BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. A New Method for Feedback on the Quality of Chest Compressions during Cardiopulmonary Resuscitation Thu, 28 Aug 2014 15:37:54 +0000 Quality of cardiopulmonary resuscitation (CPR) improves through the use of CPR feedback devices. Most feedback devices integrate the acceleration twice to estimate compression depth. However, they use additional sensors or processing techniques to compensate for large displacement drifts caused by integration. This study introduces an accelerometer-based method that avoids integration by using spectral techniques on short duration acceleration intervals. We used a manikin placed on a hard surface, a sternal triaxial accelerometer, and a photoelectric distance sensor (gold standard). Twenty volunteers provided 60 s of continuous compressions to test various rates (80–140 min−1), depths (3–5 cm), and accelerometer misalignment conditions. A total of 320 records with 35312 compressions were analysed. The global root-mean-square errors in rate and depth were below 1.5 min−1 and 2 mm for analysis intervals between 2 and 5 s. For 3 s analysis intervals the 95% levels of agreement between the method and the gold standard were within −1.64–1.67 min−1 and −1.69–1.72 mm, respectively. Accurate feedback on chest compression rate and depth is feasible applying spectral techniques to the acceleration. The method avoids additional techniques to compensate for the integration displacement drift, improving accuracy, and simplifying current accelerometer-based devices. Digna M. González-Otero, Jesus Ruiz, Sofía Ruiz de Gauna, Unai Irusta, Unai Ayala, and Erik Alonso Copyright © 2014 Digna M. González-Otero et al. All rights reserved. Prospect of Stem Cell Conditioned Medium in Regenerative Medicine Thu, 28 Aug 2014 15:34:52 +0000 Background. Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerative medicine. Objective. To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight into their prospect of application in various diseases. Methods. Systematic review using keywords “stem cell” and “conditioned medium” or “secretome” and “therapy.” Data concerning treated conditions/diseases, type of cell that was cultured, medium and supplements to culture the cells, culture condition, CM processing, growth factors and other secretions that were analyzed, method of application, and outcome were noted, grouped, tabulated, and analyzed. Results. Most of CM using studies showed good results. However, the various CM, even when they were derived from the same kind of cells, were produced by different condition, that is, from different passage, culture medium, and culture condition. The growth factor yields of the various types of cells were available in some studies, and the cell number that was needed to produce CM for one application could be computed. Conclusion. Various stem cell-derived conditioned media were tested on various diseases and mostly showed good results. However, standardized methods of production and validations of their use need to be conducted. Jeanne Pawitan Copyright © 2014 Jeanne Pawitan. All rights reserved. Assessment of Cardiac Sarcoidosis with Advanced Imaging Modalities Thu, 28 Aug 2014 15:28:03 +0000 Sarcoidosis is a chronic systemic disease of unknown etiology that is characterized by the presence of noncaseating epithelioid granulomas, usually in multiple organs. Several studies have shown that sarcoidosis might be the result of an exaggerated granulomatous reaction after exposure to unidentified antigens in genetically susceptible individuals. Cardiac involvement may occur and lead to an adverse outcome: the heart mechanics will be affected and that causes ventricular failure, and the cardiac electrical system will be disrupted and lead to third degree atrioventricular block, malignant ventricular tachycardia, and sudden cardiac death. Thus, early diagnosis and treatment of this potentially devastating disease is critically important. However, sensitive and accurate imaging modalities have not been established. Recent studies have demonstrated the promising potential of cardiac magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) in the diagnosis and assessment of cardiac sarcoidosis (CS). In this review, we discuss the epidemiology, etiology, histological findings, and clinical features of sarcoidosis. We also introduce advanced imaging including 18F-FDG PET and cardiac MRI as more reliable diagnostic modalities for CS. Makoto Orii, Toshio Imanishi, and Takashi Akasaka Copyright © 2014 Makoto Orii et al. All rights reserved. Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance Thu, 28 Aug 2014 15:27:02 +0000 The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, in Saccharomyces cerevisiae, haploid strains defective in the TEL1 gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development. Enea Gino Di Domenico, Elena Romano, Paola Del Porto, and Fiorentina Ascenzioni Copyright © 2014 Enea Gino Di Domenico et al. All rights reserved. A Novel Laccase with Potent Antiproliferative and HIV-1 Reverse Transcriptase Inhibitory Activities from Mycelia of Mushroom Coprinus comatus Thu, 28 Aug 2014 15:26:20 +0000 A novel laccase was isolated and purified from fermentation mycelia of mushroom Coprinus comatus with an isolation procedure including three ion-exchange chromatography steps on DEAE-cellulose, CM-cellulose, and Q-Sepharose and one gel-filtration step by fast protein liquid chromatography on Superdex 75. The purified enzyme was a monomeric protein with a molecular weight of 64 kDa. It possessed a unique N-terminal amino acid sequence of AIGPVADLKV, which has considerably high sequence similarity with that of other fungal laccases, but is different from that of C. comatus laccases reported. The enzyme manifested an optimal pH value of 2.0 and an optimal temperature of 60°C using 2,2′-azinobis(3-ethylbenzothiazolone-6-sulfonic acid) diammonium salt (ABTS) as the substrate. The laccase displayed, at pH 2.0 and 37°C, Km values of 1.59 mM towards ABTS. It potently suppressed proliferation of tumor cell lines HepG2 and MCF7, and inhibited human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) with an IC50 value of 3.46 μM, 4.95 μM, and 5.85 μM, respectively, signifying that it is an antipathogenic protein. Shuang Zhao, Cheng-Bo Rong, Chang Kong, Yu Liu, Feng Xu, Qian-Jiang Miao, Shou-Xian Wang, He-Xiang Wang, and Guo-Qing Zhang Copyright © 2014 Shuang Zhao et al. All rights reserved. Glycoprotein IIb/IIIa and P2Y12 Induction by Oligochitosan Accelerates Platelet Aggregation Thu, 28 Aug 2014 15:26:01 +0000 Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro. Mercy Halleluyah Periayah, Ahmad Sukari Halim, Nik Soriani Yaacob, Arman Zaharil Mat Saad, Abdul Rahim Hussein, Ahmad Hazri Abdul Rashid, and Zanariah Ujang Copyright © 2014 Mercy Halleluyah Periayah et al. All rights reserved. New Described Dermatological Disorders Thu, 28 Aug 2014 15:24:29 +0000 Many advances in dermatology have been made in recent years. In the present review article, newly described disorders from the last six years are presented in detail. We divided these reports into different sections, including syndromes, autoinflammatory diseases, tumors, and unclassified disease. Syndromes included are “circumferential skin creases Kunze type” and “unusual type of pachyonychia congenita or a new syndrome”; autoinflammatory diseases include “chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome,” “pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome,” and “pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome”; tumors include “acquired reactive digital fibroma,” “onychocytic matricoma and onychocytic carcinoma,” “infundibulocystic nail bed squamous cell carcinoma,” and “acral histiocytic nodules”; unclassified disorders include “saurian papulosis,” “symmetrical acrokeratoderma,” “confetti-like macular atrophy,” and “skin spicules,” “erythema papulosa semicircularis recidivans.” Müzeyyen Gönül, Bengu Cevirgen Cemil, Havva Ozge Keseroglu, and Havva Kaya Akis Copyright © 2014 Müzeyyen Gönül et al. All rights reserved. Protective Effect of a Prime-Boost Strategy with the Ts87 Vaccine against Trichinella spiralis Infection in Mice Thu, 28 Aug 2014 15:20:04 +0000 Trichinellosis is a widespread zoonosis primarily caused by Trichinella spiralis. Mucosal immunity is crucial for preventing Trichinella spiralis infection. In our previous study, a DNA vaccine with the Trichinella antigen Ts87 delivered by an attenuated Salmonella typhimurium elicited partial protection against Trichinella spiralis infection in mice. In the current study, to elicit a more robust immune response and develop a potent vaccination strategy against trichinellosis, a heterologous prime-boost vaccination regimen for Ts87 was used in mice and the protective efficacy was evaluated compared to the homologous