BioMed Research International The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Crystal Structure of the N-Terminal RNA Recognition Motif of mRNA Decay Regulator AUF1 Wed, 29 Jun 2016 06:02:26 +0000 AU-rich element binding/degradation factor 1 (AUF1) plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE) in the 3′-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM) and a Gln- (Q-) rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs. However, only N-terminal RRM (RRM1) was crystallized and its structure was determined at 1.7 Å resolution. It appears that the RRM1 and RRM2 separated before crystallization. To demonstrate which factors affect the separate RRM1-2, we performed limited proteolysis using trypsin. The results indicated that the intact proteins were cleaved by unknown proteases that were associated with them prior to crystallization. In comparison with each of the monomers, the conformations of the β2-β3 loops were highly variable. Furthermore, a comparison with the RRM1-2 structures of HuR and hnRNP A1 revealed that a dimer of RRM1 could be one of the possible conformations of RRM1-2. Our data may provide a guidance for further structural investigations of AUF1 tandem RRM repeat and its mode of ARE binding. Young Jun Choi, Je-Hyun Yoon, and Jeong Ho Chang Copyright © 2016 Young Jun Choi et al. All rights reserved. Fretting and Corrosion in Modular Shoulder Arthroplasty: A Retrieval Analysis Tue, 28 Jun 2016 16:00:28 +0000 Tribocorrosion in taper junctions of retrieved anatomic shoulder arthroplasty implants was evaluated. A comparison of the tribocorrosion between cobalt-chromium and titanium alloy stems was conducted and the observations were correlated with the individual’s clinical data. Adverse effects caused by metal debris and subsequent elevated serum metal ion levels are frequently reported in total hip arthroplasty. In total shoulder arthroplasty, to date only a small number of retrieval analyses are available and even fewer address the issue of tribocorrosion at the taper junctions. A total of 36 retrieved hemiarthroplasties and total shoulder arthroplasties were assessed using the modified Goldberg score. The prevalence of fretting and corrosion was confirmed in this cohort. Titanium stems seem to be more susceptible to damage caused by tribocorrosion than cobalt-chromium stems. Furthermore, stemless designs offered less tribocorrosion at the taper junction than stemmed designs. A weak correlation between time to revision and increased levels of tribocorrosion was seen. Whether or not tribocorrosion can lead to adverse clinical reactions and causes failure of shoulder arthroplasties remains to be examined. Johannes A. Eckert, Ulrike Mueller, Sebastian Jaeger, Benjamin Panzram, and J. Philippe Kretzer Copyright © 2016 Johannes A. Eckert et al. All rights reserved. Geographical Distribution and New Situation of Leishmania Species after the Control of Cutaneous Leishmaniasis Foci in Errachidia Province, Morocco, in 2014 Tue, 28 Jun 2016 15:40:37 +0000 In Errachidia province, the incidence of cutaneous leishmaniasis (CL) has increased over the past decade and it was higher in 2010 (860.34 per 100,000 inhabitants), with 3445 cases. The number of cases declined sharply and decreased from 3445 cases in 2010 to 8 cases in 2014 following the control action plan interventions. The total of patients was diagnosed only on clinical basis and the lesions were considered caused by L. major. The epidemiological study was conducted between 2001 and 2014 and the molecular detection of CL was studied to identify the circulating parasite species in this province by using the ITS1-PCR-RFLP methods. In 2010, the molecular identification of 11 samples revealed the presence of L. major in the most affected circles: Goulmima, Er-Rissani, and Errachidia. In 2014 the molecular characterization of 7 among 8 cases reported in this year showed the presence of L. tropica in Errachidia circle. This is the first molecular identification of L. tropica in Errachidia province. The detection of this species after the intensified control measures strategies suggests that it was probably dissipated through the dominance of L. major. El Alem Mohamed Mahmoud, Sebti Faiza, Med Lemine, Chichaoui Smaine, El Bachir Adlaoui, Habbari Khalid, Sadak Abderrahim, and Fellah Hajiba Copyright © 2016 El Alem Mohamed Mahmoud et al. All rights reserved. Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments Tue, 28 Jun 2016 15:24:43 +0000 Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged. Martin Sauer, Jens Altrichter, Cristof Haubner, Annette Pertschy, Thomas Wild, Fanny Doß, Thomas Mencke, Maren Thomsen, Johannes Ehler, Jörg Henschel, Sandra Doß, Stephanie Koch, Georg Richter, Gabriele Nöldge-Schomburg, and Steffen R. Mitzner Copyright © 2016 Martin Sauer et al. All rights reserved. Relation between Resting State Front-Parietal EEG Coherence and Executive Function in Parkinson’s Disease Tue, 28 Jun 2016 15:05:15 +0000 Objective. To assess the relation between executive dysfunction (ED) in Parkinson’s disease (PD) and resting state functional connectivity evaluated using electroencephalography (EEG) coherence. Methods. Sixty-eight nondemented sporadic PD patients were assessed using the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to evaluate executive function. EEG coherence in the left frontoparietal electrode pair (F3-P3) and the right frontoparietal electrode pair (F4-P4) was analyzed in the alpha and theta range. The BADS scores were compared across the coherence groups, and the multiple logistic regression analysis was performed to assess the contribution of confounders. Results. The standardized BADS score was significantly lower in the low F3-P3 coherence group in the alpha range (Mann-Whitney test, ), though there was no difference between F4-P4 coherence group in the alpha range, F3-P3, and F4-P4 coherence groups in the theta range and the standardized BADS score. The multiple logistic regression analysis revealed the significant relation between the F3-P3 coherence group in alpha range and age-controlled standardized BADS score (, 95% CI = 1.002–1.062). Conclusion. The decrease in resting state functional connectivity between the frontal and parietal cortices especially in the left side is related to ED in PD. Hiroko Teramoto, Akihiko Morita, Satoko Ninomiya, Takayoshi Akimoto, Hiroshi Shiota, and Satoshi Kamei Copyright © 2016 Hiroko Teramoto et al. All rights reserved. Minimally Invasive Transforaminal Lumbar Interbody Fusion at L5-S1 through a Unilateral Approach: Technical Feasibility and Outcomes Tue, 28 Jun 2016 11:55:03 +0000 Background. Minimally invasive spinal transforaminal lumbar interbody fusion (MIS-TLIF) at L5-S1 is technically more demanding than it is at other levels because of the anatomical and biomechanical traits. Objective. To determine the clinical and radiological outcomes of MIS-TLIF for treatment of single-level spinal stenosis low-grade isthmic or degenerative spondylolisthesis at L5-S1. Methods. Radiological data and electronic medical records of patients who underwent MIS-TLIF between May 2012 and December 2014 were reviewed. Fusion rate, cage position, disc height (DH), disc angle (DA), disc slope angle, segmental lordotic angle (SLA), lumbar lordotic angle (LLA), and pelvic parameters were assessed. For functional assessment, the visual analogue scale (VAS), Oswestry disability index (ODI), and patient satisfaction rate (PSR) were utilized. Results. A total of 21 levels in 21 patients were studied. DH, DA, SLA, and LLA had increased from their preoperative measures at the final follow-up. Fusion rate was 86.7% (18/21) at 12 months’ follow-up. The most common cage position was anteromedial (15/21). The mean VAS scores for back and leg pain mean ODI scores improved significantly at the final follow-up. PSR was 88%. Cage subsidence was observed in 33.3% (7/21). Conclusions. The clinical and radiologic outcomes after MIS-TLIF at L5-S1 in patients with spinal stenosis or spondylolisthesis are generally favorable. Won-Suh Choi, Jin-Sung Kim, Kyeong-Sik Ryu, Jung-Woo Hur, and Ji-Hoon Seong Copyright © 2016 Won-Suh Choi et al. All rights reserved. Evaluation of Potential Clinical Surrogate Markers of a Trauma Induced Alteration of Clotting Factor Activities Tue, 28 Jun 2016 07:00:07 +0000 Objective. The aim of this study was to identify routinely available clinical surrogate markers for potential clotting factor alterations following multiple trauma. Methods. In 68 patients admitted directly from the scene of the accident, all soluble clotting factors were analyzed and clinical data was collected prospectively. Ten healthy subjects served as control group. Results. Patients showed reduced activities of clotting factors II, V, VII, and X and calcium levels (all to 0.01). Levels of hemoglobin and base deficit correlated moderately to highly with the activities of a number of clotting factors. Nonsurvivors