BioMed Research International The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Wheeled Mobility Wed, 01 Apr 2015 14:09:24 +0000 Alicia M. Koontz, Dan Ding, Yih-Kuen Jan, Sonja de Groot, and Andrew Hansen Copyright © 2015 Alicia M. Koontz et al. All rights reserved. Kinematics of Rotation in Joints of the Lower Limbs and Pelvis during Gait: Early Results—SB ACLR Approach versus DB ACLR Approach Wed, 01 Apr 2015 09:46:04 +0000 It is difficult to find publications comparing rotation kinematics in large joints of the lower limbs and pelvis during gait in patients after single-bundle (SB) reconstruction of the anterior cruciate ligament (ACLR) with double-bundle (DB) ACLR of the knee. The aim of this study was to compare rotation kinematics in ankle, knee, and hip joints and the pelvis during gait in the 14th week after SB and DB ACLR. The subjects were males after SB () and DB () ACLR and a control group (). The values of kinematic parameters were recorded during internal (IR) and external (ER) rotation in the joints during gait using the BTS SMART. The SB ACLR group obtained significantly higher values of ER in the involved knee comparing to DB ACLR and controls and excessive IR in the hip comparing to controls. In the DB ACLR group, excessive ER was noted in the involved leg's foot. Comparing with the DB ACLR and control groups, SB ACLR subjects had more substantial disorders of rotation kinematics in the lower limb joints. However, in both ACLR groups, 14 weeks of postoperative physiotherapy were not enough to fully restore rotation kinematics in joints of the lower limbs during gait. Andrzej Czamara, Iga Markowska, Aleksandra Królikowska, Andrzej Szopa, and Małgorzata Domagalska Szopa Copyright © 2015 Andrzej Czamara et al. All rights reserved. Antiresistin RNA Oligonucleotide Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Attenuating Proinflammatory Cytokines Wed, 01 Apr 2015 08:10:59 +0000 The aim of this study was to determine whether inhibition of resistin by a synthetic antiresistin RNA (oligonucleotide) oligo ameliorates metabolic and histological abnormalities in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) in mice. The antiresistin RNA oligo and a scrambled control oligo (25 mg/kg of body weight) were i.p. injected to HFD mice. Serum metabolic parameters and hepatic enzymes were measured after 4-week treatment. The treatment significantly reduced epididymal fat and attenuated the elevated serum resistin, cholesterol, triglycerides, glucose, and insulin with an improved glucose tolerance test. Antiresistin RNA oligo also normalized serum AST and ALT levels with improved pathohistology of NAFLD. Immunoblotting and qRT-PCR revealed that decreased protein and mRNA expression of resistin in fat and liver tissues of the treated mice were associated with reduction of adipose TNF-α and IL-6 expression and secretion into circulation. mRNA and protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and sterol regulatory element-binding protein-1c (SREBP-1c) were also significantly decreased in the treated mice. Our results suggest that resistin may exacerbate NAFLD in metabolic syndrome through upregulating inflammatory cytokines and hepatic PEPCK and SREBP-1c. Antiresistin RNA oligo ameliorated metabolic abnormalities and histopathology of NAFLD through attenuating proinflammatory cytokines. Yi Tan, Xing Liang Jin, Weiguo Lao, Jane Kim, Linda Xiao, and Xianqin Qu Copyright © 2015 Yi Tan et al. All rights reserved. Radial Quantitative Ultrasound and Dual Energy X-Ray Absorptiometry: Intermethod Agreement for Bone Status Assessment in Children Wed, 01 Apr 2015 07:30:00 +0000 Aim. To validate a radial quantitative ultrasound (QUS) system with dual energy X-ray absorptiometry (DXA), a criterion technique in bone status assessment among children. Methods. Bone health was evaluated using a radial QUS system (Sunlight Omnisense 8000P) to measure the speed of sound (SOS) at one-third distal radius of the nondominant hand and DXA (Hologic QDR) was used to assess whole body bone mineral density (BMD). Results. Some 29.9% of the children were grossly misclassified according to quartiles of BMD and radial SOS. Poor agreement was observed between Z-scores of radial SOS and whole-body BMD (mean difference = 0.6 ± 0.9; 95% limits of agreement = −1.4 to 2.6). With a cut-off value of −1.0, radial SOS yielded satisfactory sensitivity (80%) and specificity (93%) for the detection of children with low BMD. Conclusion. The observed poor agreement in the present study suggests that radial QUS and DXA are not comparable and hence are not interchangeable in evaluating bone status of the children. Kar Hau Chong, Bee Koon Poh, Nor Aini Jamil, Nor Azmi Kamaruddin, and Paul Deurenberg Copyright © 