BioMed Research International The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight Orthokeratology Wed, 31 Aug 2016 14:32:03 +0000 Purpose. To compare the ocular surface symptoms and signs in an adult population of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of CL wear, overnight orthokeratology (OK). Materials and Methods. This was a prospective and comparative study in which 31 myopic subjects were fitted with the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye questionnaire (DEQ) was filled in at the beginning of the study and then after 15 days, 1 month, and 3 months using each CL modality. The tear quality was evaluated with noninvasive tear break-up time. Tear production was measured with Schirmer test. Tear samples were collected with Schirmer strips being frozen to analyze the dinucleotide diadenosine tetraphosphate (Ap4A) concentration with High-Performance Liquid Chromatography (HPLC). Results. After refitting with ortho-k, a reduction in discomfort and dryness symptoms at the end of the day (, ) was observed. No significant changes were observed in Ap4A concentration in any group. Bulbar redness, limbal redness, and conjunctival staining increased significantly in the Si-Hy group (, Kruskal–Wallis test). Conclusion. Discomfort and dryness symptoms at the end of the day are lower in the OK CL group than in the Si-Hy CL group. Nery García-Porta, Laura Rico-del-Viejo, Alba Martin-Gil, Gonzalo Carracedo, Jesus Pintor, and José Manuel González-Méijome Copyright © 2016 Nery García-Porta et al. All rights reserved. Failure of Polyethylene Inlays in Cementless Total Hip Arthroplasty: A Retrieval Analysis Wed, 31 Aug 2016 12:53:14 +0000 A retrieval analysis has been performed on 50 polyethylene inlays of cementless screw ring implants (Mecring, Mecron, Berlin, Germany) to investigate the failure mechanism of this specific open cup hip arthroplasty design that has shown a high clinical failure rate. Design-specific damage modes like rim creep, collar fatigue, and backside wear were assessed. Furthermore, the inlays were measured using a CMM to determine deformation. In 90% backside wear was observed and collar fatigue occurred in 68% of the cases. Rim creep was present in 38% of the polyethylene inlays. In 90% of the cases the cup opening diameter was 32.1 mm or less and 46% had a diameter less than 32 mm. It seems that creep and deformation of the polyethylene leads to a reduced diameter at the cup opening and consequently decreased clearance. To avoid this type of failure, polyethylene inlays should be supported at the back by the cup to reduce the risk of ongoing creep deformation. Ulrike Mueller, Christoph Lee, Christian Heisel, Marc Thomsen, Rudi G. Bitsch, and J. Philippe Kretzer Copyright © 2016 Ulrike Mueller et al. All rights reserved. Immunopathology of Parasitic Infections and Therapeutic Approaches in Humans and Animals Wed, 31 Aug 2016 11:22:07 +0000 Orlando Paciello, Chiara Palmieri, Iwona Otrocka-Domagala, Laura Rinaldi, Jorge Morales-Montor, and Peter Geldhof Copyright © 2016 Orlando Paciello et al. All rights reserved. Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels Wed, 31 Aug 2016 08:11:48 +0000 Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the “core hub” of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (, ). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (, ). Meanwhile, the correlation between age and grey matter showed no significance (, ). Therefore, age and gray matter/white matter ratio account for different part of -squared (adjusted -squared = 0.5187) as independent variables for predicting GABA levels. Adjusted -squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline. Xuanzi He, Bang-Bon Koo, and Ronald J. Killiany Copyright © 2016 Xuanzi He et al. All rights reserved. Does the Laser-Microtextured Short Implant Collar Design Reduce Marginal Bone Loss in Comparison with a Machined Collar? Wed, 31 Aug 2016 07:53:22 +0000 Purpose. To compare marginal bone loss between subgingivally placed short-collar implants with machined collars and those with machined and laser-microtextured collars. Materials and Methods. The investigators used a retrospective study design and included patients who needed missing posterior teeth replaced with implants. Short-collar implants with identical geometries were divided into two groups: an M group, machined collar; and an L group, machined and laser-microtextured collar. Implants were evaluated according to marginal bone loss, implant success, and probing depth (PD) at 3 years of follow-up. Results. Sixty-two patients received 