BioMed Research International The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Advancements in RNASeqGUI towards a Reproducible Analysis of RNA-Seq Experiments Wed, 10 Feb 2016 13:50:15 +0000 We present the advancements and novelties recently introduced in RNASeqGUI, a graphical user interface that helps biologists to handle and analyse large data collected in RNA-Seq experiments. This work focuses on the concept of reproducible research and shows how it has been incorporated in RNASeqGUI to provide reproducible (computational) results. The novel version of RNASeqGUI combines graphical interfaces with tools for reproducible research, such as literate statistical programming, human readable report, parallel executions, caching, and interactive and web-explorable tables of results. These features allow the user to analyse big datasets in a fast, efficient, and reproducible way. Moreover, this paper represents a proof of concept, showing a simple way to develop computational tools for Life Science in the spirit of reproducible research. Francesco Russo, Dario Righelli, and Claudia Angelini Copyright © 2016 Francesco Russo et al. All rights reserved. Serum Sialic Acid Level Is Significantly Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Chinese Population: A Cross-Sectional Study Wed, 10 Feb 2016 12:28:35 +0000 Background/Aim. To investigate the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a nonobese Chinese population. Methods. A cross-sectional study was performed among the 5916 adults who took their annual health examinations at International Health Care Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from December 2013 to November 2014. Results. A total of 693 (11.71%) subjects fulfilled the diagnostic criteria of NAFLD, and NAFLD patients had significantly higher serum SA levels than controls (). The prevalence of NAFLD was positively associated with serum SA levels ( for trend <0.001). Serum sialic acid levels are significantly associated with features of metabolic syndrome (). Multivariate logistic regression analysis showed that serum SA level was significantly associated with risk for NAFLD (odds ratio: 1.018, 95%; confidence interval: 1.007–1.030; ). Conclusions. Our results suggest for the first time that NAFLD patients had higher serum SA level than controls, and increased serum SA level is significantly associated with risk for NAFLD in a large nonobese Chinese population. Zhenya Lu, Han Ma, Chengfu Xu, Zhou Shao, Chao Cen, and Youming Li Copyright © 2016 Zhenya Lu et al. All rights reserved. Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Hepatocytes In Vitro and In Vivo Wed, 10 Feb 2016 09:02:21 +0000 Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo. Gai Xue, Xiaolei Han, Xin Ma, Honghai Wu, Yabin Qin, Jianfang Liu, Yuqin Hu, Yang Hong, and Yanning Hou Copyright © 2016 Gai Xue et al. All rights reserved. Energy Modulated Photon Radiotherapy: A Monte Carlo Feasibility Study Tue, 09 Feb 2016 05:52:29 +0000 A novel treatment modality termed energy modulated photon radiotherapy (EMXRT) was investigated. The first step of EMXRT was to determine beam energy for each gantry angle/anatomy configuration from a pool of photon energy beams (2 to 10 MV) with a newly developed energy selector. An inverse planning system using gradient search algorithm was then employed to optimize photon beam intensity of various beam energies based on presimulated Monte Carlo pencil beam dose distributions in patient anatomy. Finally, 3D dose distributions in six patients of different tumor sites were simulated with Monte Carlo method and compared between EMXRT plans and clinical IMRT plans. Compared to current IMRT technique, the proposed EMXRT method could offer a better paradigm for the radiotherapy of lung cancers and pediatric brain tumors in terms of normal tissue sparing and integral dose. For prostate, head and neck, spine, and thyroid lesions, the EMXRT plans were generally comparable to the IMRT plans. Our feasibility study indicated that lower energy (<6 MV) photon beams could be considered in modern radiotherapy treatment planning to achieve a more personalized care for individual patient with dosimetric gains. Ying Zhang, Yuanming Feng, Xin Ming, and Jun Deng Copyright © 2016 Ying Zhang et al. All rights reserved. Penis Allotransplantation in Beagle Dog Mon, 08 Feb 2016 13:22:04 +0000 This is an original research of penis allotransplantation. The paper presents an experiment