DNA prime-boost or protein prime-boost immunization alone. The results revealed that the DNA-prime/protein-boost vaccination with Ts87 induced higher levels of both humoral and cellular immune responses. The challenge results showed that mice with the DNA-prime/protein-boost vaccination displayed higher muscle larval reduction than those immunized with DNA prime-boost or protein prime-boost. The results demonstrated that mice vaccinated with Ts87 in a DNA-prime/protein-boost strategy effectively elicited a local IgA response and mixed Th1/Th2 immune response that might be responsible for improved protection against Trichinella spiralis infection. Yuan Gu, Bin Zhan, Yaping Yang, Xiaodi Yang, Xi Zhao, Lei Wang, Jing Yang, Kuo Bi, Yunyun Wang, and Xinping Zhu Copyright © 2014 Yuan Gu et al. All rights reserved. Creatine, L-Carnitine, and ω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle Thu, 28 Aug 2014 15:19:19 +0000 Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases. Giuseppe D’Antona, Seyed Mohammad Nabavi, Piero Micheletti, Arianna Di Lorenzo, Roberto Aquilani, Enzo Nisoli, Mariangela Rondanelli, and Maria Daglia Copyright © 2014 Giuseppe D’Antona et al. All rights reserved. The Mcm2-7 Replicative Helicase: A Promising Chemotherapeutic Target Thu, 28 Aug 2014 15:15:54 +0000 Numerous eukaryotic replication factors have served as chemotherapeutic targets. One replication factor that has largely escaped drug development is the Mcm2-7 replicative helicase. This heterohexameric complex forms the licensing system that assembles the replication machinery at origins during initiation, as well as the catalytic core of the CMG (Cdc45-Mcm2-7-GINS) helicase that unwinds DNA during elongation. Emerging evidence suggests that Mcm2-7 is also part of the replication checkpoint, a quality control system that monitors and responds to DNA damage. As the only replication factor required for both licensing and DNA unwinding, Mcm2-7 is a major cellular regulatory target with likely cancer relevance. Mutations in at least one of the six MCM genes are particularly prevalent in squamous cell carcinomas of the lung, head and neck, and prostrate, and MCM mutations have been shown to cause cancer in mouse models. Moreover various cellular regulatory proteins, including the Rb tumor suppressor family members, bind Mcm2-7 and inhibit its activity. As a preliminary step toward drug development, several small molecule inhibitors that target Mcm2-7 have been recently discovered. Both its structural complexity and essential role at the interface between DNA replication and its regulation make Mcm2-7 a potential chemotherapeutic target. Nicholas E. Simon and Anthony Schwacha Copyright © 2014 Nicholas E. Simon and Anthony Schwacha. All rights reserved. CpG Island Methylator Phenotype and Prognosis of Colorectal Cancer in Northeast China Thu, 28 Aug 2014 15:13:33 +0000 Purpose. To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China. Methods. 282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI). Results. 12.77% (36/282) of patients were CIMP-0, 74.1% (209/282) of patients were CIMP-L, and 13.12% (37/282) of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05–2.46; ). CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19–7.89; ) and CIMP-L (HR = 1.97; 95% CI: 1.11–3.48; ), respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0), CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02–5.24; ). Conclusion. CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients. Xia Li, Fulan Hu, Yibaina Wang, Xiaoping Yao, Zuoming Zhang, Fan Wang, Guizhi Sun, Bin-Bin Cui, Xinshu Dong, and Yashuang Zhao Copyright © 2014 Xia Li et al. All rights reserved. Crystal Structure of a Conserved Hypothetical Protein MJ0927 from Methanocaldococcus jannaschii Reveals a Novel Quaternary Assembly in the Nif3 Family Thu, 28 Aug 2014 15:06:43 +0000 A Nif3 family protein of Methanocaldococcus jannaschii, MJ0927, is highly conserved from bacteria to humans. Although several structures of bacterial Nif3 proteins are known, no structure representing archaeal Nif3 has yet been reported. The crystal structure of Methanocaldococcus jannaschii MJ0927 was determined at 2.47 Å resolution to understand the structural differences between the bacterial and archaeal Nif3 proteins. Intriguingly, MJ0927 is found to adopt an unusual assembly comprising a trimer of dimers that forms a cage-like architecture. Electrophoretic