BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Retrograde Intrarenal Surgery versus Percutaneous Lithotripsy to Treat Renal Stones 2-3 cm in Diameter Tue, 03 Mar 2015 12:21:43 +0000 Objective. Retrograde intrarenal surgery (RIRS) performed using a flexible ureterorenoscope marked the beginning of a new era in urology. Today, even staghorn stones are successfully treated via RIRS. The recommended treatment for larger stones is percutaneous nephrolithotomy (PNL). However, the question of whether PNL or RIRS should be the first-line treatment option for larger stones remains controversial. In this study, we contribute to the debate by comparing the success and complication rates of PNL and RIRS that were used to treat renal pelvis stones 2-3 cm in diameter. Materials and Methods. The medical records of 154 patients (74 PNL, 80 RIRS) were retrospectively evaluated. PNL patients were placed in Group 1 and RIRS patients in Group 2. Results. The complete stone-free rates were 95.5% in the PNL group and 80.6% in the RIRS group 1 month postoperatively (). The respective complication rates (evaluated using the Clavien system) were 13.5% and 8.8% (). Conclusions. RIRS affords a comparable success rate, causes fewer complications than PNL, and seems to be a promising alternative to PNL when larger stones are to be treated. Prospective randomized controlled trials are needed to confirm these findings. Kursad Zengin, Serhat Tanik, Nihat Karakoyunlu, Nevzat Can Sener, Sebahattin Albayrak, Can Tuygun, Hasan Bakirtas, M. Abdurrahim Imamoglu, and Mesut Gurdal Copyright © 2015 Kursad Zengin et al. All rights reserved. Calcium Homeostasis and ER Stress in Control of Autophagy in Cancer Cells Tue, 03 Mar 2015 12:01:06 +0000 Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca2+ homeostasis perturbation and starvation. Several Ca2+ channels like voltage-gated T- and L-type channels, IP3 receptors, or CRAC are involved in autophagy regulation. Glucose transporters, mainly from GLUT family, which are often upregulated in cancer, are also prominent targets for autophagy induction. Signals from both Ca2+ perturbations and glucose transport blockage might be integrated at UPR and ER stress activation. Molecular pathways such as IRE 1-JNK-Bcl-2, PERK-eIF2α-ATF4, or ATF6-XBP 1-ATG are related to autophagy induced through ER stress. Moreover ER molecular chaperones such as GRP78/BiP and transcription factors like CHOP participate in regulation of ER stress-mediated autophagy. Autophagy modulation might be promising in anticancer therapies; however, it is a context-dependent matter whether inhibition or activation of autophagy leads to tumor cell death. Elżbieta Kania, Beata Pająk, and Arkadiusz Orzechowski Copyright © 2015 Elżbieta Kania et al. All rights reserved. Thermal Tomography Imaging in Photonic Traditional Chinese Medicine Information Therapy with Holistic Effect for Health Whole Nursing Tue, 03 Mar 2015 11:49:32 +0000 A photonic traditional Chinese medicine (TCM) information therapy was developed that has applications in whole health nursing including the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases as well as the conditioning of the subhealth state. This therapy utilizes the beam of a 630 nm LED light to irradiate the oropharynx, while simultaneously employing two beams of 650 nm LED light to irradiate corresponding acupuncture points resulting in a synergistic outcome. This method was named “1 + 2 phototherapy.” The principle mechanism of the therapy is a series of photon induced biological effects that are triggered by stimulating the photosensitive tissues of the oropharynx. This tissue includes the oral mucosa, capillaries, lymph nodes, saliva glands, nerves, and Jingluo and is stimulated by light beams of certain photon energy and imitative acupuncture information. Thermal tomography imaging shows that the average temperature of the upper-body was improved significantly after oropharyngeal irradiation under irradiation of “Futu point”: the heat radiation of the spine, as well as chest, shoulders, arms, and clavicle, increased under irradiation of “Hoku,” whereas the overall average temperature was below the temperature before irradiation. The experiment indicates that this therapy can promote blood circulation, regulate varied physiological parameters, and have holistic effects in whole health nursing. Binggang Ye, Zhouyi Guo, Hanchuan Huang, and Xicheng Yang Copyright © 2015 Binggang Ye et al. All rights reserved. Nucleofection