and patients who needed preclinical intubation or hemostatic therapy showed significantly reduced factor activities at admission. In contrast, factor VIII activity was markedly elevated after injury in general (), but reduced in nonsurvivors (). Conclusions. Multiple trauma causes an early reduction of the activities of nearly all soluble clotting factors in general. Initial hemoglobin and, with certain qualifications, base deficit levels demonstrated a potential value in detecting those underlying clotting factor deficiencies. Nevertheless, their role as triggers of a hemostatic therapy as well as the observed response of factor VIII to multiple trauma and also its potential prognostic value needs further evaluation. Manuel Burggraf, Arzu Payas, Carsten Schoeneberg, Alexander Wegner, Max Daniel Kauther, and Sven Lendemans Copyright © 2016 Manuel Burggraf et al. All rights reserved. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data Mon, 27 Jun 2016 16:15:54 +0000 Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer. Tianjiao Zhang, Yang Hu, Xiaoliang Wu, Rui Ma, Qinghua Jiang, and Yadong Wang Copyright © 2016 Tianjiao Zhang et al. All rights reserved. Conjugated Linoleic Acid Production by Bifidobacteria: Screening, Kinetic, and Composition Mon, 27 Jun 2016 14:27:11 +0000 Conjugated linoleic acids (CLA) are positional and geometric isomers of linoleic acid involved in a number of health aspects. In humans, CLA production is performed by gut microbiota, including some species of potential probiotic bifidobacteria. 128 strains of 31 Bifidobacterium species were screened with a spectrophotometric assay to identify novel CLA producers. Most species were nonproducers, while producers belonged to B. breve and B. pseudocatenulatum. GC-MS revealed that CLA producer strains yielded 9cis,11trans-CLA and 9trans,11trans-CLA, without any production of other isomers. Hydroxylated forms of LA were absent in producer strains, suggesting that the myosin-cross-reactive antigen (MCRA) protein that exerts hydratase activity is not involved in LA isomerization. Moreover, both CLA producer and nonproducer species bear a MCRA homologue. The strain B. breve WC 0421 was the best CLA producer, converting LA into 68.8% 9cis,11trans-CLA and 25.1% 9trans,11trans-CLA. Production occurred mostly during the lag and the exponential phase. For the first time, production and incorporation of CLA in biomass were assessed. B. breve WC 0421 stored CLA in the form of free fatty acids, without changing the composition of the esterified fatty acids, which mainly occurred in the plasmatic membrane. Stefano Raimondi, Alberto Amaretti, Alan Leonardi, Andrea Quartieri, Caterina Gozzoli, and Maddalena Rossi Copyright © 2016 Stefano Raimondi et al. All rights reserved. CX3CL1/CX3CR1 in Alzheimer’s Disease: A Target for Neuroprotection Mon, 27 Jun 2016 14:23:45 +0000 CX3C chemokine ligand 1 (CX3CL1) is an intriguing chemokine belonging to the CX3C family. CX3CL1 is secreted by neurons and plays an important role in modulating glial activation in the central nervous system after binding to its sole receptor CX3CR1 which mainly is expressed on microglia. Emerging data highlights the beneficial potential of CX3CL1-CX3CR1 in the pathogenesis of Alzheimer’s disease (AD), a common progressive neurodegenerative disease, and in the progression of which neuroinflammation plays a vital role. Even so, the importance of CX3CL1/CX3CR1 in AD is still controversial and needs further clarification. In this review, we make an attempt to present a concise map of CX3CL1-CX3CR1 associated with AD to find biomarkers for early diagnosis or therapeutic interventions. Peiqing Chen, Wenjuan Zhao, Yanjie Guo, Juan Xu, and Ming Yin Copyright © 2016 Peiqing Chen et al. All rights reserved. Feasibility and Safety of Absorbable Knotless Wound Closure Device in Laparoscopic Myomectomy Mon, 27 Jun 2016 14:13:41 +0000 Purpose. Myomectomy has been performed through laparoscopy. Suturing is known as rate-limiting step in laparoscopic myomectomy. The present study was aimed at comparing the clinical outcomes of absorbable knotless wound closure device with the results of conventional suturing. Methods. This prospective study included 62 women who underwent laparoscopic myomectomy at Taipei City Hospital, Zhongxiao Branch, from January 2010 through to August 2012. The patients were randomized into two groups according to suturing materials, the knotless group and the 2-0 Vicryl suture group. Patient