mobility-shift assays indicate that MJ0927 binds to both single-stranded and double-stranded DNA. Structural analysis of MJ0927 reveals a positively charged region that can potentially explain its DNA-binding capability. Taken together, these data suggest that MJ0927 adopts a novel quartenary architecture that could play various DNA-binding roles in Methanocaldococcus jannaschii. Sheng-Chia Chen, Chi-Hung Huang, Chia Shin Yang, Shu-Min Kuan, Ching-Ting Lin, Shan-Ho Chou, and Yeh Chen Copyright © 2014 Sheng-Chia Chen et al. All rights reserved. Motion Freeze for Respiration Motion Correction in PET/CT: A Preliminary Investigation with Lung Cancer Patient Data Thu, 28 Aug 2014 15:05:43 +0000 Purpose. Respiratory motion presents significant challenges for accurate PET/CT. It often introduces apparent increase of lesion size, reduction of measured standardized uptake value (SUV), and the mismatch in PET/CT fusion images. In this study, we developed the motion freeze method to use 100% of the counts collected by recombining the counts acquired from all phases of gated PET data into a single 3D PET data, with correction of respiration by deformable image registration. Methods. Six patients with diagnosis of lung cancer confirmed by oncologists were recruited. PET/CT scans were performed with Discovery STE system. The 4D PET/CT with the Varian real-time position management for respiratory motion tracking was followed by a clinical 3D PET/CT scan procedure in the static mode. Motion freeze applies the deformation matrices calculated by optical flow method to generate a single 3D effective PET image using the data from all the 4D PET phases. Results. The increase in SUV and decrease in tumor size with motion freeze for all lesions compared to the results from 3D and 4D was observed in the preliminary data of lung cancer patients. In addition, motion freeze substantially reduced tumor mismatch between the CT image and the corresponding PET images. Conclusion. Motion freeze integrating 100% of the PET counts has the potential to eliminate the influences induced by respiratory motion in PET data. Tzung-Chi Huang, Kuei-Ting Chou, Yao-Ching Wang, and Geoffrey Zhang Copyright © 2014 Tzung-Chi Huang et al. All rights reserved. Autophagy in Development, Cell Differentiation, and Homeodynamics: From Molecular Mechanisms to Diseases and Pathophysiology Thu, 28 Aug 2014 12:39:18 +0000 Ioannis P. Nezis, Maria I. Vaccaro, Rodney J. Devenish, and Gábor Juhász Copyright © 2014 Ioannis P. Nezis et al. All rights reserved. Differences in Extended-Spectrum Beta-Lactamase Producing Escherichia coli Virulence Factor Genes in the Baltic Sea Region Thu, 28 Aug 2014 12:19:42 +0000 The aim of this study was to compare the prevalence of different virulence factor (VF) genes in extended-spectrum beta-lactamase (ESBL) producing Escherichia coli strains isolated from the Baltic Sea region. A total of 432 strains of phenotypically ESBL positive E. coli were collected from 20 institutions located in Estonia, Latvia, Lithuania, and the region of St. Petersburg in Russia from January to May 2012 and analyzed for phylogenetic group and prevalence of 23 VF genes. The strains were collected from clinical material (urine, blood, wound, and respiratory tract). Bacterial isolates were compared according to phylogenetic group, clinical material, and geographical origin. Most of the VF genes were concentrated within phylogenetic group B2 and/or D. When comparing strains isolated from different countries, it was found that strains originating from Estonia and Latvia belonged mainly to group B2 and strains from Lithuania and Russia mainly to groups B2 and D. The P-fimbrial adhesin gene papEF was more prevalent in Russian strains, colicin gene cvaC in Lithuanian strains, and capsular gene kpsMTII in Latvian strains; serum resistant gene traT was less prevalent in Estonian strains. The regional differences of VF genes remained statistically significant after taking into account the phylogenetic distribution in the countries. Jana Lillo, Kristiine Pai, Arta Balode, Mariia Makarova, Kristi Huik, Siiri Kõljalg, Marina Ivanova, Lidia Kaftyreva, Jolanta Miciuleviciene, Paul Naaber, Kristel Parv, Anastasia Pavelkovich, Tiiu Rööp, Karolin Toompere, Ludmila Suzhaeva, and Epp Sepp Copyright © 2014 Jana Lillo et al. All rights reserved. Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer Thu, 28 Aug 2014 12:14:55 +0000 Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms. Ingrid Garajová, Tessa Y. Le Large, Adam E. Frampton, Christian Rolfo, Johannes Voortman, and Elisa Giovannetti Copyright © 2014 Ingrid Garajová et al. All rights reserved. Clinical Nonlinear Laser Imaging of Human Skin: A Review Thu, 28 Aug 2014 10:55:59 +0000 Nonlinear optical microscopy has the potential of being used in vivo as a noninvasive imaging modality for both epidermal and dermal imaging. This paper reviews the capabilities of nonlinear microscopy as a noninvasive high-resolution tool for clinical skin inspection. In particular, we show that two-photon fluorescence microscopy can be used as a diagnostic tool for characterizing epidermal layers by means of a morphological examination. Additional functional information on the metabolic state of cells can be provided by measuring the fluorescence decay of NADH. This approach allows differentiating epidermal layers having different structural and cytological features and has the potential of diagnosing pathologies in a very early stage. Regarding therapy follow-up, we demonstrate that nonlinear microscopy could be successfully used for monitoring the effect of a treatment. In particular, combined two-photon fluorescence and second-harmonic generation microscopy were used in vivo for monitoring collagen remodeling after microablative fractional laser resurfacing and for quantitatively monitoring psoriasis on the basis of the morphology of epidermal cells and dermal papillae. We believe that the described microscopic modalities could find in the near future a stable place in a clinical dermatological setting for quantitative diagnostic purposes and as a monitoring method for various treatments. Riccardo Cicchi, Dimitrios Kapsokalyvas, and Francesco Saverio Pavone Copyright © 2014 Riccardo Cicchi et al. All rights reserved. Molecular Characterization and Screening for Sheath Blight Resistance Using Malaysian Isolates of Rhizoctonia solani Thu, 28 Aug 2014 09:45:27 +0000 Two field isolates of Rhizoctonia solani were isolated from infected paddy plants in Malaysia. These isolates were verified via ITS-rDNA analysis that yielded ~720 bp products of the ITS1-5.8S-ITS4 region, respectively. The sequenced products showed insertion and substitution incidences which may result in strain diversity and possible variation in disease severity. These strains showed some regional and host-specific relatedness via Maximum Likelihood and further phylogenetic analysis via Maximum Parsimony showed that these strains were closely related to R. solani AG1-1A (with 99-100% identity). Subsequent to strain verification and analysis, these isolates were used in the screening of twenty rice varieties for tolerance or resistance to sheath blight via mycelial plug method where both isolates (1801 and 1802) showed resistance or moderate resistance to Teqing, TETEP, and Jasmine 85. Isolate 1802 was more virulent based on the disease severity index values. This study also showed that the mycelial plug techniques were efficient in providing uniform inoculum and humidity for screening. In addition this study shows that the disease severity index is a better mode of scoring for resistance compared to lesion length. These findings will provide a solid basis for our future breeding and screening activities at the institution. Kalaivani Nadarajah, Nurfarahana Syuhada Omar, Marhamah Md. Rosli, and Ong Shin Tze Copyright © 2014 Kalaivani Nadarajah et al. All rights reserved. Symbiotic Plant Peptides Eliminate Candida albicans Both In Vitro and in an Epithelial Infection Model and Inhibit the Proliferation of Immortalized Human Cells Thu, 28 Aug 2014 09:43:50 +0000 The increasing number of multidrug-resistant microbes now emerging necessitates the identification of novel antimicrobial agents. Plants produce a great variety of antimicrobial peptides including hundreds of small, nodule-specific cysteine-rich NCR peptides that, in the legume Medicago truncatula, govern the differentiation of endosymbiotic nitrogen fixing bacteria and, in vitro, can display potent antibacterial activities. In this study, the potential candidacidal activity of 19 NCR peptides was investigated. Cationic NCR peptides having an isoelectric point above 9 were efficient in killing Candida albicans, one of the most common fungal pathogens of humans. None of the tested NCR peptides were toxic for immortalized human epithelial cells at concentrations that