103 implants (56 in the M group and 47 in the L group). The cumulative survival rate was 100%. All implants showed clinically acceptable marginal bone loss, although bone resorption was lower in the L group (0.49 mm) than in the M group (1.38 mm) at 3 years (). A significantly shallower PD was found for the implants in the L group during follow-up (). Conclusions. Our results suggest predictable outcomes with regard to bone loss for both groups; however, bone resorption was less in the L group than in the M group before and after loading. The laser-microtextured collar implant may provide a shallower PD than the machined collar implant. B. Alper Gultekin, Ali Sirali, Pinar Gultekin, Serdar Yalcin, and Eitan Mijiritsky Copyright © 2016 B. Alper Gultekin et al. All rights reserved. Role of Long Noncoding RNA HOTAIR in the Growth and Apoptosis of Osteosarcoma Cell MG-63 Wed, 31 Aug 2016 06:59:47 +0000 This study investigated the function of HOTAIR in the growth and apoptosis of OS MG-63 cell line in vitro and further clarified its mechanism. The expression levels of HOTAIR in OS MG-63 cell line and normal osteoblast hFOB1.19 cell line were determined by RT-PCR, respectively. The growth and apoptosis of MG-63 cells in vitro were investigated by MTT assay and flow cytometry assay after HOTAIR was knocked down with retroviral vector construction. And the expression levels of cell growth and apoptosis related factors TGF-β, p53, Bcl-2, and TNF-α were determined to clarify the mechanism. We found that HOTAIR was highly expressed in osteosarcoma MG-63 cell line compared with normal osteoblast hFOB1.19 cell line. The proliferation rate was lower and the apoptosis rate was higher significantly in shHOTAIR MG-63 cells than those in EV MG-63 cells. TGF-β and Bcl-2 were downregulated significantly when HOTAIR was knocked down. p53 and TNF-α were upregulated significantly when HOTAIR was knocked down. These results indicated that HOTAIR functioned as a carcinogenic lncRNA, which could promote the proliferation and inhibit the apoptosis of MG-63 cells in vitro. HOTAIR could be a potential target for the treatment of osteosarcoma. Hua Zheng and Jing Min Copyright © 2016 Hua Zheng and Jing Min. All rights reserved. Acute Oral Mammalian Toxicity and Effect of Solvents on Efficacy of Maerua edulis (Gilg. & Ben.) De Wolf against Rhipicephalus (Boophilus) decoloratus Koch, 1844 (Acarina: Ixodidae), Tick Larvae Wed, 31 Aug 2016 06:23:47 +0000 Efficacy and toxicity of aqueous and organic solvents extracts of Maerua edulis against ticks and mice, respectively, were determined. Ground leaves were extracted separately using cold water, cold water plus surfactant (1% v/v liquid soap), hot water plus surfactant, hexane, or methanol to make 25% w/v stock solutions from which serial dilutions of 5, 10, 20, and 25% were made. For each concentration, 20 Rhipicephalus decoloratus tick larvae were put in filter papers impregnated with extracts and incubated for 48 h at 27°C and 85–90% RH for mortality observation after 24 h and 48 h. In the toxicity experiment, hot water plus surfactant treatments of 5, 10, 20, and 25% (w/v) M. edulis were administered in suspension per os to sexually mature Balb/C mice and observed for clinical signs and mortality for 72 h. Larvae mortality was highest (>98%) in methanol-extracted M. edulis treatments (20 and 25%), which was not different from the amitraz-based control (Tickbuster®). Mortality was also higher in the hot water than in cold water plus surfactant treatments (). No postadministration adverse health effects were observed in the mice. These results suggest that M. edulis is an effective tick remedy best extracted using methanol or hot water plus surfactant. Emmanuel T. Nyahangare, Brighton M. Mvumi, and Tatenda Maramba Copyright © 2016 Emmanuel T. Nyahangare et al. All rights reserved. DARE Train-the-Trainer Pedagogy Development Using 2-Round Delphi Methodology Wed, 31 Aug 2016 06:17:35 +0000 The Dispatcher-Assisted first REsponder programme aims to equip the public with skills to perform hands-only cardiopulmonary resuscitation (CPR) and to use an automated external defibrillator (AED). By familiarising them with instructions given by a medical dispatcher during an out-of-hospital cardiac arrest call, they will be prepared and empowered to react in an emergency. We aim to formalise curriculum and standardise the way information is conveyed to the participants. A panel of 20 experts were chosen. Using Delphi methodology, selected issues were classified into open-ended and close-ended questions. Consensus for an item was established