2015 Kar Hau Chong et al. All rights reserved. Multiple Sclerosis in Older Adults: The Clinical Profile and Impact of Interferon Beta Treatment Wed, 01 Apr 2015 06:45:56 +0000 Background. We examined (1) patient characteristics and disease-modifying drug (DMD) exposure in late-onset (LOMS, ≥50 years at symptom onset) versus adult-onset (AOMS, 18–<50 years) MS and (2) the association between interferon-beta (IFNβ) and disability progression in older relapsing-onset MS adults (≥50 years). Methods. This retrospective study (1980–2004, British Columbia, Canada) included 358 LOMS and 5627 AOMS patients. IFNβ-treated relapsing-onset MS patients aged ≥50 (regardless of onset age, 90) were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFNβ eligibility were examined using survival analyses. Results. LOMS patients (6%) were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFNβ. Among older relapsing-onset MS adults, no significant association between IFNβ exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18–1.22) or historical controls (HR: 0.54; 95% CI: 0.20–1.42) were considered. Conclusion. LOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFNβ exposure was not significantly associated with reduced disability in older MS patients. Afsaneh Shirani, Yinshan Zhao, John Petkau, Paul Gustafson, Mohammad Ehsanul Karim, Charity Evans, Elaine Kingwell, Mia L. van der Kop, Joel Oger, and Helen Tremlett Copyright © 2015 Afsaneh Shirani et al. All rights reserved. Hippocampal-Prefrontal Circuit and Disrupted Functional Connectivity in Psychiatric and Neurodegenerative Disorders Tue, 31 Mar 2015 13:42:49 +0000 In rodents, the hippocampus has been studied extensively as part of a brain system responsible for learning and memory, and the prefrontal cortex (PFC) participates in numerous cognitive functions including working memory, flexibility, decision making, and rewarding learning. The neuronal projections from the hippocampus, either directly or indirectly, to the PFC, referred to as the hippocampal-prefrontal cortex (Hip-PFC) circuit, play a critical role in cognitive and emotional regulation and memory consolidation. Although in certain psychiatric and neurodegenerative diseases, structural connectivity viewed by imaging techniques has been consistently found to be associated with clinical phenotype and disease severity, the focus has moved towards the investigation of connectivity correlates of molecular pathology and coupling of oscillation. Moreover, functional and structural connectivity measures have been emerging as potential intermediate biomarkers for neuronal disorders. In this review, we summarize progress on the anatomic, molecular, and electrophysiological characters of the Hip-PFC circuit in cognition and emotion processes with an emphasis on oscillation and functional connectivity, revealing a disrupted Hip-PFC connectivity and electrical activity in psychiatric and neurodegenerative disorders as a promising candidate of neural marker for neuronal disorders. Ming Li, Cheng Long, and Li Yang Copyright © 2015 Ming Li et al. All rights reserved. Performance of Three Multipurpose Disinfecting Solutions with a Silicone Hydrogel Contact Lens Tue, 31 Mar 2015 13:41:16 +0000 Purpose. To evaluate the clinical performance of a silicone hydrogel (Si-Hy) soft contact lens (CL) in combination with three different multipurpose disinfecting solutions (MPDSs). Methods. This was a prospective, randomized, single-masked, crossover, and comparative study in which 31 habitual soft CL wearers were randomly assigned to one of the three MPDSs (Synergi, COMPLETE RevitaLens, and OPTI-FREE PureMoist) for 1 month with a 1-week wash-out period between each exposure. All subjects were successfully refitted with a Si-Hy CL (Biofinity). Subjects were then scheduled for follow-up visits after 1 month of lens wear, being evaluated at 2 and 8 hours after lens insertion. Visual Analogue Scales (VAS) were used to gauge comfort rating. Results. The tarsal conjunctiva showed a significantly different degree of lid redness between the MPDSs at the 2-hour visit (, Kruskal-Wallis test), being lower for COMPLETE RevitaLens compared to the other two MPDSs (Mann-Whitney test). Furthermore, a significantly different degree of lid roughness at the 8-hour visit was seen (, Kruskal-Wallis test), being higher for Synergi (Mann-Whitney test). The subjective comfort was similar with the three MPDSs. Conclusion. Tarsal conjunctival response should be also considered in the context of the clinical performance of MPDs at the ocular surface. Nery García-Porta, Laura Rico-del-Viejo, Helena Ferreira-Neves, Sofia C. Peixoto-de-Matos, Antonio Queirós, and José M. González-Méijome Copyright © 2015 Nery García-Porta et al. All rights reserved. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro Tue, 31 Mar 2015 13:24:36 +0000 Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation. Katharina Leitmeyer, Andrea Glutz, Vesna Radojevic, Cristian Setz, Nathan Huerzeler, Helen Bumann, Daniel Bodmer, and Yves Brand Copyright © 2015 Katharina Leitmeyer et al. All rights reserved. Oral Tori in Chronic Hemodialysis Patients Tue, 31 Mar 2015 13:15:12 +0000 Background. This study investigated the epidemiology of torus palatinus (TP) and torus mandibularis (TM) in hemodialysis patients and analyzed the influences of hyperparathyroidism on the formation of oral tori. Method. During 2013, 119 hemodialysis patients were recruited for dental examinations for this study. Results. The prevalence of oral tori in our sample group was high at 33.6% (40 of 119). The most common location of tori was TP (70.0%), followed by TM (20.0%), and then both TP and TM (10.0%). Of the 40 tori cases, most (67.5%) were <2 cm in size; moreover, the majority (52.5%) were flat in shape. In symmetry, most (70.0%) occurred in the midline, followed by bilateral sides (20.0%). Notably, the levels of intact parathyroid hormone did not differ in patients with or without tori (). Furthermore, patients with tori did not differ from patients without tori in inflammatory variables such as log high-sensitivity C-reactive protein () or nutritional variables such as albumin (). Finally, there were no differences between patients with and without tori in adequacy of dialysis (). Conclusions. Neither hyperparathyroidism nor inflammation malnutrition syndrome was found to contribute to the formation of oral tori in chronic hemodialysis patients. Further studies are warranted. Pei-Jung Chao, Huang-Yu Yang, Wen-Hung Huang, Cheng-Hao Weng, I-Kuan Wang, Aileen I. Tsai, and Tzung-Hai Yen Copyright © 2015 Pei-Jung Chao et al. All rights reserved. Emerging Roles of Focal Adhesion Kinase in Cancer Tue, 31 Mar 2015 12:19:30 +0000 Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor tyrosine kinase that enables activation by growth factor receptors or integrins in various types of human cancers. The kinase-dependent and kinase-independent scaffolding functions of FAK modulate the authentic signaling and fundamental functions not only in cancer cells but also in tumor microenvironment to facilitate cancer progression and metastasis. The overexpression and activation of FAK are usually investigated in primary or metastatic cancers and correlated with the poor clinical outcome, highlighting FAK as a potential prognostic marker and anticancer target. Small molecule inhibitors targeting FAK kinase activity or FAK-scaffolding functions impair cancer development in preclinical or clinical trials. In this review, we give an overview for FAK signaling in cancer cells as well as tumor microenvironment that provides new strategies for the invention of cancer development and malignancy. Yu-Ling Tai, Lih-Chyang Chen, and Tang-Long Shen Copyright © 2015 Yu-Ling Tai et al. All rights reserved. Relationship between Cognitive Performance and Motor Dysfunction in Patients with Parkinson’s Disease: A Pilot Cross-Sectional Study Tue, 31 Mar 2015 12:01:16 +0000 The aim of this pilot cross-sectional study was to extensively investigate the relationships between cognitive performance and motor dysfunction involving balance and gait ability in patients with Parkinson’s disease. Twenty subjects with Parkinson’s disease underwent a cognitive (outcomes: Frontal Assessment Battery-Italian version, Montreal overall Cognitive Assessment, Trail Making Test, Semantic Verbal Fluency Test, and Memory with Interference Test) and motor (outcomes: Berg Balance Scale, 10-Meter Walking Test, 6-Minute Walking Test, Timed Up and Go Test performed also under dual task condition, and Unified Parkinson’s Disease Rating Scale) assessment. Our correlation analyses showed that balance skills are significantly correlated with executive functions, cognitive impairment, and ability to switch attention between two tasks. Furthermore, functional mobility showed a significant correlation with cognitive impairment, verbal fluency, and ability to switch attention between two tasks. In addition, the functional mobility evaluated under the dual task condition showed a significant correlation with cognitive impairment and ability to switch attention between two tasks. These findings might help early identification of cognitive deficits or motor dysfunctions in patients with Parkinson’s disease who may benefit from rehabilitative strategies. Future prospective larger-scale studies are needed to strengthen our results. Valentina Varalta, Alessandro Picelli, Cristina Fonte, Stefania Amato, Camilla Melotti, Vanja Zatezalo, Leopold Saltuari, and