effectively killed the fungus; however, at higher concentrations, some of them inhibited the division of the cells. Furthermore, the cationic peptides successfully inhibited C. albicans induced human epithelial cell death in an in vitro coculture model. These results highlight the therapeutic potential of cationic NCR peptides in the treatment of candidiasis. Lilla Ördögh, Andrea Vörös, István Nagy, Éva Kondorosi, and Attila Kereszt Copyright © 2014 Lilla Ördögh et al. All rights reserved. Relationship between CCR and NT-proBNP in Chinese HF Patients, and Their Correlations with Severity of HF Thu, 28 Aug 2014 09:42:10 +0000 Aim. To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity. Methods and Results. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value. Conclusion. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF. Zhigang Lu, Bo Wang, Yunliang Wang, Xueqing Qian, Wei Zheng, and Meng Wei Copyright © 2014 Zhigang Lu et al. All rights reserved. Inhibition of Peroxisome Proliferator-Activated Receptor Gamma Prevents the Melanogenesis in Murine B16/F10 Melanoma Cells Thu, 28 Aug 2014 09:40:05 +0000 The purpose of this study was to investigate if PPAR plays a role in the melanogenesis. B16/F10 cells were divided into five groups: control, melanin stimulating hormone (-MSH), -MSH+retinol, -MSH+GW9662 (PPAR antagonist), and GW9662. Cells in the control group were cultured in the Dulbecco’s modified Eagle’s medium (DMEM) for 48 hrs. To initiate the melanogenesis, cells in all -MSH groups were cultured in medium containing -MSH (10 nM) for 48 hrs. Cells were treated simultaneously with retinol (5 μM) in the -MSH+retinol group. Instead of retinol, GW9662 (10 μM) was cocultured in the -MSH+GW9662 group. Cells in the final group were cultured in the DMEM with GW9662. All the analyses were carried out 48 hours after treatments. The -MSH was able to increase cell number, melanin production, and the activity of tyrosinase, the limiting enzyme in melanogenesis. These -MSH-induced changes were prevented either by retinol or by GW9662. Further analyses of the activities of antioxidant enzymes including glutathione, catalase, and the superoxide dismutase (SOD) showed that -MSH treatment raised the activity of SOD which was dependent on PPAR level. According to our results, the -MSH-induced melanogenesis was PPAR dependent, which also modulated the expression of SOD. Jiun-Han Chen, Junn-Liang Chang, Pei-Ru Chen, Yun-Ju Chuang, Shih-Tsang Tang, Shwu-Fen Pan, Tzer-Bin Lin, Kang-Hua Chen, and Mei-Jung Chen Copyright © 2014 Jiun-Han Chen et al. All rights reserved. Quinolone-Containing Therapies in the Eradication of Helicobacter pylori Thu, 28 Aug 2014 09:30:25 +0000 Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to “rescue” therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy. Seng-Kee Chuah, Wei-Chen Tai, Chen-Hsiang Lee, Chih-Ming Liang, and Tsung-Hui Hu Copyright © 2014 Seng-Kee Chuah et al. All rights reserved. Traumatic Penile Injury: From Circumcision Injury to Penile Amputation Thu, 28 Aug 2014 08:48:46 +0000 The treatment of external genitalia trauma is diverse according to the nature of trauma and injured anatomic site. The classification of trauma is important to establish a strategy of treatment; however, to date there has been less effort to make a classification for trauma of external genitalia. The classification of external trauma in male could be established by the nature of injury mechanism or anatomic site: accidental versus self-mutilation injury and penis versus penis plus scrotum or perineum. Accidental injury covers large portion of external genitalia trauma because of high prevalence and severity of this disease. The aim of this study is to summarize the mechanism and treatment of the traumatic injury of penis. This study is the first review describing the issue. Jae Heon Kim, Jae Young Park, and Yun Seob Song Copyright © 2014 Jae Heon Kim et al. All rights reserved. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats Thu, 28 Aug 2014 08:41:24 +0000 The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4–8°C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid. Jaleh Varshosaz, Somayeh Taymouri, Abbas Pardakhty, Majid Asadi-Shekaari, and Abodolreza Babaee Copyright © 2014 Jaleh Varshosaz et al. All rights reserved. The Probiotic Bifidobacterium breve B632 Inhibited the Growth of Enterobacteriaceae within Colicky Infant Microbiota Cultures Thu, 28 Aug 2014 08:39:14 +0000 Infant colic is a common gastrointestinal disorder of newborns, mostly related to imbalances in the composition of gut microbiota and particularly to the presence of gas-producing coliforms and to lower levels of Bifidobacteria and Lactobacilli. Probiotics could help to contain this disturbance, with formulations consisting of Lactobacillus strains being the most utilized. In this work, the probiotic strain Bifidobacterium breve B632 that was specifically selected for its ability to inhibit gas-producing coliforms, was challenged against the Enterobacteriaceae within continuous cultures of microbiota from a 2-month-old colicky infant. As confirmed by RAPD-PCR fingerprinting, B. breve B632 persisted in probiotic-supplemented microbiota cultures, accounting for the 64% of Bifidobacteria at the steady state. The probiotic succeeded in inhibiting coliforms, since FISH and qPCR revealed that the amount of Enterobacteriaceae after 18 h of cultivation was 0.42 and 0.44 magnitude orders lower in probiotic-supplemented microbiota cultures than in the control ones. These results support the possibility to move to another level of study, that is, the administration of B. breve B632 to a cohort of colicky newborns, in order to observe the behavior of this strain in vivo and to validate its effect in colic treatment. Marta Simone, Caterina Gozzoli, Andrea Quartieri, Giuseppe Mazzola, Diana Di Gioia, Alberto Amaretti, Stefano Raimondi, and Maddalena Rossi Copyright © 2014 Marta Simone et al. All rights reserved. Possible Use of Bacteriophages Active against Bacillus anthracis and Other B. cereus Group Members in the Face of a Bioterrorism Threat Thu, 28 Aug 2014 08:38:43 +0000 Anthrax is an infectious fatal disease with epidemic potential. Nowadays, bioterrorism using Bacillus anthracis is a real possibility, and thus society needs an effective weapon to neutralize this threat. The pathogen may be easily transmitted to human populations. It is easy to store, transport, and disseminate and may survive for many decades. Recent data strongly support the effectiveness of bacteriophage in treating bacterial diseases. Moreover, it is clear that bacteriophages should be considered a potential incapacitative agent against bioterrorism using bacteria belonging to B. cereus group, especially B. anthracis. Therefore, we have reviewed the possibility of using bacteriophages active against Bacillus anthracis and other species of the B. cereus group in the face of a bioterrorism threat. Ewa Jończyk-Matysiak, Marlena Kłak, Beata Weber-Dąbrowska, Jan Borysowski, and Andrzej Górski Copyright © 2014 Ewa Jończyk-Matysiak et al. All rights reserved. Clinical Features and Molecular Analysis of Hb H Disease in Taiwan Thu, 28 Aug 2014 08:28:53 +0000 Thalassemia is highly prevalent in Taiwan, but limited data are available about the association between genotypes and clinical manifestations in Taiwanese patients with Hb H disease. Here, we studied α-globin gene abnormalities and clinical features in Taiwanese patients with Hb H disease. Of the 90 patients, sixty-four (71.1%) were deletional and twenty-six (28.9%) were nondeletional Hb H disease. The () type of -thalassemia mutation was detected in the majority of patients (>95%). The most common genotype was (), followed by (). After further investigation of the genotype-phenotype correlation in 68 patients, we found that patients with nondeletional Hb H disease had more severe clinical features than those with deletional Hb H disease, including younger age at diagnosis, more requirement of blood transfusions, and larger proportion of patients with splenomegaly, hepatomegaly or jaundice. This is probably a consequence of the lower hemoglobin levels and the higher Hb H levels. The clinical severity was highly variable even among patients with an identical genotype, and the diversity was much more profound among patients with () genotype. Therefore, predicting the phenotype directly from the genotype in Hb H disease remains relatively difficult in Taiwan. Yu-Hua Chao, Kang-Hsi Wu, Han-Ping Wu, Su-Ching Liu, Ching-Tien Peng, and Maw-Sheng Lee Copyright © 2014 Yu-Hua Chao et al. All rights reserved. Noncoding RNAs as Novel Biomarkers in Prostate Cancer Thu, 28 Aug 2014 07:21:42 +0000 Prostate cancer (PCa) is the second most common diagnosed malignant disease in men worldwide. Although serum PSA test dramatically improved the early diagnosis