of Rat Pheochromocytoma PC-12 Cells with Human Mutated Beta-Amyloid Precursor Protein Gene (APP-sw) Leads to Reduced Viability, Autophagy-Like Process, and Increased Expression and Secretion of Beta Amyloid Tue, 03 Mar 2015 11:35:53 +0000 Pheochromocytoma PC-12 cells are immune to physiological stimuli directed to evoke programmed cell death. Besides, metabolic inhibitors are incapable of sensitizing PC-12 cells to extrinsic or intrinsic apoptosis unless they are used in toxic concentrations. Surprisingly, these cells become receptive to cell deletion after human APP-sw gene expression. We observed reduced cell viability in GFP vector + APP-sw-nucleofected cells (drop by 36%) but not in GFP vector − or GFP vector + APP-wt-nucleofected cells. Lower viability was accompanied by higher expression of A 1-16 and elevated secretion of A 1-40 (in average 53.58 pg/mL). At the ultrastructural level autophagy-like process was demonstrated to occur in APP-sw-nucleofected cells with numerous autophagosomes and multivesicular bodies but without autolysosomes. Human APP-sw gene is harmful to PC-12 cells and cells are additionally driven to incomplete autophagy-like process. When stimulated by TRAIL or nystatin, CLU protein expression accompanies early phase of autophagy. Beata Pająk, Elżbieta Kania, and Arkadiusz Orzechowski Copyright © 2015 Beata Pająk et al. All rights reserved. Combined Epidermal Growth Factor Receptor and Beclin1 Autophagic Protein Expression Analysis Identifies Different Clinical Presentations, Responses to Chemo- and Radiotherapy, and Prognosis in Glioblastoma Tue, 03 Mar 2015 09:54:03 +0000 Dysregulated EGFR in glioblastoma may inactivate the key autophagy protein Beclin1. Each of high EGFR and low Beclin1 protein expression, independently, has been associated with tumor progression and poor prognosis. High (H) compared to low (L) expression of EGFR and Beclin1 is here correlated with main clinical data in 117 patients after chemo- and radiotherapy. H-EGFR correlated with low Karnofsky performance and worse neurological performance status, higher incidence of synchronous multifocality, poor radiological evidence of response, shorter progression disease-free (PDFS), and overall survival (OS). H-Beclin1 cases showed better Karnofsky performance status, higher incidence of objective response, longer PDFS, and OS. A mutual strengthening effect emerges in correlative power of stratified L-EGFR and H-Beclin1 expression with incidence of radiological response after treatment, unifocal disease, and better prognosis, thus identifying an even longer OS group (30 months median OS compared to 18 months in L-EGFR, 15 months in H-Beclin1, and 11 months in all GBs) (). Combined L-EGFR + H-Beclin1 expression may represent a biomarker in identifying relatively favorable clinical presentations and prognosis, thus envisaging possible EGFR/Beclin1-targeted therapies. Paolo Tini, Giuseppe Belmonte, Marzia Toscano, Clelia Miracco, Silvia Palumbo, Pierpaolo Pastina, Giuseppe Battaglia, Valerio Nardone, Marie Aimée Gloria Munezero Butorano, Armando Masucci, Alfonso Cerase, and Luigi Pirtoli Copyright © 2015 Paolo Tini et al. All rights reserved. Gene Network Exploration of Crosstalk between Apoptosis and Autophagy in Chronic Myelogenous Leukemia Tue, 03 Mar 2015 09:24:08 +0000 Background. Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear. Results. Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks. Conclusion. The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy. Fengfeng Wang, William C. S. Cho, Lawrence W. C. Chan, S. C. Cesar Wong, Nancy B. Y. Tsui, Parco M. Siu, S. P. Yip, and Benjamin Y. M. Yung Copyright © 2015 Fengfeng Wang et al. All rights reserved. The Relationship of CSF and Plasma Cytokine Levels in HIV Infected Patients with Neurocognitive Impairment Tue, 03 Mar 2015 09:19:15 +0000 Although HAD is now rare due to HAART, the milder forms of HAND persist in HIV-infected patients. