BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. The Effects of Educational Campaigns and Smoking Bans in Public Places on Smokers’ Intention to Quit Smoking: Findings from 17 Cities in China Mon, 04 May 2015 07:01:22 +0000 Despite the perceived success of educational campaigns and smoking bans in public places in China, the actual effects have not been investigated. This study examines the effects of the two policies by major characteristics of smokers and whether the affected smokers have intention to quit smoking. A cross-sectional survey was conducted in 17 cities in China and 16,616 participants were selected using multistage stratified sampling. Logistic regression models were used to examine the effects of educational campaigns and smoking bans in public places on their intention to quit smoking. Results show that the Chinese government should try every means to build its tobacco control publicity and implement various forms of public educational campaigns to enhance smokers’ knowledge of the health consequences of smoking. In addition, China should emphasize the enforcement of the existing smoking prohibitions and regulations by implementing local tobacco control legislation and total prohibitions in all public places and workplaces. Biao Luo, Liang Wan, Liang Liang, and Tieshan Li Copyright © 2015 Biao Luo et al. All rights reserved. Emergence of Carbapenem-Resistant Klebsiella pneumoniae: Progressive Spread and Four-Year Period of Observation in a Cardiac Surgery Division Mon, 04 May 2015 06:18:43 +0000 Frequent use of carbapenems has contributed to the increase to K. pneumoniae strains resistant to this class of antibiotics (CRKP), causing a problem in the clinical treatment of patients. This investigation reports the epidemiology, genetic diversity, and clinical implication of the resistance to drugs mediated by CRKP in our hospital. A total of 280 K. pneumoniae strains were collected; in particular 98/280 (35%) were CRKP. Sequencing analysis of CRKP isolated strains showed that 9/98 of MBL-producing strains carried the gene and 89/98 of the isolates were positive for . Antimicrobial susceptibility tests revealed a complete resistance to third-generation cephalosporins and a moderate resistance to tigecycline, gentamicin, and fluoroquinolones with percentages of resistance of 61%, 64%, and 98%, respectively. A resistance of 31% was shown towards trimethoprim-sulfamethoxazole. Colistin was the most active agent against CRKP with 99% of susceptibility. Clonality was evaluated by PFGE and MLST: MLST showed the same clonal type, ST258, while PFGE analysis indicated the presence of a major clone, namely, pulsotype A. This finding indicates that the prevalent resistant isolates were genetically related, suggesting that the spread of these genes could be due to clonal dissemination as well as to genetic exchange between different clones. Fortunata Lombardi, Paola Gaia, Rea Valaperta, Maria Cornetta, Milvana Rosa Tejada, Luca Di Girolamo, Alessandra Moroni, Federica Ramundo, Alessio Colombo, Massimiliano Valisi, and Elena Costa Copyright © 2015 Fortunata Lombardi et al. All rights reserved. Antimicrobial Resistance Profile and Genotypic Characteristics of Streptococcus suis Capsular Type 2 Isolated from Clinical Carrier Sows and Diseased Pigs in China Mon, 04 May 2015 06:18:11 +0000 Streptococcus suis serotype 2 is an important zoonotic pathogen. Antimicrobial resistance phenotypes and genotypic characterizations of S. suis 2 from carrier sows and diseased pigs remain largely unknown. In this study, 96 swine S. suis type 2, 62 from healthy sows and 34 from diseased pigs, were analyzed. High frequency of tetracycline resistance was observed, followed by sulfonamides. The lowest resistance of S. suis 2 for β-lactams supports their use as the primary antibiotics to treat the infection of serotype 2. In contrast, 35 of 37 S. suis 2 with ML phenotypes were isolated from healthy sows, mostly encoded by the ermB and/or the mefA genes. Significantly lower frequency of mrp+/epf+/sly+ was observed among serotype 2 from healthy sows compared to those from diseased pigs. Furthermore, isolates from diseased pigs showed more homogeneously genetic patterns, with most of them clustered in pulsotypes A and E. The data indicate the genetic complexity of S. suis 2 between herds and a close linkage among isolates from healthy sows and diseased pigs. Moreover, many factors, such as extensive use of tetracycline or diffusion of Tn916 with tetM, might have favored for the pathogenicity and widespread dissemination of S. suis serotype 2. Chunping Zhang, Zhongqiu Zhang, Li Song, Xuezheng Fan, Fang Wen, Shixin Xu, and Yibao Ning Copyright © 2015 Chunping Zhang et al. All rights reserved. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels Sun, 03 May 2015 15:24:21 +0000 The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation. Md. Ibrahim Khalil, E. M. Tanvir, Rizwana Afroz, Siti Amrah Sulaiman, and Siew Hua Gan Copyright © 2015 Md. Ibrahim Khalil et al. All rights reserved. In Vitro Activity of Imipenem and Colistin against a Carbapenem-Resistant Klebsiella pneumoniae Isolate Coproducing SHV-31, CMY-2, and DHA-1 Sun, 03 May 2015 15:23:46 +0000 We investigated the synergism of colistin and imipenem against a multidrug-resistant K. pneumoniae isolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the common β-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. The , , and were detected. Outer membrane porin genes analysis revealed loss of ompK36 and frame-shift mutation of ompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L) and 1x MIC of imipenem (8 mg/L) was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistant K. pneumoniae infections. Hung-Jen Tang, Yee-Huang Ku, Mei-Feng Lee, Yin-Ching Chuang, and Wen-Liang Yu Copyright © 2015 Hung-Jen Tang et al. All rights reserved. Nonalcoholic Steatohepatitis: A Search for Factual Animal Models Sun, 03 May 2015 14:28:26 +0000 Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, which occurs in the absence of alcohol abuse. NAFLD can evolve into progressive liver injury and fibrosis in the form of nonalcoholic steatohepatitis (NASH). Several animal models have been developed to attempt to represent the morphological, biochemical, and clinical features of human NASH. The actual review presents a critical analysis of the most commonly used experimental models of NAFLD/NASH development. These models can be classified into genetic, nutritional, and a combination of genetic and nutritional factors. The main genetic models are ob/ob and db/db mutant mice and Zucker rats. The principal nutritional models employ methionine- and choline-deficient, high-fat, high-cholesterol and high-cholate, cafeteria, and high-fructose diets. Currently, associations between high-fructose and various compositions of high-fat diets have been widely studied. Previous studies have encountered significant difficulties in developing animal models capable of reproducing human NASH. Some models produce consistent morphological findings, but the induction method differs significantly compared with the pathophysiology of human NASH. Other models precisely represent the clinical and etiological contexts of this disease but fail to provide accurate histopathological representations mainly in the progression from steatosis to liver fibrosis. Sheila Cristina L. Sanches, Leandra Naira Z. Ramalho, Marlei Josiele Augusto, Deisy Mara da Silva, and Fernando Silva Ramalho Copyright © 2015 Sheila Cristina L. Sanches et al. All rights reserved. Khat Use: What Is the Problem and What Can Be Done? Sun, 03 May 2015 14:20:50 +0000 The chewing of khat leaves is an established tradition in East Africa but is much less prevalent in other areas of the world and is mostly limited to Somali communities. However, our understanding of what constitutes problematic khat use in the Somali community in Victoria, Australia, is limited. The objectives of this study were to better understand the views of Somali community representatives and primary care practitioners regarding problematic khat use, to consider relevant harm minimisation strategies, and to develop resources to assist individuals with problematic khat use and their families. Qualitative research methods were used to investigate the experiences and perceptions of khat use among Somalis and mainstream primary care practitioners. Six focus groups were conducted with 37 members of the Somali community and 11 primary care practitioners. Thematic analysis was used to analyse transcripts. Various indicators of the problematic use of khat were identified, including adverse physical and mental health effects, social isolation, family breakdown, and neglect of social responsibilities. Potential harm minimisation strategies were identified including the adoption of health promotion through education, outreach to the community, and the use of universal harm minimisation strategies specifically tailored to khat use. Yusuf Sheikh Omar, Anna Jenkins, Marieke van Regteren Altena, Harvey Tuck, Chris Hynan, Ahmed Tohow, Prem Chopra, and David Castle Copyright © 2015 Yusuf Sheikh Omar et al. All rights reserved. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage Sun, 03 May 2015 14:13:28 +0000 Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD. Georgios Liappas, Guadalupe Tirma Gónzalez-Mateo, Pedro Majano, José Antonio Sánchez- Tomero, Marta Ruiz-Ortega, Raquel Rodrigues Díez, Pilar Martín, Raquel Sanchez-Díaz, Rafael Selgas, Manuel López-Cabrera, and Abelardo Aguilera Peralta Copyright © 2015 Georgios Liappas et al. All rights reserved. Epidemiological Characterization of Drug Resistance among Mycobacterium tuberculosis Isolated from Patients in Northeast of Iran during 2012-2013 Sun, 03 May 2015 14:08:31 +0000 Introduction. Tuberculosis is still one of the most important health problems in developing countries and increasing drug resistance is the main concern for its treatment. This study was designed to characterize the drug resistant Mycobacterium tuberculosis isolated from patients suffering from pulmonary tuberculosis in northeast of Iran. Method. In this cross-sectional study during 2012-2013, drug susceptibility testing was performed on Mycobacterium tuberculosis isolated in northeast of Iran using proportional method. Epidemiological data concerning these strains were also analyzed. Results. Among 125 studied isolates, 25 mycobacteria (20%) were diagnosed as nontuberculosis mycobacteria. Among the remaining 100 Mycobacterium tuberculosis isolates, the resistance rates were 7%, 7%, 3%, and 9% against isoniazid, rifampin, ethambutol, and streptomycin, respectively. Four isolates were resistant against both isoniazid and rifampin (MDR tuberculosis). The highest resistance rate was observed among 15–45-year-old patients. The MDR tuberculosis was much more prevalent among those who had previous history of treatment. Conclusion. Considering these findings, DOTS strategy should be emphasized and promptly used in order to prevent further resistance. Regarding the high rate of nontuberculosis mycobacteria, it is recommended that confirmatory tests were performed before any therapeutic decision. Ashraf Tavanaee Sani, Abolfazl Shakiba, Maryam Salehi, Hamid Reza Bahrami Taghanaki, Seiedeh Fatemeh Ayati Fard, and Kiarash Ghazvini Copyright © 2015 Ashraf Tavanaee Sani et al. All rights reserved. Zebrafish as a Model for the Study of Human Myeloid Malignancies Sun, 03 May 2015 14:08:05 +0000 Myeloid malignancies are heterogeneous disorders characterized by uncontrolled proliferation or/and blockage of differentiation of myeloid progenitor cells. Although a substantial number of gene alterations have been identified, the mechanism by which these abnormalities interact has yet to be elucidated. Over the past decades, zebrafish have become an important model organism, especially in biomedical research. Several zebrafish models have been developed to recapitulate the characteristics of specific myeloid malignancies that provide novel insight into the pathogenesis of these diseases and allow the evaluation of novel small molecule drugs. This report will focus on illustrative examples of applications of zebrafish models, including transgenesis, zebrafish xenograft models, and cell transplantation approaches, to the study of human myeloid malignancies. Jeng-Wei Lu, Meng-Shan Hsieh, Heng-An Liao, Yi-Ju Yang, Yi-Jung Ho, and Liang-In Lin Copyright © 2015 Jeng-Wei Lu et al. All rights reserved. Pain Control after Total Knee Arthroplasty: Comparing Intra-Articular Local Anesthetic Injection with Femoral Nerve Block Sun, 03 May 2015 13:09:34 +0000 Background. Direct intra-articular injection of low doses of local anesthetic (IALA) after closure of the joint capsule remains controversial for pain control after total knee arthroplasty (TKA). Methods. A retrospective study comparing patients receiving IALA with high doses (0.5% bupivacaine 60 mL) of local anesthetics or FNB in addition to intravenous patient-controlled analgesia with opioids for pain management after TKA was conducted. The primary end point was to compare the analgesic efficacy and early ambulation between the two groups. Results. No significant differences between the two groups in pain intensity, cumulative opioid consumption, incidences of opioid-related side effects, the time interval from the end of operation to the first time the patient could walk assisted with a walker postoperatively, and postoperative hospital stay were identified. Three patients in the IALA group but none in the FNB group walked within 12 hours after the end of operation. Summary. IALA with high doses of local anesthetics provides comparable analgesic efficacy as single-shot FNB after TKA and might be associated with earlier ambulation than FNB postoperatively. Shengchin Kao, Hungchen Lee, Chihwen