allogenic penis transplantation model in Beagles, with a focus on recovery of blood supply and changes in tissue architecture. Twenty adult Beagles were allocated to 10 pairs for penile transplantation. After operation, the skin and glans were observed. If adverse symptoms occurred, the transplanted penis was resected and pathologically examined. Frequency of urination, urinary stream, and patency level were recorded 7 days after transplantation. Cystourethrography was performed on Day 10. The transplanted penises were resected on Day 14 for pathological examination. The research showed that transplanted penises survived after allotransplantation, and the dogs regained urination ability. Penis autotransplantation in Beagles is feasible. This preliminary study shows a potential for application of this new procedure for penis transplantation in humans. Yongbin Zhao, Weilie Hu, Lichao Zhang, Fei Guo, Wei Wang, Bangqi Wang, and Changzheng Zhang Copyright © 2016 Yongbin Zhao et al. All rights reserved. The Alternative Faces of Macrophage Generate Osteoclasts Mon, 08 Feb 2016 11:35:51 +0000 The understanding of how osteoclasts are generated and whether they can be altered by inflammatory stimuli is a topic of particular interest for osteoclastogenesis. It is known that the monocyte/macrophage lineage gives rise to osteoclasts (OCs) by the action of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL), which induce cell differentiation through their receptors, c-fms and RANK, respectively. The multinucleated giant cells (MGCs) generated by the engagement of RANK/RANKL are typical OCs. Nevertheless, very few studies have addressed the question of which subset of macrophages generates OCs. Indeed, two main subsets of macrophages are postulated, the inflammatory or classically activated type (M1) and the anti-inflammatory or alternatively activated type (M2). It has been proposed that macrophages can be polarized in vitro towards a predominantly M1 or M2 phenotype with the addition of granulocyte macrophage- (GM-) CSF or M-CSF, respectively. Various inflammatory stimuli known to induce macrophage polarization, such as LPS or TNF-, can alter the type of MGC obtained from RANKL-induced differentiation. This review aims to highlight the role of immune-related stimuli and factors in inducing macrophages towards the osteoclastogenesis choice. N. Lampiasi, R. Russo, and F. Zito Copyright © 2016 N. Lampiasi et al. All rights reserved. A Prediction Model for Membrane Proteins Using Moments Based Features Sun, 07 Feb 2016 15:42:21 +0000 The most expedient unit of the human body is its cell. Encapsulated within the cell are many infinitesimal entities and molecules which are protected by a cell membrane. The proteins that are associated with this lipid based bilayer cell membrane are known as membrane proteins and are considered to play a significant role. These membrane proteins exhibit their effect in cellular activities inside and outside of the cell. According to the scientists in pharmaceutical organizations, these membrane proteins perform key task in drug interactions. In this study, a technique is presented that is based on various computationally intelligent methods used for the prediction of membrane protein without the experimental use of mass spectrometry. Statistical moments were used to extract features and furthermore a Multilayer Neural Network was trained using backpropagation for the prediction of membrane proteins. Results show that the proposed technique performs better than existing methodologies. Ahmad Hassan Butt, Sher Afzal Khan, Hamza Jamil, Nouman Rasool, and Yaser Daanial Khan Copyright © 2016 Ahmad Hassan Butt et al. All rights reserved. Development and Validation of a Questionnaire to Assess Multimorbidity in Primary Care: An Indian Experience Sun, 07 Feb 2016 14:19:14 +0000 Multimorbidity remains an underexplored domain in Indian primary care. We undertook a study to assess the prevalence, correlates, and outcomes of multimorbidity in primary care settings in India. This paper describes the process of development and validation of our data collection tool “Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC).” An iterative process comprising desk review, chart review, and expert consultations was undertaken to generate the questionnaire. The MAQ-PC contained items on chronic conditions, health care utilization, health related quality of life, disease severity, and sociodemographics. It