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. The levels of cytokines in CSF were associated with neurocognitive impairment in HIV infection. However, the changes of cytokines involved in cognition impairment in plasma have not been shown, and their relationships between CSF and plasma require to be addressed. We compared cytokine levels in paired CSF and plasma samples from HIV-infected individuals with or without neurocognitive impairment. Cytokine concentrations were measured by Luminex xMAP. In comparing the expression levels of cytokines in plasma and CSF, IFN-α2, IL-8, IP-10, and MCP-1 were significantly higher in CSF. Eotaxin was significantly higher in plasma, whereas G-CSF showed no difference between plasma and CSF. G-CSF , IL-8 , IP-10 , and MCP-1 in CSF showed significant difference between HIV-CI and HIV-NC group, which may indicate their relationship to HIV associated neurocognitive impairment. In addition, G-CSF and IP-10 in plasma were significantly higher in HIV-CI than HIV-NC. The consistent changes of G-CSF and IP-10 in paired plasma and CSF samples might enhance their potential for predicting HAND. Lin Yuan, An Liu, Luxin Qiao, Bo Sheng, Meng Xu, Wei Li, and Dexi Chen Copyright © 2015 Lin Yuan et al. All rights reserved. An Open-Label Uncontrolled, Multicenter Study for the Evaluation of the Efficacy and Safety of the Dermal Filler Princess VOLUME in the Treatment of Nasolabial Folds Tue, 03 Mar 2015 09:19:14 +0000 The dermal filler Princess VOLUME is a highly cross-linked, viscoelastic hyaluronic acid injectable gel implant used for aesthetic treatment. To evaluate the efficacy and safety of Princess VOLUME in the treatment of nasolabial folds, an open-label uncontrolled, multicenter study was conducted. Forty-eight subjects were recruited who had moderate to deep wrinkles, according to the Modified Fitzpatrick Wrinkle Scale (MFWS). Subjects received Princess VOLUME in both nasolabial folds at Day 0. Nasolabial fold severity was evaluated at 30, 90, 180, and 270 days after treatment, using the MFWS and the Global Aesthetic Improvement Scale (GAIS). Adverse events and treatment site reactions were recorded. Among the 48 subjects, 93.8% were female with a median age of 52 years. There were significant improvements in the MFWS scores at 30, 180, and 270 days after treatment compared with those at baseline, with a mean decrease of 1.484 (±0.408), 1.309 (±0.373), and 1.223 (±0.401), respectively; hence the primary endpoint was achieved and clinical efficacy demonstrated. Princess VOLUME was well tolerated, and most adverse events were injection site reactions of mild to moderate severity. Subject satisfaction (97.9%), subject recommendation of the treatment (93.6%), and investigators GAIS scores (97.9% improvement) were high. Daisy Kopera, Michael Palatin, Rolf Bartsch, Katrin Bartsch, Maria O’Rourke, Sonja Höller, Renate R. Baumgartner, and Martin Prinz Copyright © 2015 Daisy Kopera et al. All rights reserved. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury Tue, 03 Mar 2015 09:16:11 +0000 Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. Wei Zhang, Yuan Gao, Yan Zhou, Jianheng Liu, Licheng Zhang, Anhua Long, Lihai Zhang, and Peifu Tang Copyright © 2015 Wei Zhang et al. All rights reserved. Controversial Indications for Sentinel Lymph Node Biopsy in Breast Cancer Patients Tue, 03 Mar 2015 07:48:13 +0000 Sentinel lymph node biopsy (SLNB) emerged in the 1990s as a new technique in the surgical management of the axilla for patients with early breast cancer, resulting in lower complication rates and better quality of life than axillary lymph node dissection (ALND). Today SLNB is firmly established in the armamentarium of clinicians treating breast cancer, but several questions remain. The goal of this paper is to review recent work addressing 4 questions that have been the subject of debate in the use of SLNB in the past few years: (a) What is the implication of finding micrometastases in the sentinel nodes? (b) Is ALND necessary in all patients who have a positive SLNB? (c) How accurate is SLNB after neoadjuvant therapy? (d) Can SLNB be used to stage the axilla in locally recurrent breast cancer following breast surgery with or without prior axillary surgery? Hazem Assi, Eman Sbaity, Mahmoud Abdelsalam, and Ali Shamseddine Copyright © 2015 Hazem Assi et al. All rights reserved. Expression of MMP-9 and VEGF in Meningiomas and Their Correlation with Peritumoral Brain Edema Tue, 03 Mar 2015 07:47:40 +0000 Meningiomas constitute up to 13% of all intracranial tumors. The predictive factors for meningioma have not been unambiguously defined; however some limited data suggest that the expression of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be associated with the presence of peritumoral brain edema (PTBE) and worse clinical outcome. The aim of this study was to analyze the expressions of MMP-9 and VEGF in a group of meningiomas of various grades and to study associations between these two markers and PTBE. The study included patients with