at a 70% agreement rate within the panel. Questions that had 60%–69% agreement were edited and sent to the panel for another round of voting. After 2 rounds of voting, 70 consensus statements were agreed upon. These covered the following: focus of CPR; qualities and qualifications of trainers; recognition of agonal breathing; head-tilt-chin lift; landmark for chest compression; performance of CPR when injuries are present; trainers’ involvement in training lay people; modesty of female patients during CPR; AED usage; content of trainer’s manual; addressing of questions and answers; updates-dissemination to trainers and attendance of refresher courses. Recommendations for pedagogy for trainers of dispatcher-assisted CPR programmes were developed. Wei Wei Dayna Yong, Phek Hui Jade Kua, Swee Sung Soon, Pin Pin Maeve Pek, and Marcus Eng Hock Ong Copyright © 2016 Wei Wei Dayna Yong et al. All rights reserved. Prosexual Effect of Chrysactinia mexicana A. Gray (Asteraceae), False Damiana, in a Model of Male Sexual Behavior Tue, 30 Aug 2016 16:33:47 +0000 Chrysactinia mexicana A. Gray (Asteraceae) and Turnera diffusa Willd (Turneraceae) are employed in traditional medicine as aphrodisiacs; however, there is no scientific evidence supporting the prosexual properties of C. mexicana. The aim of this study was to determine whether an aqueous extract of C. mexicana (Cm) stimulates rat male sexual behavior in the sexual exhaustion paradigm. Sexually exhausted (SExh) male rats were treated with Cm (80, 160, and 320 mg/kg), an aqueous extract of T. diffusa (Td), or yohimbine. The sexual exhaustion state in the control group was characterized by a low percentage of males exhibiting mounts, intromissions, and ejaculations and no males demonstrating mating behavior after ejaculation. Cm (320 mg/kg), Td, or yohimbine significantly increased the proportion of SExh rats that ejaculated and resumed copulation after ejaculation. In males that exhibited reversal of sexual exhaustion, Cm (320 mg/kg) improved sexual performance by reducing the number of intromissions and shrinking ejaculation latency. The effects of treatments on sexual behavior were not related with alterations in general locomotion. In conclusion, the prosexual effects of Cm, as well as those of Td, are established at a central level, which supports the traditional use of C. mexicana for stimulating sexual activity. R. Estrada-Reyes, O. A. Ferreyra-Cruz, G. Jiménez-Rubio, O. T. Hernández-Hernández, and L. Martínez-Mota Copyright © 2016 R. Estrada-Reyes et al. All rights reserved. The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD Tue, 30 Aug 2016 15:34:30 +0000 Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor (TGF-) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF- in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF- signaling in the pathogenesis of COPD, which warrants further investigation. Xianyan Liu, Binwei Hao, Ailing Ma, Jinxi He, Xiaoming Liu, and Juan Chen Copyright © 2016 Xianyan Liu et al. All rights reserved. Improved Efficiency and Reliability of NGS Amplicon Sequencing Data Analysis for Genetic Diagnostic Procedures Using AGSA Software Tue, 30 Aug 2016 14:24:13 +0000 Screening for BRCA mutations in women with familial risk of breast or ovarian cancer is an ideal situation for high-throughput sequencing, providing large amounts of low cost data. However, 454, Roche, and Ion Torrent, Thermo Fisher, technologies produce homopolymer-associated indel errors, complicating their use in routine diagnostics. We developed software, named AGSA, which helps to detect false positive mutations in homopolymeric sequences. Seventy-two familial breast cancer cases were analysed in parallel by amplicon 454 pyrosequencing and Sanger dideoxy sequencing for genetic variations of the BRCA genes. All 565 variants detected by dideoxy sequencing were also detected by pyrosequencing. Furthermore, pyrosequencing detected 42 variants that were missed with Sanger technique. Six amplicons contained homopolymer tracts in the coding sequence that were systematically misread by the software supplied by Roche. Read data plotted as histograms by AGSA software aided the analysis considerably and allowed validation of the majority of homopolymers. As an optimisation, additional 250 patients were analysed using microfluidic amplification of regions of interest (Access Array Fluidigm) of the BRCA genes, followed by 454 sequencing and AGSA analysis. AGSA complements a complete line of high-throughput diagnostic sequence analysis, reducing time and costs while increasing reliability, notably