was first tested with twelve adults for comprehensibility followed by test-retest reliability with 103 patients from four primary care practices. For interrater reliability, two interviewers separately administered the questionnaire to sixteen patients. MAQ-PC displayed strong internal consistency (Cronbach’s alpha: 0.69), interrater reliability (Cohen’s Kappa: 0.78–1), and test-retest reliability (ICC: 0.970–0.741). Substantial concordance between self-report and physician diagnosis (Scott Kappa: 0.59–1.0) was observed for listed chronic conditions indicating strong concurrent validity. Nearly 54% had one chronic condition and 23.3% had multimorbidity. Our findings demonstrate MAQ-PC to be a valid and reliable measure of multimorbidity in primary care practice and suggest its potential utility in multimorbidity research in India. Sanghamitra Pati, Mohammad Akhtar Hussain, Subhashisa Swain, Chris Salisbury, Job F. M. Metsemakers, J. André Knottnerus, and Marjan van den Akker Copyright © 2016 Sanghamitra Pati et al. All rights reserved. PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data Sun, 07 Feb 2016 14:17:44 +0000 The functionality of most proteins is regulated by protein-protein interactions. Hence, the comprehensive characterization of the interactome is the next milestone on the path to understand the biochemistry of the cell. A powerful method to detect protein-protein interactions is a combination of coimmunoprecipitation or affinity purification with quantitative mass spectrometry. Nevertheless, both methods tend to precipitate a high number of background proteins due to nonspecific interactions. To address this challenge the software Protein-Protein-Interaction-Optimizer (PIPINO) was developed to perform an automated data analysis, to facilitate the selection of bona fide binding partners, and to compare the dynamic of interaction networks. In this study we investigated the STAT1 interaction network and its activation dependent dynamics. Stable isotope labeling by amino acids in cell culture (SILAC) was applied to analyze the STAT1 interactome after streptavidin pull-down of biotagged STAT1 from human embryonic kidney 293T cells with and without activation. Starting from more than 2,000 captured proteins 30 potential STAT1 interaction partners were extracted. Interestingly, more than 50% of these were already reported or predicted to bind STAT1. Furthermore, 16 proteins were found to affect the binding behavior depending on STAT1 phosphorylation such as STAT3 or the importin subunits alpha 1 and alpha 6. Stefan Kalkhof, Stefan Schildbach, Conny Blumert, Friedemann Horn, Martin von Bergen, and Dirk Labudde Copyright © 2016 Stefan Kalkhof et al. All rights reserved. Coxiella burnetii Seroprevalence and Risk Factors in Cattle Farmers and Farm Residents in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China Thu, 04 Feb 2016 13:32:47 +0000 Little is known about Coxiella burnetii infection among cattle farmers and farm residents in China. Thus, the present study was conducted to detect the seroprevalence of C. burnetii infection and estimate associated risk factors among cattle farmers and farm residents in China. A cross-sectional study was designed, and sera of 362 people living or working on 106 cattle farms were tested for C. burnetii IgG and IgM antibodies by immunofluorescence assay. Overall C. burnetii seroprevalence was 35.6% (129/362, 95% CI: 30.70–40.57), and 112 participants had experienced a past infection and seventeen (4.7%) had experienced a relatively recent infection. In the final combined multilevel model, the following activities were significantly associated with presence of antibodies against C. burnetii: milking cattle, providing general healthcare to cattle, providing birth assistance, contact dead-born animals, urbanization, and presence of mice and/or rats in the stable. Moreover, presence of disinfection equipment was a significant protective factor. This is the first study addressing the seroprevalence and risk factors of C. burnetii infection in cattle farmers and farm residents in three northeastern provinces and Inner Mongolia Autonomous Region, China. Wu-Wen Sun, Wei Cong, Mao-Hui Li, Chun-Feng Wang, Xiao-Feng Shan, and Ai-Dong Qian Copyright © 2016 Wu-Wen Sun et al. All rights reserved. Optimizing Human Bile Preparation for Two-Dimensional Gel Electrophoresis Thu, 04 Feb 2016 08:48:31 +0000 Aims. Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established. Methods and Material. The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE) profiling quality, including number of protein spots and spot distribution. Results. The total protein of bile fluid in benign biliary disorders was 0.797 ± 0.465 μg/μL. The sample preparation method using acetone precipitation first followed by 2D Clean-Up kit protein extraction resulted in better quality of 2DE gel images in terms of resolution as compared with other sample preparation methods. Using this protocol, we obtained approximately 558 protein spots on the gel images and with better protein spots presentation of haptoglobin, serum albumin, serotransferrin, and transthyretin. Conclusions. Protein samples of bile prepared using acetone precipitation followed by 2D Clean-Up kit exhibited high protein resolution and significant protein profile. This optimized protein preparation protocol can effectively concentrate bile proteins, remove abundant proteins and debris, and yield clear presentation of nonabundant proteins and its isoforms on 2-dimensional electrophoresis gel images. Hao-Tsai Cheng, Sen-Yung Hsieh, Chang-Mu Sung, Betty Chien-Jung Pai, Nai-Jen Liu, and Carl PC Chen Copyright © 2016 Hao-Tsai Cheng et al. All rights reserved. Newly Emerging Parasitic Threats for Human Health: National and International Trends Thu, 04 Feb 2016 08:00:11 +0000 Lidia Chomicz, David Bruce Conn, Jacek P. Szaflik, and Beata Szostakowska Copyright © 2016 Lidia Chomicz et al. All rights reserved. Self-Perception of Swallowing-Related Problems in Laryngopharyngeal Reflux Patients Diagnosed with 24-Hour Oropharyngeal pH Monitoring Thu, 04 Feb 2016 07:40:23 +0000 Background and Objectives. Swallowing difficulty is considered one of the nonspecific symptoms that many patients with laryngopharyngeal reflux complain of. However, the relationship between laryngopharyngeal reflux and swallowing problems is not clear. The purpose of this work is to explore correlation between swallowing-related problems and laryngopharyngeal reflux (LPR) in a group of patients diagnosed with oropharyngeal pH monitoring and to study the effect of laryngopharyngeal reflux on the patients’ self-perception of swallowing problems. Methods. 44 patients complaining of reflux-related problems were included in the study. Patients underwent 24-hour oropharyngeal pH monitoring and were divided into positive and negative LPR groups based on the pH monitoring results. All patient filled out the Dysphagia Handicap Index (DHI) and Reflux Symptom Index (RSI) questionnaires. Comparison was made between the positive and negative LPR groups regarding the results of the DHI and RSI ratings. Also, correlation between DHI scores, RSI scores, and pH monitoring results was studied. Results. Significant difference was reported between positive and negative LPR groups regarding DHI scores, RSI scores, and overall rating of swallowing difficulty. There was significant correlation demonstrated between DHI scores, RSI scores, and 24-hour oropharyngeal pH results. Conclusion. Laryngopharyngeal reflux appears to have a significant impact on patients’ self-perception of swallowing problems as measured by DHI. Tamer A. Mesallam and Mohamed Farahat Copyright © 2016 Tamer A. Mesallam and Mohamed Farahat. All rights reserved. Current Applications for the Use of Extracorporeal Carbon Dioxide Removal in Critically Ill Patients Thu, 04 Feb 2016 06:43:04 +0000 Mechanical ventilation in patients with respiratory failure has been associated with secondary lung injury, termed ventilator-induced lung injury. Extracorporeal venovenous carbon dioxide removal (ECCO2R) appears to be a feasible means to facilitate more protective mechanical ventilation or potentially avoid mechanical ventilation in select patient groups. With this expanding role of ECCO2R, we aim to describe the technology and the main indications of ECCO2R. Luigi Camporota and Nicholas Barrett Copyright © 2016 Luigi Camporota and Nicholas Barrett. All rights reserved. Diagnostic Value of Magnetic Resonance Spectroscopy in Radiation Encephalopathy Induced by Radiotherapy for Patients with Nasopharyngeal Carcinoma: A Meta-Analysis Wed, 03 Feb 2016 14:20:04 +0000 In this study, articles in English and Chinese were selected from available electronic databases prior to September 2014. The metabolic concentrations and patterns of N-acetylaspartic acid (NAA), Choline (Cho), Creatine (Cr), NAA/Cr, NAA/Cho, and Cho/Cr ratios