demographics, overall operative time, and intraoperative blood loss were compared between two groups. Results. Demographic characteristics and laboratory variables before surgery were comparable. Operative time was significantly shorter in knotless group compared with that in 2-0 Vicryl suture group ( versus minutes; ). The results revealed a significant difference in intraoperative blood loss between two groups (knotless versus 2-0 Vicryl: versus ). Use of absorbable knotless wound closure device was associated with greater hemostasis compared with that of 2-0 Vicryl. During a 2-year follow-up period, 12 patients (46.2%) from the group with absorbable knotless wound closure device and 14 patients (38.9%) from 2-0 Vicryl suture group became pregnant. Conclusion. Closure of myometrium using absorbable knotless wound closure device after laparoscopic myomectomy resulted in a shorter operative time and less blood loss. Chying-Chyuan Chan and Ching-Yu Lee Copyright © 2016 Chying-Chyuan Chan and Ching-Yu Lee. All rights reserved. Fermentation Quality and Additives: A Case of Rice Straw Silage Mon, 27 Jun 2016 12:25:20 +0000 Rice cultivation generates large amount of crop residues of which only 20% are utilized for industrial and domestic purposes. In most developing countries especially southeast Asia, rice straw is used as part of feeding ingredients for the ruminants. However, due to its low protein content and high level of lignin and silica, there is limitation to its digestibility and nutritional value. To utilize this crop residue judiciously, there is a need for improvement of its nutritive value to promote its utilization through ensiling. Understanding the fundamental principle of ensiling is a prerequisite for successful silage product. Prominent factors influencing quality of silage product include water soluble carbohydrates, natural microbial population, and harvesting conditions of the forage. Additives are used to control the fermentation processes to enhance nutrient recovery and improve silage stability. This review emphasizes some practical aspects of silage processing and the use of additives for improvement of fermentation quality of rice straw. Yusuff Oladosu, Mohd Y. Rafii, Norhani Abdullah, Usman Magaji, Ghazali Hussin, Asfaliza Ramli, and Gous Miah Copyright © 2016 Yusuff Oladosu et al. All rights reserved. MicroRNAs as Salivary Markers for Periodontal Diseases: A New Diagnostic Approach? Mon, 27 Jun 2016 12:07:52 +0000 The aim of this review is to discuss current findings regarding the roles of miRNAs in periodontal diseases and the potential use of saliva as a diagnostic medium for corresponding miRNA investigations. For periodontal disease, investigations have been restricted to tissue samples and five miRNAs, that is, miR-142-3p, miR-146a, miR-155, miR-203, and miR-223, were repeatedly validated in vivo and in vitro by different validation methods. Particularly noticeable are the small sample sizes, different internal controls, and different case definitions of periodontitis in in vivo studies. Beside of that, the validated miRNAs are associated with inflammation and therefore with various diseases. Furthermore, several studies successfully explored the use of salivary miRNA species for the diagnosis of oral cancer. Different cancer types were investigated and heterogeneous methodology was used; moreover, no overlap of results was found. In conclusion, five miRNAs have consistently been reported for periodontitis; however, their disease specificity, detectability, and expression in saliva and their importance as noninvasive markers are questionable. In principle, a salivary miRNA diagnostic method seems feasible. However, standardized criteria and protocols for preanalytics, measurements, and analysis should be established to obtain comparable results across different studies. Gerhard Schmalz, Simin Li, Ralph Burkhardt, Sven Rinke, Felix Krause, Rainer Haak, and Dirk Ziebolz Copyright © 2016 Gerhard Schmalz et al. All rights reserved. Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk? Mon, 27 Jun 2016 09:36:31 +0000 Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors. Sujani Yadlapati and Petros Efthimiou Copyright © 2016 Sujani Yadlapati and Petros Efthimiou. All rights reserved. Exploration of the Dietary and Lifestyle Behaviors and Weight Status and Their Self-Perceptions among Health Sciences University Students in North Lebanon Mon, 27 Jun 2016 07:02:25 +0000 University students may experience significant environmental changes that exert a negative influence on the quality of their diet and lifestyle. There is scarcity of data concerning the dietary and lifestyle behaviors and weight status of students in the health field in North Lebanon. To investigate these data, a cross-sectional survey was conducted including 369 health sciences students aged 18–25 chosen from four public and private universities in North Lebanon. Data were collected using a standardized interview questionnaire to determine sociodemographic, dietary, and lifestyle behaviors, appetite changes, stress related dietary behaviors, and food cravings, as well as self-perceptions of dietary adequacy, physical activity levels, and weight status. Body mass index was assessed. Results had revealed significant differences in some of the dietary consumption patterns and weight status among seniors compared to juniors. However, the overall prevalence of overweight and obesity recorded 32.2% and the dietary consumption patterns fall below recommended levels. Multivariate regression analysis showed that parental obesity, comfort eating, increased appetite, food cravings, and stressful eating were associated with increased risk of obesity while a healthy diet score was associated with decreased risk. The study’s findings call for tailoring culture specific intervention programs which enable students to improve their dietary and lifestyle behaviors and control stress. Germine El-Kassas and Fouad Ziade Copyright © 2016 Germine El-Kassas and Fouad Ziade. All rights reserved. Fragility Fracture Care and Orthogeriatric Comanagement Mon, 27 Jun 2016 06:21:48 +0000 Christian Kammerlander, Hitendra K. Doshi, Wolfgang Böcker, and Markus Gosch Copyright © 2016 Christian Kammerlander et al. All rights reserved. The Effect of Teriparatide on Fracture Healing of Osteoporotic Patients: A Meta-Analysis of Randomized Controlled Trials Sun, 26 Jun 2016 13:30:09 +0000 Purpose. This meta-analysis is to assess the effectiveness of teriparatide in fracture healing and clinical function improvement of the osteoporotic patients. Methods. We searched PubMed, Embase, Web of Science, and the Cochrane databases for randomized and quasi-randomized controlled trials comparing teriparatide to placebo, no treatment, or comparator interventions in the osteoporotic patients. Results. Five studies with 251 patients were included. Patients treated with teriparatide therapy had a significant shorter radiological fracture healing time compared with those in the control group (mean difference [MD] −4.54 days, 95% confidence interval [CI] −8.80 to −0.28). Stratified analysis showed that lower limb group had significant shorter healing time (MD −6.24 days, 95% CI −7.20 to −5.29), but upper limb group did not (MD −1 days, 95% CI −2.02 to 0.2). Patients treated with teriparatide therapy showed better functional outcome than those in the control group (standardized mean difference [SMD] −1.02, 95% CI −1.81 to −0.22). Patients with therapy duration over 4 weeks would have better functional outcome (SMD −1.68, 95% CI −2.07 to −1.29). Conclusions. Teriparatide is effective in accelerating fracture healing and improving functional outcome of osteoporotic women. However, more clinical studies are warranted in order to determine whether the results are applicable to males and the clinical indications for teriparatide after osteoporotic fractures. Shenghan Lou, Houchen Lv, Guoqi Wang, Licheng Zhang, Ming Li, Zhirui Li, Lihai Zhang, and Peifu Tang Copyright © 2016 Shenghan Lou et al. All rights reserved. MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis Sun, 26 Jun 2016 13:28:32 +0000 MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway. Ying Chen, Pei-Feng Xian, Lu Yang, and Sheng-Xu Wang Copyright © 2016 Ying Chen et al. All rights reserved. Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease Sun, 26 Jun 2016 13:27:50 +0000 The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid. Francesco Panza, Vincenzo Solfrizzi, Davide Seripa, Bruno P. Imbimbo, Madia Lozupone, Andrea Santamato, Chiara Zecca, Maria Rosaria Barulli, Antonello Bellomo, Alberto Pilotto, Antonio Daniele, Antonio Greco, and Giancarlo Logroscino Copyright © 2016 Francesco Panza et al. All rights reserved. Effect of Water-Glass Coating on HA and HA-TCP Samples for MSCs Adhesion, Proliferation, and Differentiation Sun, 26 Jun 2016 12:34:37 +0000 Ca-P and silicon based materials have become very popular as bone tissue engineering materials. In this study, water-glass (also known as sodium silicate glass) was coated on sintered hydroxyapatite (HA) and HA-TCP (TCP stands for tricalcium phosphate) samples and subsequently heat-treated at 600°C for 2 hrs. X-rays diffraction showed the presence of β- and α-TCP phases along with HA in the HA-TCP samples. Samples without coating, with water-glass coating, and heat-treated after water-glass coating were used to observe the adhesion and proliferation response of bone marrow derived-mesenchymal stem cells (MSCs). Cell culture was carried out for 4 hrs, 1 day, and 7 days. Interestingly, all samples showed similar response for cell adhesion and proliferation up to 7-day culture but fibronectin, E-cadherin, and osteogenic differentiation related genes (osteocalcin and osteopontin) were significantly induced in heat-treated water-glass coated HA-TCP samples. A water-glass coating on Ca-P samples was not found to influence the cell proliferation response significantly but activated some extracellular matrix genes and induced osteogenic differentiation in the MSCs. Indu Bajpai, Duk Yeon Kim, Jung Kyong-Jin, In-Hwan Song, and Sukyoung Kim Copyright © 2016 Indu Bajpai et al. All rights reserved. Phytochemical, Antimicrobial, and Toxicological Evaluation of Traditional Herbs Used to Treat Sore Throat Sun, 26 Jun 2016 11:28:35 +0000 The in vitro antibacterial activities of 29 traditional medicinal plants used in respiratory ailments were assessed on multidrug resistant Gram-positive and Gram-negative bacteria isolated from the sore throat patients and two reference strains. The methanolic, n-hexane, and aqueous extracts were screened by the agar well diffusion assay. Bioactive fractions of effective extracts were identified on TLC coupled with bioautography, while their toxicity was determined using haemolytic assay against human erythrocytes. Qualitative and quantitative phytochemical analysis of effective extracts was also performed. Methanolic extract of 18 plants showed antimicrobial activity against test strains. Adhatoda vasica (ZI = 17–21 mm, MIC: 7.12–62.5 μg/mL), Althaea officinalis (ZI = 16–20 mm, MIC: 15.62–31.25 μg/mL), Cordia latifolia (ZI = 16–20 mm, MIC: 12.62–62.5 μg/mL), Origanum vulgare (ZI = 20–22 mm, MIC: 3–15.62 μg/mL), Thymus vulgaris (ZI = 21–25 mm, MIC: 7.81–31.25 μg/mL), and Ziziphus jujuba (ZI = 14–20 mm, MIC: 7.81–31.25 μg/mL) showed significant antibacterial activity. Alkaloid fractions of Adhatoda vasica, Cordia latifolia, and Origanum vulgare and flavonoid fraction of the Althaea officinalis, Origanum vulgare, Thymus Vulgaris, and Ziziphus jujuba exhibited antimicrobial activity. Effective plant extracts show 0.93–0.7% erythrocyte haemolysis. The results obtained from this study provide a scientific rationale for the traditional use of these herbs and laid the basis for future studies to explore novel antimicrobial compounds. Arifa Mehreen, Muzzamil Waheed, Iram Liaqat, and Najma Arshad Copyright © 2016 Arifa Mehreen et al. All rights reserved. High Expression of PTGR1 Promotes NSCLC Cell Growth via Positive Regulation of Cyclin-Dependent Protein Kinase Complex Sun, 26 Jun 2016 07:54:13 +0000 Lung cancer has been the most common cancer and the main cause of cancer-related deaths worldwide for several decades. PTGR1 (prostaglandin reductase 1), as a bifunctional enzyme, has been involved in the occurrence and progression of cancer. However, its impact on human lung cancer is rarely reported. In this study, we found that PTGR1 was overexpressed in lung cancer based on the analyses of Oncomine. Moreover, lentivirus-mediated shRNA knockdown of PTGR1 reduced cell viability in human lung carcinoma cells 95D and A549 by MTT and colony formation assay. PTGR1 depletion led to G2/M phase cell cycle arrest and increased the proportion of apoptotic cells in 95D cells by flow cytometry. Furthermore, silencing PTGR1 in 95D cells resulted in decreased levels of cyclin-dependent protein kinase complex (CDK1, CDK2, cyclin A2, and cyclin B1) by western blotting and then PTGR1 is positively correlated with cyclin-dependent protein by using the data mining of the Oncomine database. Therefore, our findings suggest that PTGR1 may play a role in lung carcinogenesis through regulating cell proliferation and is a potential new therapeutic strategy for lung cancer. Xianping Huang, Weihe Zhou, Yuefeng Zhang, and Yong Liu Copyright © 2016 Xianping Huang et al. All rights reserved. Focal