Jin Song, Seo Jin Oh, Min-Sup Shin, Jun Ho Lee, and Seung Ha Oh Copyright © 2015 Mina Park et al. All rights reserved. Written Language Ability in Mandarin-Speaking Children with Cochlear Implants Sun, 05 Jul 2015 08:05:46 +0000 Objectives. To examine narrative writing in cochlear implant (CI) children and understand the factors associated with unfavorable outcomes. Materials and Methods. Forty-five CI children in grades 2–6 participated in this study. They received CIs at 4.1 ± 2.1 years of age and had used them for 6.5 ± 2.7 years. A story-writing test was conducted and scored on 4 subscales: Total Number of Words, Words per Sentence, Morphosyntax, and Semantics. Scores more than 1.5 SD lower than the mean of the normal-hearing normative sample were considered problematic. Language and speech skills were examined. Results. Significantly more implanted students were problematic on “Total Number of Words” (), “Words per Sentence” (), and “Semantics” (). Poorer receptive language and auditory performance were independently associated with problematic “Total Number of Words” () and “Semantics” (), respectively. “Semantics” problem was more common in lower graders (grades 2–4) than in higher graders (grades 5-6; ). Conclusion. Implanted children tend to write stories that are shorter, worse-organized, and without a plot, while formulating morphosyntactically correct sentences. Special attention is required on their auditory and language performances, which could lead to written language problems. Che-Ming Wu, Hui-Chen Ko, Yen-An Chen, Yung-Ting Tsou, and Wei-Chieh Chao Copyright © 2015 Che-Ming Wu et al. All rights reserved. Modeling of Auditory Neuron Response Thresholds with Cochlear Implants Sun, 05 Jul 2015 08:04:26 +0000 The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement), electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device). The electrical response, measured using auto-NRT (neural responses telemetry) algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = −0.11 ± 0.02, ), the scalar placement of the electrodes (β = −8.50 ± 1.97, ), and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF). Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas. Frederic Venail, Thibault Mura, Mohamed Akkari, Caroline Mathiolon, Sophie Menjot de Champfleur, Jean Pierre Piron, Marielle Sicard, Françoise Sterkers-Artieres, Michel Mondain, and Alain Uziel Copyright © 2015 Frederic Venail et al. All rights reserved. Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies Sun, 05 Jul 2015 07:58:49 +0000 Background. Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. Methods. The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. Results. Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). Conclusions. Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if central nervous system anomalies represent a negative prognostic factor that is made worse by the concomitant presence of cochlear malformations. Common cavity and stenosis of the internal auditory canal (less than 2 mm) are negative prognostic factors even if brain lesions are absent. Micol Busi, Monica Rosignoli, Alessandro Castiglione, Federica Minazzi, Patrizia Trevisi, Claudia Aimoni, Ferdinando Calzolari, Enrico Granieri, and Alessandro Martini Copyright © 2015 Micol Busi et al. All rights reserved. Hypoxia Induces a Metabolic Shift and Enhances the Stemness and Expansion of Cochlear Spiral Ganglion Stem/Progenitor Cells Sun, 05 Jul 2015 07:45:48 +0000 Previously, we demonstrated that hypoxia (1% O2) enhances stemness markers and expands the cell numbers of cochlear stem/progenitor cells (SPCs). In this study, we further investigated the long-term effect of hypoxia on stemness and the bioenergetic status of cochlear spiral ganglion SPCs cultured at low oxygen tensions. Spiral ganglion SPCs were obtained from postnatal day 1 CBA/CaJ mouse pups. The measurement of oxygen consumption rate, extracellular acidification rate (ECAR), and intracellular adenosine triphosphate levels corresponding to 20% and 5% oxygen concentrations was determined using a Seahorse XF extracellular flux analyzer. After low oxygen tension cultivation for 21 days, the mean size of the hypoxia-expanded neurospheres was significantly increased at 5% O2; this correlated with high-level expression of hypoxia-inducible factor-1 alpha (Hif-1α), proliferating cell nuclear antigen (PCNA), cyclin D1, Abcg2, nestin, and Nanog proteins but downregulated expression of p27 compared to that in a normoxic condition. Low oxygen tension cultivation tended to increase the side population fraction, with a significant difference found at 5% O2 compared to that at 20% O2. In addition, hypoxia induced a metabolic energy shift of SPCs toward higher basal ECARs and higher maximum mitochondrial respiratory capacity but lower proton leak than under normoxia, where the SPC metabolism was switched toward glycolysis in long-term hypoxic cultivation. Hsin-Chien Chen, Jen-Tin Lee, Cheng-Ping Shih, Ting-Ting Chao, Huey-Kang Sytwu, Shiue-Li Li, Mei-Cho Fang, Hang-Kang Chen, Yi-Chun Lin, Chao-Yin Kuo, and Chih-Hung Wang Copyright © 2015 Hsin-Chien Chen et al. All rights reserved. A Fast Cluster Motif Finding Algorithm for