in radiotherapy-induced radiation encephalopathy by proton magnetic resonance spectroscopy were extracted. A meta-analysis was performed to quantitatively synthesize findings of these studies. Weighted mean difference (WMD) and 95% confidence intervals (95%CIs) were calculated using random or fixed effective models. Heterogeneity between studies was assessed using the Cochrane test and statistics. The results indicated that a total of 4 researches involving 214 patients met inclusion criteria. Depending on methodologies of selected studies, control groups were referred to as healthy subjects. The combined analysis revealed that there was no significant difference in value of Cr between radiotherapy group and healthy control group (WMD = −1.483, 95% CI: −67.185–64.219, ). However, there were significant difference in values of NAA (WMD = −18.227, 95%CI: −36.317–−0.137, ), Cho (WMD = 38.003, 95%CI: 5.155–70.851, ), NAA/Cr (WMD = −1.175, 95%CI: −1.563–−0.787, ), NAA/Cho (WMD = −1.108, 95%CI: −2.003–0.213, ), and Cho/Cr (WMD = −0.773, 95%CI: 0.239–1.307, ). In conclusion, MRS can be regarded as an effective and feasible imaging test for radiotherapy-induced radiation encephalopathy in NPC patients. Wang-Sheng Chen, Jian-Jun Li, Lan Hong, Zeng-Bao Xing, Fen Wang, and Chang-Qing Li Copyright © 2016 Wang-Sheng Chen et al. All rights reserved. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival Wed, 03 Feb 2016 10:49:07 +0000 In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and ). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (), female sex (), A2 fracture class (), increased operative duration (), poor reduction quality (), and suboptimal tip-apex distance of >25 mm (). Patients who had better outcome in terms of walking function were independently predicted by younger age (), higher MMSE marks (), higher MBI marks (), better premorbid walking status (), less fracture collapse (), and optimal lag screw position in centre-centre or centre-inferior position (). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. Christian Fang, Paata Gudushauri, Tak-Man Wong, Tak-Wing Lau, Terence Pun, and Frankie Leung Copyright © 2016 Christian Fang et al. All rights reserved. Prognosis Risk of Urosepsis in Critical Care Medicine: A Prospective Observational Study Wed, 03 Feb 2016 10:23:55 +0000 This study aimed to investigate the clinical features of urosepsis and to raise awareness of this problem. Of the 112 sepsis patients enrolled, 36 were identified as having urosepsis. The bacteria involved in the infection leading to urosepsis included Escherichia coli, Proteus species, Enterococcus species, Klebsiella species, other Gram-positive cocci, and Pseudomonas aeruginosa. Although the organ/system dysfunction appeared earlier in the urosepsis patients than in the other sepsis patients ( versus hours, ), the urosepsis patients presented with a better prognosis and lower 28-day mortality rate than the others (6% versus 37%). In the multivariate analysis, the type of sepsis (urosepsis, OR = 0.019, 95% CI = 0.001, 0.335, ) and SOFA score (OR = 1.896, 95% CI = 1.012, 3.554, ) remained significantly associated with the survival. The time of admission to the intensive care unit of 17 patients transferred from the Department of Urinary Surgery was significantly prolonged compared with those transferred from other departments ( versus hours, ). In conclusion, urosepsis suggested a better prognosis, but attention needs to be paid in clinical practice, especially in urinary surgery. Xin-Hua Qiang, Tie-Ou Yu, Yi-Nan Li, and Li-Xin Zhou Copyright © 2016 Xin-Hua Qiang et al. All rights reserved. Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity Wed, 03 Feb 2016 07:30:56 +0000 Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM). The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb) levels during standing during single (S-S), standing during dual (S-D), one leg standing during single (O-S), and one leg standing during dual (O-D) tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance. Hiroyuki Fujita, Kenji Kasubuchi, Satoshi Wakata, Makoto Hiyamizu, and Shu Morioka Copyright © 2016 Hiroyuki Fujita et al. All rights reserved. Analysis and Identification of Aptamer-Compound Interactions with a Maximum Relevance Minimum Redundancy and Nearest Neighbor Algorithm Wed, 03 Feb 2016 06:40:35 +0000 The development of biochemistry and molecular biology has revealed an increasingly important role of compounds