Nicola Smania Copyright © 2015 Valentina Varalta et al. All rights reserved. Temporal Changes of Microarchitectural and Mechanical Parameters of Cancellous Bone in the Osteoporotic Rabbit Tue, 31 Mar 2015 11:57:44 +0000 This study was aimed at elucidating the temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit model induced by ovariectomy (OVX) combined with glucocorticoid (GC) administration. Osteoporotic (OP) group received bilateral OVX combined with injections of GC, while sham group only received sham operation. Cancellous bone quality in vertebrae and femoral condyles in each group was assessed by DXA, μCT, nanoindentation, and biomechanical tests at pre-OVX and 4, 6, and 8 weeks after injection. With regard to femoral condyles, nanoindentation test could detect significant decline in tissue modulus and hardness at 4 weeks. However, BMD and microarchitecture of femoral condylar cancellous bone changed significantly at 6 weeks. In vertebrae, BMD, microarchitecture, nanoindentation, and biomechanical tests changed significantly at 4 weeks. Our data demonstrated that temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit were significant. The temporal changes of cancellous bone in different anatomical sites might be different. The nanoindentation method could detect the changes of bone quality at an earlier stage at both femoral condyle and vertebra in the osteoporotic rabbit model than other methods (μCT, BMD). Xin-Xin Wen, Chao Xu, Fa-Qi Wang, Ya-Fei Feng, Xiong Zhao, Ya-Bo Yan, and Wei Lei Copyright © 2015 Xin-Xin Wen et al. All rights reserved. Functional Roles of Calreticulin in Cancer Biology Tue, 31 Mar 2015 11:36:28 +0000 Calreticulin is a highly conserved endoplasmic reticulum chaperone protein which participates in various cellular processes. It was first identified as a Ca2+-binding protein in 1974. Accumulated evidences indicate that calreticulin has great impacts for the development of different cancers and the effect of calreticulin on tumor formation and progression may depend on cell types and clinical stages. Cell surface calreticulin is considered as an “eat-me” signal and promotes phagocytic uptake of cancer cells by immune system. Moreover, several reports reveal that manipulation of calreticulin levels profoundly affects cancer cell proliferation and angiogenesis as well as differentiation. In addition to immunogenicity and tumorigenesis, interactions between calreticulin and integrins have been described during cell adhesion, which is an essential process for cancer metastasis. Integrins are heterodimeric transmembrane receptors which connect extracellular matrix and intracellular cytoskeleton and trigger inside-out or outside-in signaling transduction. More and more evidences reveal that proteins binding to integrins might affect integrin-cytoskeleton interaction and therefore influence ability of cell adhesion. Here, we reviewed the biological roles of calreticulin and summarized the potential mechanisms of calreticulin in regulating mRNA stability and therefore contributed to cancer metastasis. Yi-Chien Lu, Wen-Chin Weng, and Hsinyu Lee Copyright © 2015 Yi-Chien Lu et al. All rights reserved. Integrative Analysis of CRISPR/Cas9 Target Sites in the Human HBB Gene Tue, 31 Mar 2015 09:39:46 +0000 Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the human β-globin gene (HBB) and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction. Yumei Luo, Detu Zhu, Zhizhuo Zhang, Yaoyong Chen, and Xiaofang Sun Copyright © 2015 Yumei Luo et al. All rights reserved. Oxidative/Antioxidative Status in Obese and Sport Trained Children: A Comparative Study Tue, 31 Mar 2015 08:16:45 +0000 The aim of the study was to compare oxidative/antioxidative status in obese and sport trained children and to correlate obtained redox markers with anthropometrical measurements, body composition parameters, and adipokines levels. 78 (44 males) obese (SG) and 80 (40 males) normal weight sport trained (CG) children matched for age and Tanner stage were recruited for the study. Body composition parameters and basal metabolic rate (BMR) were assessed by bioelectrical impedance analysis (BIA). Oxidative/antioxidative status was evaluated in plasma by total oxidative status (PerOX), oxidized-LDL cholesterol (oxLDL), total antioxidative capacity (ImAnOx), and glutathione peroxidase activity (GPx). Leptin and adiponectin levels and adiponectin/leptin ratio (A/L) were also investigated. OxLDL was higher in SG versus CG (P < 0.05), but ImAnOx and GPx were reduced in SG versus CG (P < 0.01). Redox markers correlated significantly with BMI Z-score, WHR, WHtR, body composition parameters, leptin (in boys only), and A/L ratio (in boys only) in SG and in a whole studied population. PerOX significantly