ChIP-Seq Data Sets Sun, 05 Jul 2015 07:40:37 +0000 New high-throughput technique ChIP-seq, coupling chromatin immunoprecipitation experiment with high-throughput sequencing technologies, has extended the identification of binding locations of a transcription factor to the genome-wide regions. However, the most existing motif discovery algorithms are time-consuming and limited to identify binding motifs in ChIP-seq data which normally has the significant characteristics of large scale data. In order to improve the efficiency, we propose a fast cluster motif finding algorithm, named as FCmotif, to identify the motifs in large scale ChIP-seq data set. It is inspired by the emerging substrings mining strategy to find the enriched substrings and then searching the neighborhood instances to construct PWM and cluster motifs in different length. FCmotif is not following the OOPS model constraint and can find long motifs. The effectiveness of proposed algorithm has been proved by experiments on the ChIP-seq data sets from mouse ES cells. The whole detection of the real binding motifs and processing of the full size data of several megabytes finished in a few minutes. The experimental results show that FCmotif has advantageous to deal with the motif finding in the ChIP-seq data; meanwhile it also demonstrates better performance than other current widely-used algorithms such as MEME, Weeder, ChIPMunk, and DREME. Yipu Zhang and Ping Wang Copyright © 2015 Yipu Zhang and Ping Wang. All rights reserved. Highly Flexible Silicone Coated Neural Array for Intracochlear Electrical Stimulation Sun, 05 Jul 2015 06:58:52 +0000 We present an effective method for tailoring the flexibility of a commercial thin-film polymer electrode array for intracochlear electrical stimulation. Using a pneumatically driven dispensing system, an average  μm (mean ± SD) thickness layer of silicone adhesive coating was applied to stiffen the underside of polyimide multisite arrays. Additional silicone was applied to the tip to protect neural tissue during insertion and along the array to improve surgical handling. Each array supported 20 platinum sites (180 μm dia., 250 μm pitch), spanning nearly 28 mm in length and 400 μm in width. We report an average intracochlear stimulating current threshold of  μA to evoke an auditory brainstem response in 7 acutely deafened felines. A total of 10 arrays were each inserted through a round window approach into the cochlea’s basal turn of eight felines with one delamination occurring upon insertion (preliminary results of the in vivo data presented at the 48th Annual Meeting American Neurotology Society, Orlando, FL, April 2013, and reported in Van Beek-King 2014). Using microcomputed tomography imaging (50 μm resolution), distances ranging from 100 to 565 μm from the cochlea’s central modiolus were measured. Our method combines the utility of readily available commercial devices with a straightforward postprocessing step on the order of 24 hours. P. Bhatti, J. Van Beek-King, A. Sharpe, J. Crawford, S. Tridandapani, B. McKinnon, and D. Blake Copyright © 2015 P. Bhatti et al. All rights reserved. Evaluation of Intracochlear Trauma Caused by Insertion of Cochlear Implant Electrode Arrays through Different Quadrants of the Round Window Sun, 05 Jul 2015 06:36:19 +0000 Hypothesis. This study aimed to evaluate whether there is a difference in the degree of intracochlear trauma when the cochlear implant electrode arrays is inserted through different quadrants of the round window membrane. Background. The benefits of residual hearing preservation in cochlear implant recipients have promoted the development of atraumatic surgeries. Minimal trauma during electrode insertion is crucial for residual hearing preservation. Methods. In total, 25 fresh human temporal bones were subjected to mastoidectomy and posterior tympanotomy. The cochlear implant electrode array was inserted through the anterosuperior quadrant of the round window membrane in 50% of the bones and through the anteroinferior quadrant in the remaining 50%. The temporal bones were dehydrated, embedded in epoxy, serially polished, stained, viewed through a stereomicroscope, and photographed with the electrode arrays in situ. The resulting images were analyzed for signs of intracochlear trauma. Results. Histological examinations revealed varying degrees of damage to the intracochlear structures, although the incidence and severity of intracochlear trauma were not influenced by the quadrant of insertion. Conclusions. The incidence and severity of intracochlear trauma were similar in all samples, irrespective of electrode array insertion through the anterosuperior or anteroinferior quadrant of the round window membrane. Graziela de Souza Queiroz Martins, Rubens Vuono Brito Neto, Robinson Koji Tsuji, Eloisa Maria Mello Santiago Gebrim, and Ricardo Ferreira Bento Copyright © 2015 Graziela de Souza Queiroz Martins et al. All rights reserved. Stability Testing of a Wide Bone-Anchored Device after Surgery without Skin Thinning Sun, 05 Jul 2015 06:29:27 +0000 Objective. To longitudinally follow the osseointegration using Resonance Frequency Analysis (RFA) for different lengths of abutment on a new