for homopolymer tracts. Axel Poulet, Maud Privat, Flora Ponelle, Sandrine Viala, Stephanie Decousus, Axel Perin, Laurence Lafarge, Marie Ollier, Nagi S. El Saghir, Nancy Uhrhammer, Yves-Jean Bignon, and Yannick Bidet Copyright © 2016 Axel Poulet et al. All rights reserved. An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms Tue, 30 Aug 2016 14:17:40 +0000 Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset from Synechococcus elongatus, which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge. Hong-Li Hua, Fa-Zhan Zhang, Abraham Alemayehu Labena, Chuan Dong, Yan-Ting Jin, and Feng-Biao Guo Copyright © 2016 Hong-Li Hua et al. All rights reserved. Osteopontin Promotes Expression of Matrix Metalloproteinase 13 through NF-κB Signaling in Osteoarthritis Tue, 30 Aug 2016 12:38:31 +0000 Osteopontin (OPN) is associated with the severity and progression of osteoarthritis (OA); however, the mechanism of OPN in the pathogenesis of OA is unknown. In this study, we found that OA patients had higher abundance of OPN and matrix metalloproteinase 13 (MMP13). In chondrocytes, we showed that OPN promoted the production of MMP13 and activation of NF-B pathway by increasing the abundance of p65 and phosphorylated p65 and translocation of p65 protein from cytoplasm to nucleus. Notably, inhibition of NF-B pathway by inhibitor suppressed the production of MMP13 induced by OPN treatment. In conclusion, OPN induces production of MMP13 through activation of NF-B pathway. Yusheng Li, Wei Jiang, Hua Wang, Zhenhan Deng, Chao Zeng, Min Tu, Liangjun Li, Wenfeng Xiao, Shuguang Gao, Wei Luo, and Guanghua Lei Copyright © 2016 Yusheng Li et al. All rights reserved. Characterization and Prediction of Protein Flexibility Based on Structural Alphabets Tue, 30 Aug 2016 12:35:34 +0000 Motivation. To assist efforts in determining and exploring the functional properties of proteins, it is desirable to characterize and predict protein flexibilities. Results. In this study, the conformational entropy is used as an indicator of the protein flexibility. We first explore whether the conformational change can capture the protein flexibility. The well-defined decoy structures are converted into one-dimensional series of letters from a structural alphabet. Four different structure alphabets, including the secondary structure in 3-class and 8-class, the PB structure alphabet (16-letter), and the DW structure alphabet (28-letter), are investigated. The conformational entropy is then calculated from the structure alphabet letters. Some of the proteins show high correlation between the conformation entropy and the protein flexibility. We then predict the protein flexibility from basic amino acid sequence. The local structures are predicted by the dual-layer model and the conformational entropy of the predicted class distribution is then calculated. The results show that the conformational entropy is a good indicator of the protein flexibility, but false positives remain a problem. The DW structure alphabet performs the best, which means that more subtle local structures can be captured by large number of structure alphabet letters. Overall this study provides a simple and efficient method for the characterization and prediction of the protein flexibility. Qiwen Dong, Kai Wang, Bin Liu, and Xuan Liu Copyright © 2016 Qiwen Dong et al. All rights reserved. Roles of Rack1 Proteins in Fungal Pathogenesis Tue, 30 Aug 2016 08:00:28 +0000 Pathogenic fungi cause diseases on various organisms. Despite their differences in life cycles, fungal pathogens use well-conserved proteins and pathways to regulate developmental and infection processes. In this review, we focus on Rack1, a multifaceted scaffolding protein involved in various biological processes. Rack1 is well conserved in eukaryotes and plays important roles in fungi, though limited studies have been conducted. To accelerate the study of Rack1 proteins in fungi, we review the functions of Rack1 proteins in model and pathogenic fungi and summarize recent progress on how Rack1 proteins are involved in fungal pathogenesis. Xue Zhang, Rashmi Jain, and Guotian Li Copyright © 2016 Xue Zhang et al. All rights reserved. Extracellular Ribonuclease from Bacillus licheniformis (Balifase), a New Member of the N1/T1 RNase Superfamily Tue, 30 Aug 2016 06:09:26 +0000 The N1/T1 RNase superfamily comprises enzymes with well-established antitumor effects, such as ribotoxins secreted by fungi, primarily by Aspergillus and Penicillium species, and bacterial RNase secreted by B. pumilus (binase) and B. amyloliquefaciens (barnase). RNase is regarded as