supratentorial meningiomas. The patients were divided into low- (G1) and high-grade meningiomas (G2 and G3). PTBE was assessed on MRI. The expressions of VEGF and MMP-9 were determined immunohistochemically. The expression of MMP-9 was observed significantly more often in G3 meningiomas than in lower grade tumors. The presence of stage II or III PTBE was associated with a significant increase in MMP-9 expression. The expression of VEGF did not differ across the PTBE stages. Our findings point to a significant role of MMP-9 and VEGF in the pathogenesis of peritumoral brain edema in low- and high-grade meningiomas. Joanna Reszec, Adam Hermanowicz, Robert Rutkowski, Grzegorz Turek, Zenon Mariak, and Lech Chyczewski Copyright © 2015 Joanna Reszec et al. All rights reserved. Ankylosing Spondylitis and Posture Control: The Role of Visual Input Tue, 03 Mar 2015 06:24:22 +0000 Objectives. To assess the motor control during quiet stance in patients with established ankylosing spondylitis (AS) and to evaluate the effect of visual input on the maintenance of a quiet posture. Methods. 12 male AS patients (mean age 50.1 ± 13.2 years) and 12 matched healthy subjects performed 2 sessions of 3 trials in quiet stance, with eyes open (EO) and with eyes closed (EC) on a baropodometric platform. The oscillation of the centre of feet pressure (CoP) was acquired. Indices of stability and balance control were assessed by the sway path (SP) of the CoP, the frequency bandwidth (FB1) that includes the 80% of the area under the amplitude spectrum, the mean amplitude of the peaks (MP) of the sway density curve (SDC), and the mean distance (MD) between 2 peaks of the SDC. Results. In severe AS patients, the MD between two peaks of the SDC and the SP of the center of feet pressure were significantly higher than controls during both EO and EC conditions. The MP was significantly reduced just on EC. Conclusions. Ankylosing spondylitis exerts negative effect on postural stability, not compensable by visual inputs. Our findings may be useful in the rehabilitative management of the increased risk of falling in AS. Alessandro Marco De Nunzio, Salvatore Iervolino, Carmela Zincarelli, Luisa Di Gioia, Giuseppe Rengo, Vincenzo Multari, Rosario Peluso, Matteo Nicola Dario Di Minno, and Nicola Pappone Copyright © 2015 Alessandro Marco De Nunzio et al. All rights reserved. cspA Influences Biofilm Formation and Drug Resistance in Pathogenic Fungus Aspergillus fumigatus Tue, 03 Mar 2015 06:09:26 +0000 The microbial cell wall plays a crucial role in biofilm formation and drug resistance. cspA encodes a repeat-rich glycophosphatidylinositol-anchored cell wall protein in the pathogenic fungus Aspergillus fumigatus. To determine whether cspA has a significant impact on biofilm development and sensitivity to antifungal drugs in A. fumigatus, a ΔcspA mutant was constructed by targeted gene disruption, and we then reconstituted the mutant to wild type by homologous recombination of a functional cspA gene. Deletion of cspA resulted in a rougher conidial surface, reduced biofilm formation, decreased resistance to antifungal agents, and increased internalization by A549 human lung epithelial cells, suggesting that cspA not only participates in maintaining the integrity of the cell wall, but also affects biofilm establishment, drug response, and invasiveness of A. fumigatus. Zhongqi Fan, Zhe Li, Zongge Xu, Hongyan Li, Lixiang Li, Cong Ning, Lin Ma, Xiangli Xie, Guangyi Wang, and Huimei Yu Copyright © 2015 Zhongqi Fan et al. All rights reserved. Antioxidant Strategies in the Management of Diabetic Neuropathy Mon, 02 Mar 2015 15:04:39 +0000 Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants. Ayodeji Babatunde Oyenihi, Ademola Olabode Ayeleso, Emmanuel Mukwevho, and Bubuya Masola Copyright © 2015 Ayodeji Babatunde Oyenihi et al. All rights reserved. Predictors of Mortality for Nursing Home-Acquired Pneumonia: A Systematic Review Mon, 02 Mar 2015 14:47:55 +0000 Background. Current risk stratification tools, primarily used for CAP, are suboptimal in predicting nursing home acquired pneumonia (NHAP) outcome and mortality. We conducted a systematic review to evaluate current evidence on the usefulness of proposed predictors of NHAP mortality. Methods. PubMed (MEDLINE), EMBASE, and CINAHL databases were searched for articles published in English between January 1978 and January 2014. The literature search elicited a total of 666 references; 580 were excluded and 20 articles met the inclusion criteria