Segmental Glomerulosclerosis: Genetics, Mechanism, and Therapies Sun, 26 Jun 2016 07:54:06 +0000 Andreas Kronbichler, Jun Oh, Björn Meijers, and Jae Il Shin Copyright © 2016 Andreas Kronbichler et al. All rights reserved. Glia-Neuron Interactions in the Retina Can Be Studied in Cocultures of Müller Cells and Retinal Ganglion Cells Sun, 26 Jun 2016 06:11:11 +0000 Glia-neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing energy sources. The aim was to explore the impact of Müller cells on RGC survival. To investigate the Müller cell/RGC interactions we developed a coculture model, in which primary Müller cells were grown in inserts on top of pure primary RGC cultures. The impact of starvation and mitochondrial inhibition on the Müller cell ability to protect RGCs was studied. Moreover, the ability of Müller cells to remove glutamate from the extracellular space was investigated. RGC survival was evaluated by cell viability assays and glutamate uptake was assessed by kinetic uptake assays. We demonstrated a significantly increased RGC survival in presence of untreated and prestarved Müller cells. Additionally, prestarved Müller cells significantly increased RGC survival after mitochondrial inhibition. Finally, we revealed a significantly increased ability to take up glutamate in starved Müller cells. Overall, our study confirms essential roles of Müller cells in RGC survival. We suggest that targeting Müller cell function could have potential for future treatment strategies to prevent blinding neurodegenerative retinal diseases. D. M. Skytt, A. K. Toft-Kehler, C. T. Brændstrup, S. Cejvanovic, I. S. Gurubaran, L. H. Bergersen, and M. Kolko Copyright © 2016 D. M. Skytt et al. All rights reserved. Comparative Efficacy of the Air-Q Intubating Laryngeal Airway during General Anesthesia in Pediatric Patients: A Systematic Review and Meta-Analysis Thu, 23 Jun 2016 14:54:09 +0000 Air-Q® (air-Q) is a supraglottic airway device which can be used as a guidance of intubation in pediatric as well as in adult patients. We evaluated the efficacy and safety of air-Q compared to other airway devices during general anesthesia in pediatric patients by conducting a systematic review and meta-analysis. A total of 10 studies including 789 patients were included in the final analysis. Compared with other supraglottic airway devices, air-Q showed no evidence for a difference in leakage pressure and insertion time. The ease of insertion was significantly lower than other supraglottic airway devices. The success rate of intubation was significantly lower than other airway devices. However, fiberoptic view was better through the air-Q than other supraglottic airway devices. Therefore, air-Q could be a safe substitute for other airway devices and may provide better fiberoptic bronchoscopic view. Eun Jin Ahn, Geun Joo Choi, Hyun Kang, Chong Wha Baek, Yong Hun Jung, Young Cheol Woo, and Si Ra Bang Copyright © 2016 Eun Jin Ahn et al. All rights reserved. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery Thu, 23 Jun 2016 12:56:43 +0000 The incidence of acute kidney injury after cardiac surgery (CS-AKI) ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI. Su Rin Shin, Won Ho Kim, Dong Joon Kim, Il-Woo Shin, and Ju-Tae Sohn Copyright © 2016 Su Rin Shin et al. All rights reserved. Cloning and Expression Analysis of One Gamma-Glutamylcysteine Synthetase Gene (Hbγ-ECS1) in Latex Production in Hevea brasiliensis Thu, 23 Jun 2016 10:41:09 +0000 Rubber tree is a major commercial source of natural rubber. Latex coagulation is delayed by thiols, which belong to the important type of antioxidants in laticifer submembrane, and is composed of glutathione (GSH), cysteine, and methionine. The rate-limiting enzyme, γ-ECS, plays an important role in regulating the biosynthesis of glutathione under any environment conditions. To understand the relation between γ-ECS and thiols and to correlate latex flow with one-time tapping and continuous tapping, we cloned and derived the full length of one γ-ECS from rubber tree latex (Hbγ-ECS1). According to qPCR analysis, the expression levels of Hbγ-ECS1 were induced by tapping and Ethrel stimulation, and the expression was related to thiols content in the latex. Continuous tapping induced injury, and the expression of HbγECS1 increased with routine tapping and Ethrel-stimulation tapping (more intensive tapping). According to expression in long-term flowing latex, the gene was related to the duration of latex flow. HbγECS1 