in several biological processes. Like the aptamer-protein interaction, aptamer-compound interaction attracts increasing attention. However, it is time-consuming to select proper aptamers against compounds using traditional methods, such as exponential enrichment. Thus, there is an urgent need to design effective computational methods for searching effective aptamers against compounds. This study attempted to extract important features for aptamer-compound interactions using feature selection methods, such as Maximum Relevance Minimum Redundancy, as well as incremental feature selection. Each aptamer-compound pair was represented by properties derived from the aptamer and compound, including frequencies of single nucleotides and dinucleotides for the aptamer, as well as the constitutional, electrostatic, quantum-chemical, and space conformational descriptors of the compounds. As a result, some important features were obtained. To confirm the importance of the obtained features, we further discussed the associations between them and aptamer-compound interactions. Simultaneously, an optimal prediction model based on the nearest neighbor algorithm was built to identify aptamer-compound interactions, which has the potential to be a useful tool for the identification of novel aptamer-compound interactions. The program is available upon the request. ShaoPeng Wang, Yu-Hang Zhang, Jing Lu, Weiren Cui, Jerry Hu, and Yu-Dong Cai Copyright © 2016 ShaoPeng Wang et al. All rights reserved. Recombinant Brain Natriuretic Peptide for the Prevention of Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease Undergoing Nonemergent Percutaneous Coronary Intervention or Coronary Angiography: A Randomized Controlled Trial Tue, 02 Feb 2016 12:40:01 +0000 The role of brain natriuretic peptide (BNP) in the prevention of contrast-induced nephropathy (CIN) is unknown. This study aimed to investigate BNP’s effect on CIN in chronic kidney disease (CKD) patients undergoing elective percutaneous coronary intervention (PCI) or coronary angiography (CAG). The patients were randomized to BNP (0.005 μg/kg/min before contrast media (CM) exposure and saline hydration, ) or saline hydration alone (). Cystatin C, serum creatinine (SCr) levels, and estimated glomerular filtration rates (eGFR) were assessed at several time points. The primary endpoint was CIN incidence; secondary endpoint included changes in cystatin C, SCr, and eGFR. CIN incidence was significantly lower in the BNP group compared to controls (6.6% versus 16.5%, ). In addition, a more significant deterioration of eGFR, cystatin C, and SCr from 48 h to 1 week () was observed in controls compared to the BNP group. Although eGFR gradually deteriorated in both groups, a faster recovery was achieved in the BNP group. Multivariate logistic regression revealed that using >100 mL of CM (odds ratio: 4.36, ) and BNP administration (odds ratio: 0.21, ) were independently associated with CIN. Combined with hydration, exogenous BNP administration before CM effectively decreases CIN incidence in CKD patients. Jinming Liu, Yanan Xie, Fang He, Zihan Gao, Yuming Hao, Xiuguang Zu, Liang Chang, and Yongjun Li Copyright © 2016 Jinming Liu et al. All rights reserved. Development of a Murine Infection Model with Leishmania killicki, Responsible for Cutaneous Leishmaniosis in Algeria: Application in Pharmacology Tue, 02 Feb 2016 12:03:37 +0000 In Algeria, Leishmania infantum, Leishmania major, and Leishmania killicki (Leishmania tropica) are responsible for cutaneous leishmaniosis. We established a murine model of L. killicki infection to investigate its infective capacity, some immunophysiopathological aspects, and its suitability for pharmacological purposes. Following the injection of L. major or L. killicki metacyclic promastigotes in the ear dermis of BALB/c mice, the course of infection was followed. The infection with L. killicki caused slower lesion formation than with L. major. The presence of L. killicki or L. major DNA and parasites was detected in the ear dermis and in lymph nodes, spleen, and liver. Lesions induced by L. killicki were nonulcerative in their aspect, whereas those caused by L. major were highly ulcerative and necrotic, which matches well with the lesion phenotype reported in humans for L. killicki and L. major, respectively. The treatment of L. killicki lesions by injection of Glucantime® significantly reduced the lesion thickness and parasite burden. Ear dermal