for the final analysis. Results. More studies supported the Pneumonia Severity Index (PSI) as a superior predictor of NHAP severity. Fewer studies suggested CURB-65 and SOAR (especially for the need of ICU care) as useful predictors for NHAP mortality. There is weak evidence for biomarkers like C-reactive protein and copeptin as prognostic tools. Conclusion. The evidence supports the use of PSI as the best available indicator while CURB-65 may be an alternative prognostic indicator for NHAP mortality. Overall, due to the paucity of information, biomarkers may not be as effective in this role. Larger prospective studies are needed to establish the most effective predictor(s) or combination scheme to help clinicians in decision-making related to NHAP mortality. Naveen Dhawan, Naushira Pandya, Michael Khalili, Manuel Bautista, Anurag Duggal, Jaya Bahl, and Vineet Gupta Copyright © 2015 Naveen Dhawan et al. All rights reserved. Proteomic Analysis of Human Brain Microvascular Endothelial Cells Reveals Differential Protein Expression in Response to Enterovirus 71 Infection Mon, 02 Mar 2015 12:49:57 +0000 2D DIGE technology was employed on proteins prepared from human brain microvascular endothelial cells (HBMEC), to study the differentially expressed proteins in cells at 0 h, 1 h, 16 h, and 24 h after infection. Proteins found to be differentially expressed were identified with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDITOF/TOF MS) analysis. We identified 43 spots showing changes of at least 2.5 fold up- or downregulated expressions in EV71-infected cells at different time when comparing to control, and 28 proteins could be successfully identified by MALDI TOF/TOF mass spectrometry analysis. 4 proteins were significantly upregulated, and 6 proteins were downregulated, another 18 proteins were different expression at different incubation time. We identified changes in the expression of 12 cellular metabolism-related proteins, 5 molecules involved in cytoskeleton, 3 molecules involved in energy metabolism, 2 molecules involved in signal transduction, 1 molecule involved in the ubiquitin-proteasome pathway, 1 molecule involved in cell cycle, 1 molecule involved in apoptosis-related protein, 1 molecular chaperone, and 2 unknown proteins. These findings build up a comprehensive profile of the HBMEC proteome and provide a useful basis for further analysis of the pathogenic mechanism that underlies EV71 infections to induce severe neural complications. Wenying Luo, Jiayu Zhong, Wei Zhao, Jianjun Liu, Renli Zhang, Liang Peng, Wenxu Hong, Sheng He Huang, and Hong Cao Copyright © 2015 Wenying Luo et al. All rights reserved. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis Mon, 02 Mar 2015 12:27:00 +0000 Viral-myocarditis is an important cause of heart failure for which no specific treatment is available. We previously showed the neuropeptide substance P (SP) is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (EMCV). The current studies determined if pharmacological inhibition of SP-signaling via its high affinity receptor, NK1R and downstream G-protein, Ras homolog gene family, member-A (RhoA), will be beneficial in viral-myocarditis. Aprepitant (1.2 mg/kg), a SP-receptor antagonist, or fasudil (10 mg/kg), a RhoA inhibitor, or saline control was administered daily to mice orally for 3 days, prior to, or 5 days following, intraperitoneal infection with and without 50 PFU of EMCV, following which disease assessment studies, including echocardiogram and cardiac Doppler were performed in day 14 after infection. Pretreatment and posttreatment with aprepitant significantly reduced mortality, heart and cardiomyocyte size, and cardiac viral RNA levels ( all, ANOVA). Only aprepitant pretreatment improved heart functions; it significantly decreased end systolic diameter, improved fractional shortening, and increased peak aortic flow velocity ( all, ANOVA). Pre- or posttreatment with fasudil did not significantly impact disease manifestations. These findings indicate that SP contributes to cardiac-remodeling and dysfunction following ECMV infection via its high affinity receptor, but not through the Rho-A pathway. These studies suggest that SP-receptor antagonism may be a novel therapeutic-option for patients with viral-myocarditis. Prema Robinson, George E. Taffet, Nikita Engineer, Mitra Khumbatta, Bahrom Firozgary, Corey Reynolds, Thuy Pham, Tushar Bulsara, and Gohar Firozgary Copyright © 2015 Prema Robinson et al. All rights reserved. Cytotoxicity