was expressed in E. coli Rosetta using pET-sumo as an expression vector and the recombinant enzyme was purified; then we achieved 0.827 U/mg specific activity and about 66 kDa molecular weight. The present study can help us understand the complex role of Hbγ-ECS in thiols biosynthesis, which is influenced by tapping. Wei Fang, Luo Shi Qiao, Wu Ming, Qiu Jian, Yang Wen Feng, Gao Hong Hua, and Xiao Xian Zhou Copyright © 2016 Wei Fang et al. All rights reserved. Acoustic Cavitation Enhances Focused Ultrasound Ablation with Phase-Shift Inorganic Perfluorohexane Nanoemulsions: An In Vitro Study Using a Clinical Device Thu, 23 Jun 2016 07:12:17 +0000 Purpose. To investigate whether acoustic cavitation could increase the evaporation of a phase-shift inorganic perfluorohexane (PFH) nanoemulsion and enhance high intensity focused ultrasound (HIFU) ablation. Materials and Methods. PFH was encapsulated by mesoporous silica nanocapsule (MSNC) to form a nanometer-sized droplet (MSNC-PFH). It was added to a tissue-mimicking phantom, whereas phosphate buffered saline (PBS) was added as a control (PBS-control). HIFU ( W,  s) exposures were performed in both phantoms with various duty cycles (DC). US images, temperature, and cavitation emissions were recorded during HIFU exposure. HIFU-induced lesions were measured and calculated. Results. Compared to PBS-control, MSNC-PFH nanoemulsion could significantly increase the volume of HIFU-induced lesion (). Peak temperatures were 78.16 ± 5.64°C at a DC of 100%, 70.17 ± 6.43°C at 10%, 53.17 ± 4.54°C at 5%, and 42.00 ± 5.55°C at 2%, respectively. Inertial cavitation was much stronger in the pulsed-HIFU than that in the continuous-wave HIFU exposure. Compared to 100%-DC exposure, the mean volume of lesion induced by 5 s exposure at 10%-DC was significantly larger, but smaller at 2%-DC. Conclusions. MSNC-PFH nanoemulsion can significantly enhance HIFU ablation. Appropriate pulsed-HIFU exposure could significantly increase the volume of lesion and reduce total US energy required for HIFU ablation. Lu-Yan Zhao, Jian-Zhong Zou, Zong-Gui Chen, Shan Liu, Jiao Jiao, and Feng Wu Copyright © 2016 Lu-Yan Zhao et al. All rights reserved. A Metric on the Space of Partly Reduced Phylogenetic Networks Thu, 23 Jun 2016 06:48:16 +0000 Phylogenetic networks are a generalization of phylogenetic trees that allow for the representation of evolutionary events acting at the population level, such as recombination between genes, hybridization between lineages, and horizontal gene transfer. The researchers have designed several measures for computing the dissimilarity between two phylogenetic networks, and each measure has been proven to be a metric on a special kind of phylogenetic networks. However, none of the existing measures is a metric on the space of partly reduced phylogenetic networks. In this paper, we provide a metric, -distance, on the space of partly reduced phylogenetic networks, which is polynomial-time computable. Juan Wang Copyright © 2016 Juan Wang. All rights reserved. A Comparative Study of Microleakage on Dental Surfaces Bonded with Three Self-Etch Adhesive Systems Treated with the Er:YAG Laser and Bur Wed, 22 Jun 2016 14:24:41 +0000 Aim. This study sought to compare the microleakage of three adhesive systems in the context of Erbium-YAG laser and diamond bur cavity procedures. Cavities were restored with composite resin. Materials and Methods. Standardized Class V cavities were performed in 72 extracted human teeth by means of diamond burs or Er-YAG laser. The samples were randomly divided into six groups of 12, testing three adhesive systems (Clearfil s3 Bond Plus, Xeno® Select, and Futurabond U) for each method used. Cavities were restored with composite resin before thermocycling (methylene blue 2%, 24 h). The slices were prepared using a microtome. Optical microscope photography was employed to measure the penetration. Results. No statistically significant differences in microleakage were found in the use of bur or laser, nor between adhesive systems. Only statistically significant values were observed comparing enamel with cervical walls (). Conclusion. It can be concluded that the Er:YAG laser is as efficient as diamond bur concerning microleakage values in adhesive restoration procedures, thus constituting an alternative tool for tooth preparation. Youssef Sanhadji El Haddar, Sibel Cetik, Babak Bahrami, and Ramin Atash Copyright © 2016 Youssef Sanhadji El Haddar et al. All rights reserved.