Cheng, Chingfeng Lin, and Hsini Tsai Copyright © 2015 Shengchin Kao et al. All rights reserved. Population Structure and Oxacillin Resistance of Staphylococcus aureus from Pigs and Pork Meat in South-West of Poland Sun, 03 May 2015 13:03:12 +0000 The genotypes and oxacillin resistance of 420 S. aureus isolates from pigs () and pork () were analyzed. Among 18 spa types detected in S. aureus from pig t011, t021, t034, t091, t318, t337, and t1334 were the most frequent. Among 30 spa types found in S. aureus isolates from pork t084, t091, t499, t4309, t12954, and t13074 were dominant. The animal S. aureus isolates were clustered into MLST clonal complexes CC7, CC9, CC15, CC30, and CC398 and meat-derived isolates to CC1, CC7, and CC15. Thirty-six MRSA were isolated exclusively from pigs. All MRSA were classified to spa t011 SCCmecV. BORSA phenotype was found in 14% S. aureus isolates from pigs and 10% isolates from pork meat. spa t034 dominated among BORSA from pigs and t091 among meat-derived BORSA. This is the first report on spa types and oxacillin resistance of S. aureus strains from pigs and pork meat in Poland. Besides S. aureus CC9, CC30, and CC398 known to be distributed in pigs, the occurrence of genotype belonging to CC7 in this species has been reported for the first time. To our knowledge it is also the first report concerning CC398 BORSA isolates from pigs and pork meat. Paweł Krupa, Jarosław Bystroń, Magdalena Podkowik, Joanna Empel, Aneta Mroczkowska, and Jacek Bania Copyright © 2015 Paweł Krupa et al. All rights reserved. Distention of the Immature Left Ventricle Triggers Development of Endocardial Fibroelastosis: An Animal Model of Endocardial Fibroelastosis Introducing Morphopathological Features of Evolving Fetal Hypoplastic Left Heart Syndrome Sun, 03 May 2015 12:56:22 +0000 Background. Endocardial fibroelastosis (EFE), characterized by a diffuse endocardial thickening through collagen and elastin fibers, develops in the human fetal heart restricting growth of the left ventricle (LV). Recent advances in fetal imaging indicate that EFE development is directly associated with a distended, poorly contractile LV in evolving hypoplastic left heart syndrome (HLHS). In this study, we developed an animal model of EFE by introducing this human fetal LV morphopathology to an immature rat heart. Methods and Results. A neonatal donor heart, in which aortic regurgitation (AR) was created, was heterotopically transplanted into a recipient adult rat. AR successfully induced the LV morphology of evolving HLHS in the transplanted donor hearts, which resulted in the development of significant EFE covering the entire LV cavity within two weeks postoperatively. In contrast, posttransplants with a competent aortic valve displayed unloaded LVs with a trace of EFE. Conclusions. We could show that distention of the immature LV in combination with stagnant flow triggers EFE development in this animal model. This model would serve as a robust tool to develop therapeutic strategies to treat EFE while providing insight into its pathogenesis. Shogo Shimada, Christian Robles, Ben M. W. Illigens, Alejandra M. Casar Berazaluce, Pedro J. del Nido, and Ingeborg Friehs Copyright © 2015 Shogo Shimada et al. All rights reserved. An Activity of Thioacyl Derivatives of 4-Aminoquinolinium Salts towards Biofilm Producing and Planktonic Forms of Coagulase-Negative Staphylococci Sun, 03 May 2015 12:54:57 +0000 Microorganisms present in different environments have developed specific mechanisms of settling on various abiotic and biotic surfaces by forming a biofilm. It seems to be well justified to search for new compounds enabling biofilm reduction, which is highly resistant to antibiotics. This study was thus an initial assessment of the antibacterial activity of two new quinoline derivatives of a structure of 3-thioacyl 1-methyl 4-arylaminoquinolinium salts against coagulase-negative staphylococci (CoNS) isolated from a hospital environment, in a form of both biofilms and in planktonic form. Thirty-three stains of CoNS isolated from the hospital environment (air, surfaces) and seven reference strains from the ATCC collection were selected for the study. The mean MIC value for 1-methyl-3-benzoylthio-4-(4-chlorophenylamino)quinolinum chloride (4-chlorophenylamino derivative) was 42.60 ± 19.91 μg/mL, and in the case of strains subjected to 1-methyl-3-benzoylthio-4-(4-fluorophenylamino)quinolinum chloride (4-fluorophenylamino derivative) activity, the mean MIC value was 43.20 ± 14.30 μg/mL. The mean concentration of 4-chlorophenylamino derivative that inhibited biofilm formation was 