correlated with BMR in the CG. Antioxidative/oxidative status in obese children is significantly impaired and related adipose tissue excess and its hormonal activity. Oxidative status assessed by PerOx is also high in sport trained children but antioxidative defense is significantly more efficient with no overproduction of oxidized LDL. Pawel Matusik, Zofia Prokopowicz, Berenika Norek, Magdalena Olszanecka-Glinianowicz, Jerzy Chudek, and Ewa Malecka-Tendera Copyright © 2015 Pawel Matusik et al. All rights reserved. Radiation Oncology and Medical Physics Tue, 31 Mar 2015 07:21:05 +0000 Tsair-Fwu Lee, Jack Yang, Cheng-Shie Wuu, An Liu, Fu-Min Fang, and Shyh-An Yeh Copyright © 2015 Tsair-Fwu Lee et al. All rights reserved. Optimizing Perfusion-Decellularization Methods of Porcine Livers for Clinical-Scale Whole-Organ Bioengineering Tue, 31 Mar 2015 06:37:14 +0000 Aim. To refine the decellularization protocol of whole porcine liver, which holds great promise for liver tissue engineering. Methods. Three decellularization methods for porcine livers (1% sodium dodecyl sulfate (SDS), 1% Triton X-100 + 1% sodium dodecyl sulfate, and 1% sodium deoxycholate + 1% sodium dodecyl sulfate) were studied. The obtained liver scaffolds were processed for histology, residual cellular content analysis, and extracellular matrix (ECM) components evaluation to investigate decellularization efficiency and ECM preservation. Rat primary hepatocytes were seeded into three kinds of scaffold to detect the biocompatibility. Results. The whole liver decellularization was successfully achieved following all three kinds of treatment. SDS combined with Triton had a high efficacy of cellular removal and caused minimal disruption of essential ECM components; it was also the most biocompatible procedure for primary hepatocytes. Conclusion. We have refined a novel, standardized, time-efficient, and reproducible protocol for the decellularization of whole liver which can be further adapted to liver tissue engineering. Qiong Wu, Ji Bao, Yong-jie Zhou, Yu-jia Wang, Zheng-gui Du, Yu-jun Shi, Li Li, and Hong Bu Copyright © 2015 Qiong Wu et al. All rights reserved. Does High Thoracic Epidural Analgesia with Levobupivacaine Preserve Myocardium? A Prospective Randomized Study Tue, 31 Mar 2015 06:17:10 +0000 Background. Our study aimed to compare HTEA and intravenous patient-controlled analgesia (PCA) in patients undergoing coronary bypass graft surgery (CABG), based on haemodynamic parameters and myocardial functions. Materials and Methods. The study included 34 patients that were scheduled for elective CABG, who were randomly divided into 2 groups. Anesthesia was induced and maintained with total intravenous anesthesia in both groups while intravenous PCA with morphine was administered in Group 1 and infusion of levobupivacaine was administered from the beginning of the anesthesia in Group 2 by thoracic epidural catheter. Blood samples were obtained presurgically, at 6 and 24 hours after surgery for troponin I, creatinine kinase-MB (CK-MB), total antioxidant capacity, and malondialdehyde. Postoperative pain was evaluated every 4 hours until 24 hours via VAS. Results. There were significant differences in troponin I or CK-MB values between the groups at postsurgery 6 h and 24 h. Heart rate and mean arterial pressure in Group 1 were significantly higher than in Group 2 at all measurements. Cardiac index in Group 2 was significantly higher than in Group 1 at all measurements. Conclusion. Patients that underwent CABG and received HTEA had better myocardial function and perioperative haemodynamic parameters than those who did not receive HTEA. Serife Gokbulut Bektas, Sema Turan, Umit Karadeniz, Burcin Ozturk, Soner Yavas, Dilan Biricik, Gul Sevim Saydam, and Ozcan Erdemli Copyright © 2015 Serife Gokbulut Bektas et al. All rights reserved. In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments Mon, 30 Mar 2015 13:56:04 +0000 Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genus Leishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways of Leishmania include several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes in Leishmania could be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93 Leishmania energy metabolism targets. Using each gene’s designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis. Lourival A. Silva, Marina C. Vinaud, Ana Maria Castro, Pedro Vítor L. Cravo, and José Clecildo B. Bezerra Copyright © 2015 Lourival A. Silva et al. All rights reserved. A New Double Stranded RNA Suppresses Bladder Cancer Development by Upregulating p21Waf1/CIP1 Expression Mon, 30 Mar 2015 12:59:07 +0000 We have previously demonstrated that miR-1180-5p has potent ability to upregulate p21 expression by targeting