of PCa, it also led to an overdiagnosis and as a consequence to an overtreatment of patients with an indolent disease. New biomarkers for diagnosis, prediction, and monitoring of the disease are needed. These biomarkers would enable the selection of patients with aggressive or progressive disease and, hence, would contribute to the implementation of individualized therapy of the cancer patient. Since the FDA approval of the long noncoding PCA3 RNA-based urine test for the diagnosis of PCa patients, many new noncoding RNAs (ncRNAs) associated with PCa have been discovered. According to their size and function, ncRNAs can be divided into small and long ncRNAs. NcRNAs are expressed in (tumor) tissue, but many are also found in circulating tumor cells and in all body fluids as protein-bound or incorporated in extracellular vesicles. In these protected forms they are stable and so they can be easily analyzed, even in archival specimens. In this review, the authors will focus on ncRNAs as novel biomarker candidates for PCa diagnosis, prediction, prognosis, and monitoring of therapeutic response and discuss their potential for an implementation into clinical practice. C. G. H. Rönnau, G. W. Verhaegh, M. V. Luna-Velez, and J. A. Schalken Copyright © 2014 C. G. H. Rönnau et al. All rights reserved. Radiofrequency Thermoablation of HCC Larger Than 3 cm and Less Than 5 cm Proximal to the Gallbladder without Gallbladder Isolation: A Single Center Experience Thu, 28 Aug 2014 07:04:08 +0000 Radiofrequency ablation (RFA) is an effective minimally invasive treatment for nonsurgical hepatocellular carcinoma (HCC), but ablation of tumors close to the gallbladder could be associated with several complications. We report our experience on the treatment of HCC close to the gallbladder with RFA. Eight RFA procedures were performed in eight patients with HCC larger than 3 cm and less than 5 cm close to the gallbladder. In all cases, a percutaneous approach was used. There were no major complications. Only in two patients a minimal wall thickening of the gallbladder was observed. Contrast enhanced computed tomography carried out after 30 days from the first procedure showed complete necrosis in seven patients (87%). Only one patient had local recurrence at 11 months of followup. Although limited, our experience suggests that, after careful preprocedural planning, in experienced hands and with appropriate technology, percutaneous RFA could be safely performed even for lesions larger than 3 cm located in close adjacency to the gallbladder. Antonio Orlacchio, Fabrizio Chegai, Costantino Del Giudice, Mariangela Massaccesi, Elisa Costanzo, Elena Di Caprera, and Giovanni Simonetti Copyright © 2014 Antonio Orlacchio et al. All rights reserved. Diethylstilbestrol Exposure in Neonatal Mice Induces Changes in the Adulthood in the Immune Response to Taenia crassiceps without Modifications of Parasite Loads Thu, 28 Aug 2014 06:31:45 +0000 Industrial growth has increased the exposition to endocrine disruptor compounds (EDC’s), which are exogenous agents with agonist or antagonist action of endogenous steroid hormones that may affect the course of parasite infections. We wanted to determine if the exposure to diethylstilbestrol (DES), an estrogen agonist, to both male and female mice affected the immune response and their susceptibility to T. crassiceps cysticercosis. In all infected groups, females showed higher parasite loads than males, and neonatal DES administration did not modify this pattern. In the spleen, noninfected mice showed sex-related differences in the percentage of the CD8+ subpopulation, but DES decreased the percentage of CD3+, CD19+, and CD8+ subpopulations in infected mice. In the mesenteric lymphatic node (MNL), DES showed a dimorphic effect in the percentage of CD19+ cells. Regarding estrogen receptor alpha (ER-α) expression, DES treatment induced a reduction in the expression of this receptor in both noninfected female and male mice in the spleen, which was decreased only in males in CD3+ and CD8+ lymphocytes in MNL cell subpopulations. Our study is the first one to demonstrate that DES neonatal treatment in male and female mice affects the immune cell percentage, without effect on the susceptibility to T. crassiceps cysticercosis. Karen E. Nava-Castro, Jorge Morales-Montor, Alejandra Ortega-Hernando, and Ignacio Camacho-Arroyo Copyright © 2014 Karen E. Nava-Castro et al. All rights reserved.