of Cyclodipeptides from Pseudomonas aeruginosa PAO1 Leads to Apoptosis in Human Cancer Cell Lines Mon, 02 Mar 2015 12:26:15 +0000 Pseudomonas aeruginosa is an opportunistic pathogen of plants and animals, which produces virulence factors in order to infect or colonize its eukaryotic hosts. Cyclodipeptides (CDPs) produced by P. aeruginosa exhibit cytotoxic properties toward human tumor cells. In this study, we evaluated the effect of a CDP mix, comprised of cyclo(L-Pro-L-Tyr), cyclo(L-Pro-L-Val), and cyclo(L-Pro-L-Phe) that were isolated from P. aeruginosa, on two human cancer cell lines. Our results demonstrated that the CDP mix promoted cell death in cultures of the HeLa cervical adenocarcinoma and Caco-2 colorectal adenocarcinoma cell lines in a dose-dependent manner, with a 50% inhibitory concentration (IC50) of 0.53 and 0.66 mg/mL, for HeLa and Caco-2 cells, respectively. Flow cytometric analysis, using annexin V and propidium iodide as apoptosis and necrosis indicators, respectively, clearly showed that HeLa and Caco-2 cells exhibited apoptotic characteristics when treated with the CDP mix at a concentration <0.001 mg/mL. IC50 values for apoptotic cells in HeLa and Caco-2 cells were 6.5 × 10−5 and 1.8 × 10−4 mg/mL, respectively. Our results indicate that an apoptotic pathway is involved in the inhibition of cell proliferation caused by the P. aeruginosa CDP mix. Dolores Vázquez-Rivera, Omar González, Jaquelina Guzmán-Rodríguez, Alma L. Díaz-Pérez, Alejandra Ochoa-Zarzosa, José López-Bucio, Víctor Meza-Carmen, and Jesús Campos-García Copyright © 2015 Dolores Vázquez-Rivera et al. All rights reserved. Recent Developments of Carbonic Anhydrase Inhibitors as Potential Drugs Mon, 02 Mar 2015 12:21:01 +0000 Jamshed Iqbal, Mariya Al-Rashida, Serdar Durdagi, Vincenzo Alterio, and Anna Di Fiore Copyright © 2015 Jamshed Iqbal et al. All rights reserved. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors Mon, 02 Mar 2015 11:35:32 +0000 The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (), and lower levels of high density lipoprotein cholesterol (HDL-c) (). The cIMT correlated with levels of anti-CCP (, ), CRP (, ), TNFα (, ), and IL-6 (, ). In multiple regression analysis, cIMT was associated with CRP () and anti-CCP levels (). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. Mónica Vázquez-Del Mercado, Lourdes Nuñez-Atahualpa, Mauricio Figueroa-Sánchez, Eduardo Gómez-Bañuelos, Alberto Daniel Rocha-Muñoz, Beatriz Teresita Martín-Márquez, Esther Guadalupe Corona-Sanchez, Erika Aurora Martínez-García, Héctor Macias-Reyes, Laura Gonzalez-Lopez, Jorge Ivan Gamez-Nava, Rosa Elena Navarro-Hernandez, María Alejandra Nuñez-Atahualpa, and Javier Andrade-Garduño Copyright © 2015 Mónica Vázquez-Del Mercado et al. All rights reserved. Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis Mon, 02 Mar 2015 11:29:41 +0000 Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies. Xia Fan, Zheng Liu, He Jin, Jun Yan, and Hua-ping Liang Copyright © 2015 Xia Fan et al. All rights reserved. Use of a Robotic Device for the Rehabilitation of Severe Upper Limb Paresis in Subacute Stroke: Exploration of Patient/Robot Interactions and the Motor Recovery Process Mon, 02 Mar 2015 11:22:03 +0000 This pioneering observational study explored the interaction between subacute stroke inpatients and a rehabilitation robot during upper limb training. 25 stroke survivors (age years; time since stroke, days) with severe upper limb paresis carried out 16 sessions of robot-assisted shoulder/elbow training (InMotion 2.0, IMT, Inc., MA, USA) combined with standard therapy. The values of 3 patient/robot interaction parameters (a guidance parameter: Stiffness, a velocity-related parameter: Slottime, and Robotic Power) were compared between sessions 1 (S1), 4 (S4), 8 (S8), 12 (S12), and 16 (S16). Pre/post Fugl-Meyer Assessment (FMA) scores were compared in 18 patients. Correlations between interaction parameters and clinical and kinematic outcome measures were evaluated. Slottime decreased at S8 , while Guidance decreased at S12 . Robotic Power tended to decrease until S16. FMA scores improved from S1 to S16 (+49%, ). Changes in FMA score were correlated with the Stiffness parameter (, ). Slottime was correlated with movement velocity. This novel approach demonstrated that a robotic device is a useful and reliable tool for the quantification of interaction parameters. Moreover, changes in these parameters were correlated with clinical and kinematic changes. These