an alternative to classical chemotherapeutic agents due to its selective cytotoxicity towards tumor cells. New RNase with a high degree of structural similarity with binase (73%) and barnase (74%) was isolated and purified from Bacillus licheniformis (balifase, calculated molecular weight 12421.9 Da, pI 8.91). The protein sample with enzymatic activity of 1.5 × 106 units/A280 was obtained. The physicochemical properties of balifase are similar to those of barnase. However, in terms of its gene organization and promoter activity, balifase is closer to binase. The unique feature of balifase gene organization consists in the fact that genes of RNase and its inhibitor are located in one operon. Similarly to biosynthesis of binase, balifase synthesis is induced under phosphate starvation; however, in contrast to binase, balifase does not form dimers under natural conditions. We propose that the highest stability of balifase among analyzed RNase types allows the protein to retain its structure without oligomerization. Yulia Sokurenko, Alsu Nadyrova, Vera Ulyanova, and Olga Ilinskaya Copyright © 2016 Yulia Sokurenko et al. All rights reserved. Hypothyroidism Affects Olfactory Evoked Potentials Tue, 30 Aug 2016 06:05:06 +0000 Background. Objective electrophysiological methods for investigations of the organ of smell consist in recordings of olfactory cortex responses to specific, time restricted odor stimuli. In hypothyroidism have impaired sense of smell. Material and Methods. Two groups: control of 31 healthy subjects and study group of 21 with hypothyroidism. The inclusion criterion for the study group was the TSH range from 3.54 to 110 μIU/mL. Aim. Assessment of the latency time of evoked responses from the olfactory nerve N1 and the trigeminal nerve N5 using two smells of mint and anise in hypothyroidism. Results. The smell perception in subjective olfactory tests was normal in 85% of the hypothyroid group. Differences were noticed in the objective tests. The detailed intergroup analysis of latency times of recorded cortical responses and performed by means between the groups of patients with overt clinical hypothyroidism versus subclinical hypothyroidism demonstrated a significant difference () whereas no such differences were found between the control group versus subclinical hypothyroidism group (). Conclusion. We can conclude that registration of cortex potentials at irritation of olfactory and trigeminal nerves offers possibilities for using this method as an objective indicator of hypothyroidism severity and prognostic process factor. Teodor Świdziński, Kamila Linkowska-Świdzińska, Hanna Czerniejewska-Wolska, Bożena Wiskirska-Woźnica, Maciej Owecki, Maria Danuta Głowacka, Anna Frankowska, Katarzyna Łącka, Mariusz Glapiński, Zofia Maciejewska-Szaniec, and Piotr Świdziński Copyright © 2016 Teodor Świdziński et al. All rights reserved. Treatment of Pigmented Basal Cell Carcinoma with 3 mm Surgical Margin in Asians Mon, 29 Aug 2016 14:17:31 +0000 Background. In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin. Materials and Methods. 143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (), histology with close proximity group (), and unclear surgical margin group (). Results. Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically. Conclusions. A 3 mm surgical margin is adequate for pigmented BCC. A “wait and see” approach rather than further wide excision is appropriate for BCC with <1 mm free margin. Shang-Hung Lin, Yu-Wen Cheng, Yi-Chien Yang, Ji-Chen Ho, and Chih-Hung Lee Copyright © 2016 Shang-Hung Lin et al. All rights reserved. Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts Mon, 29 Aug 2016 14:12:53 +0000 Near-infrared fluorescence (NIRF) imaging technology is a highly sensitive imaging modality and has been widely used in noninvasively studying the status of receptor expression in small animal models, with an appropriate NIRF probe targeting a specific receptor. In this report, Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5) was evaluated in athymic mice bearing HT-29 tumor xenografts in order to investigate the effect of conjugate on tumor targeting efficacy. In vitro binding studies showed that Mab-Cy5.5 could specifically bind to the cells which expressed CAIX. Results from in vivo imaging showed that HT-29 tumor xenografts can be clearly visualized at 48 h after injection of Mab-Cy5.5, and in the blocking experiment, free anti-CAIX antibody effectively blocked the concentration of Mab-Cy5.5 in the tumors. Western blotting and immunohistochemistry analysis of HT-29 tumor xenografts verified the expression