86.18 ± 30.64 μg/mL. The mean concentration of 4-fluorophenylamino derivatives that inhibited biofilm formation was higher and amounted to 237.09 ± 160.57 μg/mL. Based on the results, both derivatives of the examined compounds exhibit high antimicrobial activity towards strains growing both in planktonic and biofilm form. Robert D. Wojtyczka, Andrzej Zięba, Arkadiusz Dziedzic, Małgorzata Kępa, and Danuta Idzik Copyright © 2015 Robert D. Wojtyczka et al. All rights reserved. Manifestation of Hyperandrogenism in the Continuous Light Exposure-Induced PCOS Rat Model Sun, 03 May 2015 12:43:48 +0000 Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and its pathogenesis has yet to be completely clarified. A fully convincing animal model has not been established for PCOS. In earlier studies, researchers have shown that the exposure of rats to continuous light can induce PCOS; nevertheless, hyperandrogenism, a key characteristic observed in human PCOS, has not been reported previously. In the present study, we found that (1) body weights decreased in female rats in a continuous light environment with both ovarian and uterine augmentation; (2) the estrous cycle in rats under continuous light environment was disordered, and polycystic ovary-like changes occurred, accompanied with fur loss and lethargy; and (3) serum testosterone levels in rats in a continuous light environment significantly increased. Our data suggest that continuous light can lead to the occurrence of PCOS in female rats without the need for drugs; this is a reasonable PCOS animal model that is more consistent with the natural disease state in humans; and poor sleep habits or negligence of sleep hygiene may be an important lifestyle factor in pathogenesis of PCOS. Xuezhi Kang, Lina Jia, and Xueyong Shen Copyright © 2015 Xuezhi Kang et al. All rights reserved. Morphological and Biomechanical Differences in the Elastase and AngII apoE−/− Rodent Models of Abdominal Aortic Aneurysms Sun, 03 May 2015 12:39:28 +0000 An abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals) have been developed to study the disease during its initiation and progression. To date, most studies have used ex vivo methods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence from in vivo ultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngII apoE−/− mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments. Evan H. Phillips, Alexa A. Yrineo, Hilary D. Schroeder, Katherine E. Wilson, Ji-Xin Cheng, and Craig J. Goergen Copyright © 2015 Evan H. Phillips et al. All rights reserved. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate Sun, 03 May 2015 12:35:47 +0000 Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. João P. Costa-Nunes, Brandon H. Cline, Margarida Araújo-Correia, Andreia Valença, Natalyia Markova, Oleg Dolgov, Aslan Kubatiev, Naira Yeritsyan, Harry W. M. Steinbusch, and Tatyana Strekalova Copyright © 2015 João P. Costa-Nunes et al. All rights reserved. The TF-miRNA Coregulation Network in Oral Lichen Planus Sun, 03 May 2015 12:33:38 +0000 Oral lichen planus (OLP) is a chronic inflammatory disease that affects oral mucosa, some of which may finally develop into oral squamous cell carcinoma. Therefore, pinpointing the molecular mechanisms underlying the pathogenesis of OLP is important to develop efficient treatments for OLP. Recently, the accumulation of the large amount of omics data, especially transcriptome data, provides opportunities to investigate OLPs from a systematic perspective. In this paper, assuming that the OLP associated genes have functional relationships, we present a new approach to identify OLP related gene modules from gene regulatory networks. In particular, we find that the gene modules regulated by both transcription factors (TFs) and microRNAs (miRNAs) play important roles in the pathogenesis of OLP and many genes in the modules have been reported to be related to OLP in the literature. Yu-Ling Zuo, Di-Ping Gong, Bi-Ze Li, Juan Zhao, Ling-Yue Zhou, Fang-Yang Shao, Zhao Jin, and Yuan He Copyright © 2015 Yu-Ling Zuo et al. All rights reserved. Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease Sun, 03 May 2015 12:24:25 +0000 A hopeful spinal cord repairing strategy involves the activation of neural precursor cells. Unfortunately, their ability to generate neurons after injury appears limited. Another process promoting functional recovery is synaptic plasticity. We have previously studied some mechanisms of spinal plasticity involving BDNF, Shh, Notch-1, Numb, and Noggin, by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin. TDP-43 is a nuclear RNA/DNA binding protein involved in amyotrophic lateral sclerosis. Interestingly, TDP-43 could be localized at the synapse and affect synaptic strength. Here, we would like to deepen the investigation of this model of spinal plasticity. After lesion, we observed a glial reaction and an activity-dependent modification of Shh, Noggin, and Numb proteins. By using multivariate regression models, we found that Shh and Noggin could affect motor performance and that these proteins could be associated with both TDP-43 and Numb. Our data suggest that TDP-43 is likely an important regulator of synaptic plasticity, probably in collaboration with other proteins involved in both neurogenesis and synaptic plasticity. Moreover, given the rapidly increasing knowledge about spinal cord plasticity, we believe that further efforts to achieve spinal cord repair by stimulating the intrinsic potential of spinal cord will produce interesting results. Rosario Gulino, Rosalba Parenti, and Massimo Gulisano Copyright © 2015 Rosario Gulino et al. All rights reserved. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection Sun, 03 May 2015 12:22:12 +0000 Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. Elena Ufimtseva Copyright © 2015 Elena Ufimtseva. All rights reserved. Occurrence of Multidrug Resistant Extended Spectrum Beta-Lactamase-Producing Bacteria on Iceberg Lettuce Retailed for Human Consumption Sun, 03 May 2015 12:21:20 +0000 Antibiotic resistance in bacteria is a global problem exacerbated by the dissemination of resistant bacteria via uncooked food, such as green leafy vegetables. New strains of bacteria are emerging on a daily basis with novel expanded antibiotic resistance profiles. In this pilot study, we examined the occurrence of antibiotic resistant bacteria against five classes of antibiotics on iceberg lettuce retailed in local convenience stores in Rochester, Michigan. In this study, 138 morphologically distinct bacterial colonies from 9 iceberg lettuce samples were randomly picked and tested for antibiotic resistance. Among these isolates, the vast majority (86%) demonstrated resistance to cefotaxime, and among the resistant bacteria, the majority showed multiple drug resistance, particularly against cefotaxime, chloramphenicol, and tetracycline. Three bacterial isolates (2.17%) out of 138 were extended spectrum beta-lactamase (ESBL) producers. Two ESBL producers (T1 and T5) were identified as Klebsiella pneumoniae, an opportunistic pathogen with transferable sulfhydryl variable- (SHV-) and TEM-type ESBLs, respectively. The DNA sequence analysis of the detected in K. pneumoniae isolate T1 revealed 99% relatedness to genes found in clinical isolates. This implies that iceberg lettuce is a potential reservoir of newly emerging and evolving antibiotic resistant bacteria and its consumption poses serious threat to human health. Natasha Bhutani, Chithra Muraleedharan, Deepa Talreja, Sonia Walia Rana, Sandeep Walia, Ashok Kumar, and Satish K. Walia Copyright © 2015 Natasha Bhutani et al. All rights reserved. Osteoarticular Expression of Musashi-1 in an Experimental Model of Arthritis Sun, 03 May 2015 12:20:04 +0000 Background. Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating the maintenance and differentiation of stem/precursor cells. The objectives of this investigation were to perform a morphological study of the experimental CIA model, evaluate the effect of TNFα-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. Methods. CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. Results. Clinically, TNFα-blocker treatment attenuated CIA on day 32 after immunization (). Msi1 protein expression was significantly higher in joints damaged by CIA than in those with no lesions () and was related to the severity of the lesions (Spearman’s rho = 0.775, ). Conclusions. Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair. Francisco O’Valle, Magdalena Peregrina, Vicente Crespo-Lora, Pablo Galindo-Moreno, Maria Roman, Miguel Padial-Molina, Francisco Mesa, Jose Aneiros-Fernandez, David Aguilar, Elena Gonzalez-Rey, Mario Delgado, and Pedro Hernandez-Cortes Copyright © 2015 Francisco O’Valle et al. All rights reserved. Attention Deficit Hyperactivity Disorder Symptoms, Comorbidities, Substance Use, and Social Outcomes among Men and Women in a Canadian Sample Sun, 03 May 2015 12:17:49 +0000 Background. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that can persist in adolescence and adulthood. Aim. To examine prevalence of ADHD symptoms and correlates in a representative sample of adults 18 years and older living in Ontario, Canada. Method. We used the Centre for Addiction and Mental Health Monitor, an ongoing cross-sectional telephone survey, to examine the relationships between ADHD positive symptoms and comorbidities, substance use, medication use, social outcomes, and sociodemographics. Results. Of 4014 residents sampled in 2011-2012, 3.30% (2.75%–3.85%) screened positively for ADHD symptoms (women = 3.6%; men = 3.0%). For men, distress, antisocial symptoms, cocaine use, antianxiety medication use, antidepressant medication use, and criminal offence arrest were associated with positive ADHD screen. For women, distress, cocaine use, antianxiety medication use, antidepressant medication use, pain medication use, and motor vehicle collision in the past year were associated with positive ADHD screen. Conclusions. ADHD symptoms are associated with adverse medical and social outcomes that are in some cases gender specific. Evelyn Vingilis, Patricia G. Erickson, Maggie E. Toplak, Nathan J. Kolla, Robert E. Mann, Jane Seeley, Mark vanderMaas, and Deanne S. Daigle Copyright © 2015 Evelyn Vingilis et al. All rights reserved. Layer 5 Pyramidal Neurons’ Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis Sun, 03 May 2015 12:16:00 +0000 This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. Diana Urrego, Julieta Troncoso, and Alejandro Múnera Copyright © 2015 Diana Urrego et al. All rights reserved. Discrepancies in Drug Susceptibility Test for Tuberculosis Patients Resulted from the Mixed Infection and the Testing System Sun, 03 May 2015 12:08:30 +0000 To find the potential reasons for the discrepancies in the drug susceptibility test (DST) of M. tuberculosis isolates, twenty paired isolates with disputed drug susceptibilities to isoniazid (INH) were selected according to the MGIT960 testing and Löwenstein-Jensen (L-J) proportion methods. Their MICs were confirmed again by broth microdilution method and by L-J proportion method. The spoligotyping results showed that, of all the 20 paired strains, 11 paired isolates belonged to the Beijing genotype and 6 paired isolates belonged to SIT1634, and that each of the remaining 3 paired isolates had two genotypes, namely, SIT1 and SIT1634. Those 3 paired isolates with different intrapair spoligotypes were further confirmed as mixed infection by the results that those three pairs of isolates with different 12 locus MIRU intrapair types and one pair carried different base pair at codon 315 (AGC versus AAC). Totally mutations in the katG gene were identified in 13 paired isolates. No mutations were found in the regulatory sequences and open reading frames (ORF) of the inhA and ahpC genes in any of the tested isolates. Those results showed that the different test systems and the mixed infection with particular genotypes of M. tuberculosis strains contributed to the drug susceptibility discrepancies. Zaoxian Mei, Zhaogang Sun, Dapeng Bai, Yuhui Xu, Zhiling Li, Hairong Huang, Chuanyou Li, Shaofa Xu, and Li Li Copyright © 2015 Zaoxian Mei et al. All rights reserved. Parathyroidectomy Is Associated with Reduced Mortality in Hemodialysis Patients with Secondary Hyperparathyroidism Sun, 03 May 2015 12:07:43 +0000 Secondary hyperparathyroidism increases morbidity and mortality in hemodialysis patients. The Kidney Disease Outcomes Quality Initiative Guidelines recommend parathyroidectomy for patients with chronic kidney disease and parathyroid hormone concentrations exceeding 800 pg/mL; however, this concentration represents an arbitrary cut-off value. The present study was conducted to identify factors influencing mortality in hemodialysis patients with parathyroid hormone concentrations exceeding 800 pg/mL and to evaluate the effects of parathyroidectomy on outcome for these patients. Two hundred twenty-one hemodialysis patients with parathyroid hormone concentrations > 800 pg/mL from July 2004 to June 2010 were identified. 21.1% of patients (n = 60) received parathyroidectomy and 14.9% of patients (n = 33) died during a mean follow-up of 36 months. Patients with parathyroidectomy were found to have lower all-cause mortality (adjusted hazard ratio [aHR]: 0.34). Other independent predictors included age ≥ 65 years (aHR: 2.11) and diabetes mellitus (aHR: 3.80). For cardiovascular mortality, parathyroidectomy was associated with lower mortality (HR = 0.31) but with a marginal statistical significance (p = 0.061). In multivariate analysis, diabetes was the only significant predictor (aHR: 3.14). It is concluded that, for hemodialysis patients with parathyroid hormone concentrations greater than 800 pg/mL, parathyroidectomy is associated with reduced all-cause mortality. Tsung-Liang Ma, Peir-Haur Hung, Ing-Ching Jong, Chih-Yen Hiao, Yueh-Han Hsu, Pei-Chun Chiang, How-Ran Guo, and Kuan-Yu Hung Copyright © 2015 Tsung-Liang Ma et al. All rights reserved. Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression Sun, 03 May 2015 11:54:10 +0000 Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Several in vitro and in vivo studies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performed in vitro studies on ER-negative human breast carcinoma cells, MDA.MB231 and in vivo studies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphine in vitro enhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells. In vivo studies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression. Sabrina Bimonte, Antonio Barbieri, Domenica Rea, Giuseppe Palma, Antonio Luciano, Arturo Cuomo, Claudio Arra, and Francesco Izzo Copyright © 2015 Sabrina Bimonte et al. All rights reserved. Prediction of Metabolic Gene Biomarkers for Neurodegenerative Disease by an Integrated Network-Based Approach Sun, 03 May 2015 11:35:44 +0000 Neurodegenerative diseases (NDs), such as Parkinson’s disease (PD) and Huntington’s disease (HD), have become more and more common among aged people worldwide. One hallmark of NDs is the presence of intracellular accumulation of specific pathogenic proteins that may result from abnormal function of metabolic processes. Previously, we have developed a computational method named Met-express that predicted key enzyme-coding genes in cancer development by integrating cancer gene coexpression network with the metabolic network. Here, we applied Met-express to predict key enzyme-coding genes in both PD and HD. Functional enrichment analysis and literature review of predicted genes suggested that there might be some common pathogenic metabolic pathways for PD and HD. We further found that the predicted genes had significant functional association with known disease genes, with some of them already documented as biomarkers or therapeutic targets for NDs. As such, the predicted metabolic genes may be of use as novel biomarkers not only for ND diagnosis but also for potential therapeutic treatments. Qi Ni, Xianming Su, Jingqi Chen, and Weidong Tian Copyright © 2015 Qi Ni et al. All rights reserved. miR-155 and miR-484 Are Associated with Time to Progression in Metastatic Renal Cell Carcinoma Treated with Sunitinib Sun, 03 May 2015 11:28:13 +0000 Background. Sunitinib is a tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma. The main difficulty related to the treatment is the development of drug resistance followed by rapid progression of the disease. We analyzed tumor tissue of sunitinib treated patients in order to find miRNAs associated with therapeutic response. Methods. A total of 79 patients with metastatic renal cell carcinoma were included in our study. miRNA profiling in tumor tissue samples was performed by TaqMan Low Density Arrays and a group of selected miRNAs (miR-155, miR-374-5p, miR-324-3p, miR-484, miR-302c, and miR-888) was further validated by qRT-PCR. Normalized data were subjected to ROC and Kaplan-Meier analysis. Results. We reported decreased tissue levels of miR-155 and miR-484 as significantly associated with increased time to progression (miR-155: median TTP 5.8 versus 12.8 months, miR-484: median TTP 5.8 versus 8.9 months). Conclusion. miR-155 and miR-484 are potentially connected with sunitinib resistance and failure of the therapy. miR-155 is a known oncogene with direct influence on neovascularization. Biological role of miR-484 has to be clarified. Stratification of patients based on miRNA analysis would allow more personalized approach in therapy of metastatic renal cell carcinoma. Jana Merhautova, Renata Hezova, Alexandr Poprach, Alena Kovarikova, Lenka Radova, Marek Svoboda, Rostislav Vyzula, Regina Demlova, and Ondrej Slaby Copyright © 2015 Jana Merhautova et al. All rights reserved. Experimentally Induced Mammalian Models of Glaucoma Sun, 03 May 2015 11:16:10 +0000 A wide variety of animal models have been used to study glaucoma. Although these models provide valuable information about the disease, there is still no ideal model for studying glaucoma due to its complex pathogenesis. Animal models for glaucoma are pivotal for clarifying glaucoma etiology and for developing novel therapeutic strategies to halt disease progression. In this review paper, we summarize some of the major findings obtained in various glaucoma models and examine the strengths and limitations of these models. Makoto Ishikawa, Takeshi Yoshitomi, Charles F. Zorumski, and Yukitoshi Izumi Copyright © 2015 Makoto Ishikawa et al. All rights reserved.