results suggested that robot-based recordings can provide new insights into the motor recovery process. Christophe Duret, Ophélie Courtial, Anne-Gaëlle Grosmaire, and Emilie Hutin Copyright © 2015 Christophe Duret et al. All rights reserved. The Epidemiology and Economic Burden of Clostridium difficile Infection in Korea Mon, 02 Mar 2015 11:19:05 +0000 The prevalence of Clostridium difficile infection and the associated burden have recently increased in many countries. While the main risk factors for C. difficile infection include old age and antibiotic use, the prevalence of this infection is increasing in low-risk groups. These trends highlight the need for research on C. difficile infection. This study pointed out the prevalence and economic burden of C. difficile infection and uses the representative national data which is primarily from the database of the Korean Health Insurance Review and Assessment Service, for 2008–2011. The annual economic cost was measured using a prevalence approach, which sums the costs incurred to treat C. difficile infection. C. difficile infection prevalence was estimated to have increased from 1.43 per 100,000 in 2008 to 5.06 per 100,000 in 2011. Moreover, mortality increased from 69 cases in 2008 to 172 in 2011. The economic cost increased concurrently, from $2.4 million in 2008 to $7.6 million, $10.5 million, and $15.8 million in 2009, 2010, and 2011, respectively. The increasing economic burden of C. difficile infection over the course of the study period emphasizes the need for intervention to minimize the burden of a preventable illness like C. difficile infection. Hyung-Yun Choi, So-Youn Park, Young-Ae Kim, Tai-Young Yoon, Joong-Myung Choi, Bong-Keun Choe, So-Hee Ahn, Seok-Jun Yoon, Ye-Rin Lee, and In-Hwan Oh Copyright © 2015 Hyung-Yun Choi et al. All rights reserved. Topical Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated from Opuntia ficus-indica Mon, 02 Mar 2015 11:17:15 +0000 Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO production in vitro (% and %, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (%) equating the indomethacin effects (%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient. Marilena Antunes-Ricardo, Janet A. Gutiérrez-Uribe, Carlos Martínez-Vitela, and Sergio O. Serna-Saldívar Copyright © 2015 Marilena Antunes-Ricardo et al. All rights reserved. Is Visual Registration Equivalent to Semiautomated Registration in Prostate Biopsy? Mon, 02 Mar 2015 10:23:56 +0000 In magnetic resonance iimaging- (MRI-) ultrasound (US) guided biopsy, suspicious lesions are identified on MRI, registered on US, and targeted during biopsy. The registration can be performed either by a human operator (visual registration) or by fusion software. Previous studies showed that software registration is fairly accurate in locating suspicious lesions and helps to improve the cancer detection rate. Here, the performance of visual registration was examined for ability to locate suspicious lesions defined on MRI. This study consists of 45 patients. Two operators with differing levels of experience (1 and 18 years) performed visual registration. The overall spatial difference by the two operators in 72 measurements was 10.6 ± 6.0 mm. Each operator showed a spatial difference of 9.4 ± 5.1 mm (experienced; 39 lesions) and 12.1 ± 6.6 mm (inexperienced; 33 lesions), respectively. In a head-to-head comparison of the same 16 lesions from 12 patients, the spatial differences were 9.7 mm ± 4.9 mm (experienced) and 13.4 mm ± 7.4 mm (inexperienced). There were significant differences between the two operators (unpaired, P value = 0.042; paired, P value = 0.044). The substantial differences by the two operators suggest that visual registration could improperly and inaccurately target many tumors, thereby potentially leading to missed diagnosis or false characterization on pathology. Jin Tae Kwak, Cheng William Hong, Peter A. Pinto, Molly Williams, Sheng Xu, Jochen Kruecker, Pingkun Yan, Baris Turkbey, Peter L. Choyke, and Bradford J. Wood Copyright © 2015 Jin Tae Kwak et al. All rights reserved. Prediction of Drug Indications Based on Chemical Interactions and Chemical Similarities Mon, 02 Mar 2015 09:49:30 +0000 Discovering potential indications of novel or approved drugs is a key step in drug development. Previous computational approaches could be categorized into disease-centric and drug-centric based on the starting point of the issues or small-scaled application and large-scale application