of CAIX in HT-29 tumors. Mab-Cy5.5 could specifically bind to the tumors which expressed CAIX. These results suggested that Mab-Cy5.5 was suitable for CAIX expression imaging in the preclinical research. Jianbo Li, Baoliang Bao, Lei Liu, and Xuemei Wang Copyright © 2016 Jianbo Li et al. All rights reserved. Independent and Combined Effects of Maternal Prepregnancy Body Mass Index and Gestational Weight Gain on Offspring Growth at 0–3 Years of Age Mon, 29 Aug 2016 14:10:27 +0000 Background. The objective of this study was to investigate the independent and combined effects of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) on offspring growth at 0–3 years old. Methods. A total of 826 pairs of nondiabetic mothers and their offspring were recruited in this study. Maternal information was abstracted from medical records and questionnaires. Offspring growth trajectories of weights and BMIs were depicted based on anthropometric measurements. Results. Offspring of mothers who were prepregnancy overweight/obese or obtained excessive GWGs continuously had greater weight and BMI -scores throughout the first 3 years of life. Children of prepregnancy overweight/obese mothers with excessive GWGs had a phenotype of higher weight and BMI -scores than those prepregnancy overweight/obese ones with nonexcessive GWGs from birth to 18 months. Maternal excessive GWGs increased offspring’s risk of overweight/obesity at 12 months (AOR = 1.43, 95% CI: 1.03–2.00) and 24 months (AOR = 1.51, 95% CI: 1.02–2.25). Combination of excessive prepregnancy BMIs and GWGs was significantly associated with offspring’s overweight/obesity at 30 months (AOR = 2.98, 95% CI: 1.36–6.53). Conclusions. Maternal prepregnancy overweight/obesity and excessive GWG are both significantly associated with rapid offspring growth from birth to 3 years old. Excessive GWGs strengthen the effects of high maternal prepregnancy BMIs on excessive offspring growth during their early life. Wen-Yuan Jin, Yao Lv, Yu Bao, Li Tang, Zhi-Wei Zhu, Jie Shao, and Zheng-Yan Zhao Copyright © 2016 Wen-Yuan Jin et al. All rights reserved. Resistance to Second-Line Antituberculosis Drugs and Delay in Drug Susceptibility Testing among Multidrug-Resistant Tuberculosis Patients in Shanghai Mon, 29 Aug 2016 13:09:31 +0000 Introduction. Second-line antituberculosis drugs (SLDs) are used for treating multidrug-resistant tuberculosis (MDR-TB). Prolonged delays before confirming MDR-TB with drug susceptibility testing (DST) could result in transmission of drug-resistant strains and inappropriate use of SLDs, thereby increasing the risk of resistance to SLDs. This study investigated the diagnostic delay in DST and prevalence of baseline SLD resistance in Shanghai and described the distribution of SLD resistance with varied delays to DST. Methods. All registered patients from 2011 to 2013 in Shanghai were enrolled. Susceptibility to ofloxacin, amikacin, kanamycin, and capreomycin was tested. Total delay in DST completion was measured from the onset of symptoms to reporting DST results. Results. Resistance to SLDs was tested in 217 of the 276 MDR-TB strains, with 118 (54.4%) being resistant to at least one of the four SLDs. The median total delay in DST was 136 days. Patients with delay longer than median days were roughly twice more likely to have resistance to at least one SLD (OR 2.22, 95% CI 1.19–4.11). Conclusions. During prolonged delay in DST, primary and acquired resistance to SLDs might occur more frequently. Rapid diagnosis of MDR-TB, improved nosocomial infection controls, and regulated treatment are imperative to prevent SLD resistance. Yong Chen, Zhengan Yuan, Xin Shen, Jie Wu, Zheyuan Wu, and Biao Xu Copyright © 2016 Yong Chen et al. All rights reserved. Association between Toll-Like Receptor 4 Polymorphisms and Systemic Lupus Erythematosus Susceptibility: A Meta-Analysis Mon, 29 Aug 2016 11:53:37 +0000 Family aggregation was observed among systemic lupus erythematosus (SLE) cases, suggesting the genetic factor may contribute to the susceptibility. Toll-like receptors (TLR) play key role in human immune system; in order to gain better insight on the association between TLR4 polymorphisms and SLE risk, a meta-analysis was conducted. In total 4 case-control studies have been included, involving 503 SLE cases and 636 healthy controls. The association between TLR4 polymorphisms and SLE risk was evaluated by calculating pooled odd ratio (OR) and its 95% confidential interval (CI). The -test and statistic were used to estimate the degree of heterogeneity. Publication bias among enrolled studies was examined