promoter and inhibit bladder cancer. This prompted us to conjecture that a candidate dsRNA (dsP21-397) with perfect complementarity to the miR-1180-5p target site of p21 promoter may also trigger p21 expression. Transfection of dsP21-397 into T24 and EJ cells significantly activated p21 expression at 72 h and the activation presented in a time-course and dose-dependent manner. Moreover, the p21-activated activities of dsP21-397 and miR-1180-5p are not significantly different. Overexpression of p21 downregulated Cyclin D1, CDK4/6, and Cyclin A2 expression, and thereby induced cell cycle arrest and inhibited proliferation. Moreover, dsP21-397 suppressed bladder cancer largely depended on manipulating p21. In conclusion, our study identifies a pair of miRNA-dsRNA mediating endogenous p21 overexpression. Chenghe Wang, Qiangqiang Ge, Zhong Chen, Jia Hu, Fan Li, Xiaodong Song, Hua Xu, and Zhangqun Ye Copyright © 2015 Chenghe Wang et al. All rights reserved. Microbiological Quality of Ready-to-Eat Vegetables Collected in Mexico City: Occurrence of Aerobic-Mesophilic Bacteria, Fecal Coliforms, and Potentially Pathogenic Nontuberculous Mycobacteria Mon, 30 Mar 2015 12:44:05 +0000 The aims of this study were to evaluate the microbiological quality and the occurrence of nontuberculous mycobacteria (NTM) in a variety of salads and sprouts from supermarkets and street vendors in Mexico City. Aerobic-mesophilic bacteria (AMB) were present in 100% of RTE-salads samples; 59% of samples were outside guidelines range (>5.17 log10 CFU per g). Although fecal coliforms (FC) were present in 32% of samples, only 8% of them exceeded the permissible limit (100 MPN/g). Regarding the 100 RTE-sprouts, all samples were also positive for AMB and total coliforms (TC) and 69% for FC. Seven NTM species were recovered from 7 salad samples; they included three M. fortuitum, two M. chelonae, one M. mucogenicum, and one M. sp. Twelve RTE-sprouts samples harbored NTM, which were identified as M. porcinum (five), M. abscessus (two), M. gordonae (two), M. mucogenicum (two), and M. avium complex (one). Most RTE-salads and RTE-sprouts had unsatisfactory microbiological quality and some harbored NTM associated with illness. No correlation between the presence of coliforms and NTM was found. Overall, these results suggest that RTE-salads and RTE-sprouts might function as vehicles for NTM transmission in humans; hence, proper handling and treatment before consumption of such products might be recommendable. Jorge Francisco Cerna-Cortes, Nancy Leon-Montes, Ana Laura Cortes-Cueto, Laura P. Salas-Rangel, Addy Cecilia Helguera-Repetto, Daniel Lopez-Hernandez, Sandra Rivera-Gutierrez, Elizabeth Fernandez-Rendon, and Jorge Alberto Gonzalez-y-Merchand Copyright © 2015 Jorge Francisco Cerna-Cortes et al. All rights reserved. Antibiotic-Resistant Vibrios in Farmed Shrimp Mon, 30 Mar 2015 11:22:44 +0000 Antimicrobial susceptibility pattern was determined in 100 strains of Vibrio isolated from the Litopenaeus vannamei shrimp and identified phenotypically. A high antibiotic-resistance index (75%) was observed, with the following phenotypic profiles: monoresistance (), cross-resistance to β-lactams () and multiple resistance (). Plasmid resistance was characterized for penicillin (), penicillin + ampicillin (), penicillin + aztreonam (), and ampicillin (). Resistance to antimicrobial drugs by the other strains () was possibly mediated by chromosomal genes. The findings of this study support the conclusion that the cultured shrimps can be vehicles of vibrios resistant to β-lactam and tetracycline. Renata Albuquerque Costa, Rayza Lima Araújo, Oscarina Viana Souza, and Regine Helena Silva dos Fernandes Vieira Copyright © 2015 Renata Albuquerque Costa et al. All rights reserved. Induced Second Trimester Abortion and Associated Factors in Amhara Region Referral Hospitals Mon, 30 Mar 2015 10:18:51 +0000 Background. Although the vast majority of abortions are performed in the first trimester, still 10–15% of terminations of pregnancies have taken place in the second trimester period globally. As compared to first trimester, second trimester abortions are disproportionately contribute for maternal morbidity and mortality especially in low-resource countries where access to safe second trimester abortion is limited. The main aim of this study was to assess the prevalence and associated factors of induced second trimester abortion in Amhara region referral hospitals, northwest Ethiopia. Methods. Institution based cross-sectional study was conducted in Amhara region referral hospitals among 416 women who sought abortion services. Participants were selected using systematic sampling technique. Data were collected using pretested structured questionnaire through