wide bone-anchored implant, introduced with the non-skin thinning surgical technique. Study Design. A single-center, prospective 1 year study following adults with bone-anchored hearing implants. Materials and Methods. Implantation was performed and followed for a minimum of 1 year. All patients were operated on according to the tissue preserving technique. A 4.5 mm wide fixture (Oticon Medical) with varying abutments (9 to 12 mm) was used and RFA was tested 1 week, 7 weeks, 6 months, and 12 months later. Implant Stability Quotient (ISQ), was measured from 1 to 100. Stability was compared to a group of patients implanted with another brand (Cochlear BI400) of 4.5 mm fixtures. Results. All 10 adults concluded the study. None of the participants lost their implant during the test period indicating a good anchoring of abutments to the wide fixture tested. Stability testing was shown to vary depending on abutment length and time after surgery and with higher values for shorter abutments and increasing values over the first period of time. One patient changed the abutment from 12 to 9 mm and another from a 9 to a 12 during the year. No severe skin problems, numbness around the implant, or cosmetic problems arose. Conclusion. After 1 year of follow-up, combination of a wide fixture implant and the non-skin thinning surgical technique indicates a safe procedure with good stability and no abutment losses. Malou Hultcrantz Copyright © 2015 Malou Hultcrantz. All rights reserved. Cochlear Dummy Electrodes for Insertion Training and Research Purposes: Fabrication, Mechanical Characterization, and Experimental Validation Sun, 05 Jul 2015 06:27:57 +0000 To develop skills sufficient for hearing preservation cochlear implant surgery, surgeons need to perform several electrode insertion trials in ex vivo temporal bones, thereby consuming relatively expensive electrode carriers. The objectives of this study were to evaluate the insertion characteristics of cochlear electrodes in a plastic scala tympani model and to fabricate radio opaque polymer filament dummy electrodes of equivalent mechanical properties. In addition, this study should aid the design and development of new cochlear electrodes. Automated insertion force measurement is a new technique to reproducibly analyze and evaluate the insertion dynamics and mechanical characteristics of an electrode. Mechanical properties of MED-EL’s FLEX28, FLEX24, and FLEX20 electrodes were assessed with the help of an automated insertion tool. Statistical analysis of the overall mechanical behavior of the electrodes and factors influencing the insertion force are discussed. Radio opaque dummy electrodes of comparable characteristics were fabricated based on insertion force measurements. The platinum-iridium wires were replaced by polymer filament to provide sufficient stiffness to the electrodes and to eradicate the metallic artifacts in X-ray and computed tomography (CT) images. These low-cost dummy electrodes are cheap alternatives for surgical training and for in vitro, ex vivo, and in vivo research purposes. Jan-Philipp Kobler, Anandhan Dhanasingh, Raphael Kiran, Claude Jolly, and Tobias Ortmaier Copyright © 2015 Jan-Philipp Kobler et al. All rights reserved. Big Data Analytics in Healthcare Thu, 02 Jul 2015 12:06:04 +0000 The rapidly expanding field of big data analytics has started to play a pivotal role in the evolution of healthcare practices and research. It has provided tools to accumulate, manage, analyze, and assimilate large volumes of disparate, structured, and unstructured data produced by current healthcare systems. Big data analytics has been recently applied towards aiding the process of care delivery and disease exploration. However, the adoption rate and research development in this space is still hindered by some fundamental problems inherent within the big data paradigm. In this paper, we discuss some of these major challenges with a focus on three upcoming and promising areas of medical research: image, signal, and genomics based analytics. Recent research which targets utilization of large volumes of medical data while combining multimodal data from disparate sources is discussed. Potential areas of research within this field which have the ability to provide meaningful impact on healthcare delivery are also examined. Ashwin Belle, Raghuram Thiagarajan, S. M. Reza Soroushmehr, Fatemeh Navidi, Daniel A. Beard, and Kayvan Najarian Copyright © 2015 Ashwin Belle et al. All rights reserved. Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and Perioperative Management Thu, 02 Jul 2015 09:09:22 +0000 Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring. Both United States and European Guidelines recommend NOACs for stroke prevention in patients with atrial fibrillation. This review discusses each of the NOACs, along with their efficacy and safety data. It explores the most recent guidelines regarding their perioperative use in atrial fibrillation patients. It also discusses bleeding complications, perioperative management, and reversal agents. Fadi Shamoun, Hiba Obeid, and Harish Ramakrishna Copyright © 2015 Fadi Shamoun et al. 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.