by using Egger’s test and Begg’s test. Overall, there was no evidence of positive association between SLE risk and D299G and T399I polymorphisms in TLR4. The meta-analysis reported a null association between TLR4 polymorphisms and SLE risk in included study populations, but the role of TLR4 polymorphisms in developing SLE among other populations remains undetermined. Moreover, some laboratory studies still discovered the involvement of TLR4 in SLE process. Therefore, the association between TLR4 polymorphisms and SLE risk requires further investigation both in laboratory and in epidemiological efforts. Weiping Hu, Senchao Wu, Yanlin Zhang, Keshav Raj Sigdel, Yong Lin, and Hongbin Zhong Copyright © 2016 Weiping Hu et al. All rights reserved. Myokines in Response to a Tournament Season among Young Tennis Players Mon, 29 Aug 2016 09:57:22 +0000 The study investigated changes in myokines, heat shock proteins, and growth factors in highly ranked, young, male tennis players in response to physical workload during the competitive season and their potential correlations with match scores. Blood collections were carried out at the beginning, the midpoint, and the end of the tournament season. Data analysis revealed a significant increase in interleukin 6 and its inverse correlation with the number of lost games (; 90% CI −0.06 to 0.77). Neither the irisin nor BDNF level changed notably, yet delta changes of irisin across the season significantly correlated with the number of games won. The concentration of HSP27 recorded a small increase (31.2%; 90% CI 10.7 to 55.5, most likely). A negative correlation was noted between IGF-1 and HSP27 concentration at baseline (−0.70 very high; 90% CI −0.89 to −0.31, very likely). At the end of the season IGF-1 correlated positively with the number of games won ( moderate, 90% CI −0.16 to 0.73, likely) but negatively with the number of games lost (, 90% CI −0.14 to −0.74, likely). In conclusion our data indicated that Il-6, irisin, and growth factor IGF-1 may modify overall performance during a long lasting season, expressed in the amount of games won or lost. K. Witek, P. Żurek, P. Zmijewski, J. Jaworska, P. Lipińska, A. Dzedzej-Gmiat, J. Antosiewicz, and E. Ziemann Copyright © 2016 K. Witek et al. All rights reserved. Preparation and Characterization of Novel Perfluorooctyl Bromide Nanoparticle as Ultrasound Contrast Agent via Layer-by-Layer Self-Assembly for Folate-Receptor-Mediated Tumor Imaging Mon, 29 Aug 2016 09:05:37 +0000 A folate-polyethylene glycol-chitosan derivative was synthesized and its structure was characterized. An optimal perfluorooctyl bromide nanocore template was obtained via utilizing the ultrasonic emulsification method combining with orthogonal design. The targeted nanoparticles containing targeted shell of folate-polyethylene glycol-chitosan derivative and perfluorooctyl bromide nanocore template of ultrasound imaging were prepared successfully by exploiting layer-by-layer self-assembly as contrast agent for ultrasound. Properties of the novel perfluorooctyl bromide nanoparticle were extensively studied by Dynamic Light Scattering and Transmission Electron Microscopy. The targeted nanoparticle diameter, polydispersity, and zeta potential are around 229.5 nm, 0.205, and  mV, respectively. The study revealed that spherical core-shell morphology was preserved. Excellent stability of targeted nanoparticle is evidenced by two weeks of room temperature stability tests. The results of the cell viability assay and the hemolysis test confirmed that the targeted nanoparticle has an excellent biocompatibility for using in cell studies and ultrasound imaging in vivo. Most importantly, in vitro cell experiments demonstrated that an increased amount of targeted nanoparticles was accumulated in hepatocellular carcinoma cell line Bel7402 relative to hepatoma cell line L02. And targeted nanoparticles had also shown better ultrasound imaging abilities in vitro. The data suggest that the novel targeted nanoparticle may be applicable to ultrasonic molecular imaging of folate-receptor overexpressed tumor. Yue Hu, Yong Wang, Jianshuai Jiang, Baosan Han, Shengmin Zhang, Keshi Li, ShuXiong Ge, and Yahui Liu Copyright © 2016 Yue Hu et al. All rights reserved. Functional Assessment of the Foot Undergoing Percutaneous Achilles Tenotomy in Term of Gait Analysis Mon, 29 Aug 2016 09:01:24 +0000 Background. This study was designed to evaluate the function of the foot undergoing the procedure of percutaneous Achilles tenotomy (PAT) in case of clubfoot management in terms of gait analysis. Methods. Nineteen patients