interviewing. After the data were entered and analyzed; variables which have value < 0.2 in bivariate analysis, not colinear, were entered into multiple logistic regressions to see the net effect with 95% CI and value < 0.05. Results. The prevalence of induced second trimester abortion was 19.2%. Being rural (AOR = 1.86 [95% CI = 1.11–3.14]), having irregular menstrual cycle (AOR = 1.76 [95% CI = 1.03–2.98]), not recognizing their pregnancy at early time (AOR = 2.05 [95% CI = 1.21–3.48]), and having logistics related problems (AOR = 2.37 [95% CI = 1.02–5.53]) were found to have statistically significant association with induced second trimester abortion. Conclusion. Induced second trimester abortion is high despite the availability of first trimester abortion services. Therefore, increase accessibility and availability of safe second trimester abortion services below referral level, counseling and logistical support are helpful to minimize late abortions. Amlaku Mulat, Hinsermu Bayu, Habtamu Mellie, and Amare Alemu Copyright © 2015 Amlaku Mulat et al. All rights reserved. Duck RIG-I CARD Domain Induces the Chicken IFN-β by Activating NF-κB Mon, 30 Mar 2015 10:08:34 +0000 Retinoic acid-inducible gene I- (RIG-I-) like receptors (RLRs) have recently been identified as cytoplasmic sensors for viral RNA. RIG-I, a member of RLRs family, plays an important role in innate immunity. Although previous investigations have proved that RIG-I is absent in chickens, it remains largely unknown whether the chicken can respond to RIG-I ligand. In this study, the eukaryotic expression vectors encoding duRIG-I full length (duck RIG-I, containing all domains), duRIG-I N-terminal (containing the two caspase activation and recruitment domain, CARDs), and duRIG-I C-terminal (containing helicase and regulatory domains) labeled with 6*His tags were constructed successfully and detected by western blotting. Luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA) detected the duRIG-I significantly activated NF-κB and induced the expression of IFN-β when polyinosinic-polycytidylic acid (poly[I:C], synthetic double-stranded RNA) challenges chicken embryonic fibroblasts cells (DF1 cells), while the duRIG-I was inactive in the absence of poly[I:C]. Further analysis revealed that the CARDs (duRIG-I-N) induced IFN-β production regardless of the presence of poly[I:C], while the CARD-lacking duRIG-I (duRIG-I-C) was not capable of activating downstream signals. These results indicate that duRIG-I CARD domain plays an important role in the induction of IFN-β and provide a basis for further studying the function of RIG-I in avian innate immunity. Yang Chen, Zhengyang Huang, Bin Wang, Qinming Yu, Ran Liu, Qi Xu, Guobin Chang, Jiatong Ding, and Guohong Chen Copyright © 2015 Yang Chen et al. All rights reserved. The Water Cycle, a Potential Source of the Bacterial Pathogen Bacillus cereus Mon, 30 Mar 2015 09:19:27 +0000 The behaviour of the sporulating soil-dwelling Bacillus cereus sensu lato (B. cereus sl) which includes foodborne pathogenic strains has been extensively studied in relation to its various animal hosts. The aim of this environmental study was to investigate the water compartments (rain and soil water, as well as groundwater) closely linked to the primary B. cereus sl reservoir, for which available data are limited. B. cereus sl was present, primarily as spores, in all of the tested compartments of an agricultural site, including water from rain to groundwater through soil. During rain events, leachates collected after transfer through the soil eventually reached the groundwater and were loaded with B. cereus sl. In groundwater samples, newly introduced spores of a B. cereus model strain were able to germinate, and vegetative cells arising from this event were detected for up to 50 days. This first B. cereus sl investigation in the various types of interrelated environments suggests that the consideration of the aquatic compartment linked to soil and to climatic events should provide a better understanding of B. cereus sl ecology and thus be relevant for a more accurate risk assessment of food poisoning caused by B. cereus sl pathogenic strains. Julien Brillard, Christian M. S. Dupont, Odile Berge, Claire Dargaignaratz, Stéphanie Oriol-Gagnier, Claude Doussan, Véronique Broussolle, Marina Gillon, Thierry Clavel, and Annette Bérard Copyright © 2015 Julien Brillard et al. All rights reserved. Listeriosis Outbreaks in British Columbia, Canada, Caused by Soft Ripened Cheese Contaminated from Environmental Sources Mon, 30 Mar 2015 09:17:07 +0000 Soft ripened cheese (SRC) caused over 130 foodborne illnesses in British Columbia (BC), Canada, during two separate listeriosis outbreaks. Multiple agencies investigated the events