according to the diversity of the datasets. Here, a classifier has been constructed to predict the indications of a drug based on the assumption that interactive/associated drugs or drugs with similar structures are more likely to target the same diseases using a large drug indication dataset. To examine the classifier, it was conducted on a dataset with 1,573 drugs retrieved from Comprehensive Medicinal Chemistry database for five times, evaluated by 5-fold cross-validation, yielding five 1st order prediction accuracies that were all approximately 51.48%. Meanwhile, the model yielded an accuracy rate of 50.00% for the 1st order prediction by independent test on a dataset with 32 other drugs in which drug repositioning has been confirmed. Interestingly, some clinically repurposed drug indications that were not included in the datasets are successfully identified by our method. These results suggest that our method may become a useful tool to associate novel molecules with new indications or alternative indications with existing drugs. Guohua Huang, Yin Lu, Changhong Lu, Mingyue Zheng, and Yu-Dong Cai Copyright © 2015 Guohua Huang et al. All rights reserved. Protective and Curative Effects of the Sea Cucumber Holothuria atra Extract against DMBA-Induced Hepatorenal Diseases in Rats Mon, 02 Mar 2015 09:18:29 +0000 Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy of Holothuria atra extract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided into five subgroups pre- or posttreated either with distilled water (DMBA subgroups) or with HaE (200 mg/kg body weight) for seven and fourteen days. Single oral administration of DMBA (15 mg/kg body weight) to Wistar rats resulted in a significant increase in the serum liver enzymes and kidney function’s parameters. DMBA increased level of liver malondialdehyde (MDA), decreased levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) in the liver tissue, and induced liver histopathological alterations. Pre- or posttreatment with HaE orally for 14 days significantly reversed the hepatorenal alterations induced following DMBA administration. In conclusion, HaE exhibits good hepatoprotective, curative, and antioxidant potential against DMBA-induced hepatorenal dysfunction in rats that might be due to decreased free radical generation. Ahmed I. Dakrory, Sohair R. Fahmy, Amel M. Soliman, Ayman S. Mohamed, and Sayed A. M. Amer Copyright © 2015 Ahmed I. Dakrory et al. All rights reserved. Inhibitory and Apoptosis-Inducing Effects of Newcastle Disease Virus Strain AF2240 on Mammary Carcinoma Cell Line Mon, 02 Mar 2015 09:17:33 +0000 Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner. Umar Ahmad, Ismaila Ahmed, Yong Yoke Keong, Nizar Abd Manan, and Fauziah Othman Copyright © 2015 Umar Ahmad et al. All rights reserved. Morphological Study of the Lingula in Adult Human Mandibles of Brazilians Individuals and Clinical Implications Mon, 02 Mar 2015 09:08:13 +0000 Objectives. The purpose of this research was to study, in macerated adult human mandibles, the height of the lingula and provide morphometric data for its location considering aspects such as shape of the lingula, gender, and race. Material and Methods. 132 macerated mandibles of Brazilian adult individuals, both sexes, Amerindian and Caucasian, were used. The distances: from mandibular notch to lingula; from anterior margin of ramus of mandible to lingula; from posterior margin of ramus of mandible to lingula; from mandibular base to lingula, and the height of lingula were obtained. To perform these measurements we used a digital caliper. The variables such as gender and race were analyzed. Results. The mean values found for the height of lingula and its location were determined according to the gender, race, and the lingula shape. Conclusion. This research provides additional data on height of the lingula and morphometric data for its location considering aspects such as shape of the lingula, gender, and race, information that had not been reported in the literature to date. We emphasize that a careful study considering gender and ethnic group makes procedures involving the region of lingula safer. Nilton Alves and Naira Figueiredo Deana Copyright © 2015 Nilton Alves and Naira Figueiredo Deana. All rights reserved. Recent Development in Production and Biotechnological Application of Microbial Enzymes Mon, 02 Mar 2015 08:30:26 +0000 Noomen Hmidet, Neelu Nawani, and Sofiane Ghorbel Copyright © 2015 Noomen Hmidet et al. All rights reserved.