injection of BALB/c mice constitutes a model to study lesions physiopathology caused by L. killicki and presents interest for in vivo screening of new compounds against this pathogen, emerging in Algeria. Naouel Eddaikra, Ihcene Kherachi Djenad, Sihem Benbetka, Razika Benikhlef, Khatima Aït-Oudhia, Farida Moulti-Mati, Bruno Oury, Denis Sereno, and Zoubir Harrat Copyright © 2016 Naouel Eddaikra et al. All rights reserved. The Synthesis and Evaluations of the 68Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography Tue, 02 Feb 2016 11:50:44 +0000 Purpose. The aim of this study is to synthesize and evaluate 68Ga-labeled Lissamine Rhodamine B (LRB) as a new radiotracer for imaging MDA-MB-231 and MCF-7 cells induced tumor mice by positron emission tomography (PET). Methods. Firstly, we performed the radio synthesis and microPET imaging of 68Ga(DOTA-LRB) in athymic nude mice bearing MDA-MB-231 and MCF-7 human breast cancer xenografts. Additionally, the evaluations of 18F-fluorodeoxyglucose (FDG), as a glucose metabolism radiotracer for imaging tumors in the same xenografts, have been conducted as a comparison. Results. The radiochemical purity of 68Ga(DOTA-LRB) was >95%. MicroPET dynamic imaging revealed that the uptake of 68Ga(DOTA-LRB) was mainly in normal organs, such as kidney, heart, liver, and brain and mainly excreted from kidney. The MDA-MB-231 and MCF-7 tumors were not clearly visible in PET images at 5, 15, 30, 40, 50, and 60 min after injection of 68Ga(DOTA-LRB). The tumor uptake values of 18F-FDG were and %ID/g in MDA-MB-231 and MCF-7 tumor xenografts, respectively. Conclusions. 68Ga(DOTA-LRB) can be easily synthesized with high radiochemical purity and stability; however, it may be not an ideal PET radiotracer for imaging of MDR-positive tumors. Xuena Li, Yafu Yin, Bulin Du, Na Li, and Yaming Li Copyright © 2016 Xuena Li et al. All rights reserved. Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections Tue, 02 Feb 2016 11:28:23 +0000 Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-α and IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction. Alexandra Folk, Coralia Cotoraci, Cornel Balta, Maria Suciu, Hildegard Herman, Oana Maria Boldura, Sorina Dinescu, Lucian Paiusan, Aurel Ardelean, and Anca Hermenean Copyright © 2016 Alexandra Folk et al. All rights reserved. The Comparative Evaluation of the Antimicrobial Effect of Propolis with Chlorhexidine against Oral Pathogens: An In Vitro Study Tue, 02 Feb 2016 08:19:28 +0000 This study aimed to compare the antimicrobial effectiveness of ethanolic extract of propolis (EEP) to chlorhexidine gluconate (CHX) on planktonic Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus salivarius subsp. salivarius, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Staphylococcus aureus, Enterococcus faecalis, Actinomyces israelii, Candida albicans, and their single-species biofilms by agar dilution and broth microdilution test methods. Both agents inhibited the growth of all planktonic species. On the other hand, CHX exhibited lower minimum bactericidal concentrations than EEP against biofilms of A. actinomycetemcomitans, S. aureus, and E. faecalis whereas EEP yielded a better result against Lactobacilli and P. intermedia. The bactericidal and fungicidal concentrations of both agents were found to be equal against biofilms of Streptecocci, P. gingivalis, A. israelii, and C. albicans. The results of this study revealed that propolis was more effective in inhibiting Gram-positive bacteria than the Gram-negative bacteria in their planktonic state and it was suggested that EEP could be as effective as CHX on oral microorganisms in their biofilm state. A. Eralp Akca, Gülçin Akca, Fulya Toksoy Topçu, Enis Macit, Levent Pikdöken, and I. Şerif Özgen Copyright © 2016 A. Eralp Akca et al. All rights reserved. Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3 Signaling Pathway Mon, 01 Feb 2016 14:03:15 +0000 Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity. Guorong Tao, Qingsheng Xue, Yan Luo, Guohui Li, Yimeng Xia, and Buwei Yu Copyright © 2016 Guorong Tao et al. All rights reserved. A CRISPR-Based Toolbox for Studying T Cell Signal Transduction Mon, 01 Feb 2016 13:03:59 +0000 CRISPR/Cas9 system is a powerful technology to perform genome editing in a variety of cell types. To facilitate the application of Cas9 in mapping T cell signaling pathways, we generated a toolbox for large-scale genetic screens in human Jurkat T cells. The toolbox has three different Jurkat cell lines expressing distinct Cas9 variants, including wild-type Cas9, dCas9-KRAB, and sunCas9. We demonstrated that the toolbox allows us to rapidly disrupt endogenous gene expression at the DNA level and to efficiently repress or activate gene expression at the transcriptional level. The toolbox, in combination with multiple currently existing genome-wide sgRNA libraries, will be useful to systematically investigate T cell signal transduction using both loss-of-function and gain-of-function genetic screens. Shen Chi, Arthur Weiss, and Haopeng Wang Copyright © 2016 Shen Chi et al. All rights reserved. Circulating Long Noncoding RNA UCA1 as a Novel Biomarker of Acute Myocardial Infarction Mon, 01 Feb 2016 13:02:41 +0000 Acute myocardial infarction (AMI) is the most serious cardiovascular disease with high morbidity and mortality. Recent studies have showed that long noncoding RNAs (lnc RNA) play important roles in pathophysiology of cardiovascular diseases, but the investigations are still in their infancy. An lnc RNA named urothelial carcinoma-associated 1 (UCA1) is found in tumors such as bladder cancers and lung cancer. And the UCA1 could be as a predictive biomarker for bladder cancer in urine samples or lung cancer in plasma, respectively. In normal states, UCA1 is specifically expressed in heart of adult, indicating that UCA1 might be as a biomarker for heart diseases such as AMI. To test the speculation, we detect the level of UCA1 in plasma of AMI patients and health control using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, we also test the level of miR-1 as it is reported to regulate the expression of UCA1. The results show that the level of plasma UCA1 is decreased at the early state of AMI patients and increased at day 3 after AMI. In addition, the UCA1 alteration is inversely associated with the expression of miR-1. These findings indicate that the circulating UCA1 could be used as a promising novel biomarker for the diagnosis and/or prognosis of AMI. Youyou Yan, Bin Zhang, Ning Liu, Chao Qi, Yanlong Xiao, Xin Tian, Tianyi Li, and Bin Liu Copyright © 2016 Youyou Yan et al. All rights reserved. Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis Mon, 01 Feb 2016 09:58:50 +0000 This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22–4.88] () for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60–0.69] (). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65–0.86] () and 0.80 [95% CI: 0.70–0.90] (), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM. Xiaoxue Wang, Yan Li, and Xiaojing Yan Copyright © 2016 Xiaoxue Wang et al. All rights reserved. Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice Sun, 31 Jan 2016 16:56:22 +0000 AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the “multiple hit hypothesis” of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis. Wael N. Sayej, Paul R. Knight III, Weidun Alan Guo, Barbara Mullan, Patricia J. Ohtake, Bruce A. Davidson, Abdur Khan, Robert D. Baker, and Susan S. Baker Copyright © 2016 Wael N. Sayej et al. All rights reserved. Behavioral Periodicity Detection from 24 h Wrist Accelerometry and Associations with Cardiometabolic Risk and Health-Related Quality of Life Sun, 31 Jan 2016 13:34:57 +0000 Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants (17 men, 3 women, aged 35–65) continuously for (range: 13.9 to 102.0) consecutive days. Cardiometabolic risk biomarkers and health-related quality of life metrics were assessed at baseline. Periodograms were constructed to determine patterns emergent from the accelerometer data. Periodicity strength was calculated using circular autocorrelations for time-lagged windows. The most notable periodicity was at 24 h, indicating a circadian rest-activity cycle; however, its strength varied significantly across participants. Periodicity strength was most consistently associated with LDL-cholesterol (’s = 0.40–0.79, ’s < 0.05) and triglycerides (’s = 0.68–0.86, ’s < 0.05) but also associated with hs-CRP and health-related quality of life, even after adjusting for demographics and self-rated physical activity and insomnia symptoms. Our framework demonstrates a new method for characterizing behavior patterns longitudinally which captures relationships between 24 h accelerometry data and health outcomes. Matthew P. Buman, Feiyan Hu, Eamonn Newman, Alan F. Smeaton, and Dana R. Epstein Copyright © 2016 Matthew P. Buman et al. All rights reserved.