that lead to cheese contamination with Listeria monocytogenes (L.m.), an environmentally ubiquitous foodborne pathogen. In both outbreaks pasteurized milk and the pasteurization process were ruled out as sources of contamination. In outbreak A, environmental transmission of L.m. likely occurred from farm animals to personnel to culture solutions used during cheese production. In outbreak B, birds were identified as likely contaminating the dairy plant’s water supply and cheese during the curd-washing step. Issues noted during outbreak A included the risks of operating a dairy plant in a farm environment, potential for transfer of L.m. from the farm environment to the plant via shared toilet facilities, failure to clean and sanitize culture spray bottles, and cross-contamination during cheese aging. L.m. contamination in outbreak B was traced to wild swallows defecating in the plant’s open cistern water reservoir and a multibarrier failure in the water disinfection system. These outbreaks led to enhanced inspection and surveillance of cheese plants, test and release programs for all SRC manufactured in BC, improvements in plant design and prevention programs, and reduced listeriosis incidence. Lorraine McIntyre, Lynn Wilcott, and Monika Naus Copyright © 2015 Lorraine McIntyre et al. All rights reserved. Effects of PMA (PHORBOL-12-MYRISTATE-13-ACETATE) on the Developing Rodent Brain Mon, 30 Mar 2015 09:05:34 +0000 Perinatal infections have a negative impact on brain development. However, the underlying mechanisms leading to neurological impairment are not completely understood and reliable models of inflammation are urgently needed. Using phorbol-myristate-acetate as an activator of inflammation, we investigated the effect on the developing rodent brain. Neonatal rats and mice deficient in IL-18 or IRAK-4 were exposed to PMA. Brains were assessed for regulation of pro- and anti-inflammatory cytokines and cell death 24 hrs, 7 and 14 days after treatment. PMA induced an inflammatory response and caused widespread neurodegeneration in the brains of 3- and 7-day-old rats. In contrast, 14-day-old rats were resistant to the neurotoxic effect of PMA. Histological evaluation at the age of 14 and 21 days revealed a destruction of the cortical microstructure with decreased numerical density of neuronal cells. Mice deficient in IL-18 or IRAK-4 were protected against PMA induced brain injury. PMA treatment during a vulnerable period can alter brain development. IL-18 and IRAK-4 appear to be important for the development of PMA induced injury. Mark Dzietko, Maria Hahnemann, Oliver Polley, Marco Sifringer, Ursula Felderhoff-Mueser, and Christoph Bührer Copyright © 2015 Mark Dzietko et al. All rights reserved. Corrigendum to “Semiphysiological versus Empirical Modelling of the Population Pharmacokinetics of Free and Total Cefazolin during Pregnancy” Mon, 30 Mar 2015 08:49:38 +0000 J. G. Coen van Hasselt, Karel Allegaert, Kristel van Calsteren, Jos H. Beijnen, Jan H. M. Schellens, and Alwin D. R. Huitema Copyright © 2015 J. G. Coen van Hasselt et al. All rights reserved. Advances in Gene Delivery Systems Mon, 30 Mar 2015 06:49:34 +0000 Surendra Nimesh, Sabina Halappanavar, Nagendra K. Kaushik, and Pradeep Kumar Copyright © 2015 Surendra Nimesh et al. All rights reserved. Haematuria in Postrenal Transplant Patients Mon, 30 Mar 2015 06:22:46 +0000 Haematuria has a prevalence of 12% in the postrenal transplant patient population. It heralds potentially dangerous causes which could threaten graft loss. It is important to consider causes in light of the unique, urological, and immunological standpoints of these patients. We review the literature on common causes of haematuria in postrenal transplant patients and suggest the salient approach to the evaluation of this condition. A major cause of haematuria is urinary tract infections. There should be a higher index of suspicion for mycobacterial, fungal, and viral infection in this group of immunosuppressed patients. Measures recommended in the prevention of urinary tract infections include early removal of foreign bodies as well as prophylactic antibiotics during the early transplant phase. Another common cause of haematuria is that of malignancies, in particular, renal cell carcinomas. When surgically managing cancer in the setting of a renal transplant, one has to be mindful of the limited retropubic space and the need to protect the anastomoses. Other causes include graft rejections, recurrences of primary disease, and calculus formation. It is important to perform a comprehensive evaluation with the aid of an experienced multidisciplinary transplant team. Ziting Wang, Anantharaman Vathsala, and Ho Yee Tiong Copyright © 2015 Ziting Wang et al. All rights reserved.