with unilateral clubfeet were retrospectively reviewed from our database from July 2012 to June 2016. The result in all the cases was rated as excellent according to the scale of International Clubfoot Study Group (ICSG). The affected sides were taken as Group CF and the contralateral sides as Group CL. Three-dimensional gait analysis was applied for the functional evaluation of the involved foot. Results. Statistical difference was found in physical parameters of passive ankle dorsiflexion and plantar-flexion. No statistical difference was found in temporal-spatial parameters. There was statistical difference in kinematic parameters of total ankle rotation, ankle range of motion, and internal foot progression angle and in kinetic parameters of peak ankle power. No statistical difference was found in other kinematic and kinetic parameters. Conclusions. It is demonstrated that the procedure of PAT is safe and efficient for correcting the equinus deformity in case of clubfoot management and preserving the main function of Achilles tendon at the minimum of four-year follow-up. Yu-Bin Liu, Shu-Yun Jiang, Li Zhao, Yan Yu, Xu-Chen Tao, and Da-Hang Zhao Copyright © 2016 Yu-Bin Liu et al. All rights reserved. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations Mon, 29 Aug 2016 07:12:52 +0000 Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives. Vincenza Granata, Marco Cascella, Roberta Fusco, Nicoletta dell’Aprovitola, Orlando Catalano, Salvatore Filice, Vincenzo Schiavone, Francesco Izzo, Arturo Cuomo, and Antonella Petrillo Copyright © 2016 Vincenza Granata et al. All rights reserved. The Effect of Esmolol on Tissue Perfusion and Clinical Prognosis of Patients with Severe Sepsis: A Prospective Cohort Study Mon, 29 Aug 2016 06:18:26 +0000 Purpose. This study was aimed at investigating the effect of esmolol on tissue perfusion and the clinical prognosis of patients with severe sepsis. Materials and Methods. One hundred fifty-one patients with severe sepsis were selected and divided into the esmolol group () or the control group (), who received conventional antiseptic shock treatment. The esmolol group received a continuous infusion of esmolol via a central venous catheter, and their heart rate (HR) was maintained at 70–100 bpm over 72 hours. Results. The HR of all patients reached the target level within 72 hours of treatment for both groups. The effect of esmolol on PvaCO2 was only significant at 48 hours (). ScvO2 increased in the esmolol group and decreased in the control group (). Lac showed a linear downward trend over the treatment time, but the reduction was more significant in the control group at 48 hours () between the two groups. Kaplan-Meier analysis showed a significantly shorter duration of mechanical ventilation in the esmolol group than in the control group (). Conclusions. Esmolol reduced the duration of mechanical ventilation in patients with severe sepsis, with no significant effect on circulatory function or tissue perfusion. Xiuling Shang, Kaiyu Wang, Jingqing Xu, Shurong Gong, Yong Ye, Kaihua Chen, Fayang Lian, Wei Chen, and Rongguo Yu Copyright © 2016 Xiuling Shang et al. All rights reserved. Molecular Imaging for Personalized Medicine Mon, 29 Aug 2016 06:16:50 +0000 James Russell, Jie Tian, Seigo Kinuya, Baozhong Shen, and Xiao-Feng Li Copyright © 2016 James Russell et al. All rights reserved. Biosynthesis and Characterization of Silver Nanoparticles by Aspergillus Species Mon, 29 Aug 2016 06:08:30 +0000 Currently, researchers turn to natural processes such as using biological microorganisms in order to develop reliable and ecofriendly methods for the synthesis of metallic nanoparticles. In this study, we have investigated extracellular biosynthesis of silver nanoparticles using four Aspergillus species including A. fumigatus, A. clavatus, A. niger, and A. flavus. We have also analyzed nitrate reductase activity in the studied species in order to determine the probable role of this enzyme in the biosynthesis of silver nanoparticles. The formation of silver nanoparticles in the cell filtrates was confirmed by the passage of laser light, change in the color of cell filtrates, absorption peak at 430 nm in UV-Vis spectra, and atomic force microscopy (AFM). There was a logical relationship between the efficiencies of studied Aspergillus species in the production of silver nanoparticles and their nitrate reductase activity. A. fumigatus as the most efficient species showed the highest nitrate reductase activity among the studied species while A. flavus exhibited the lowest capacity in the biosynthesis of silver nanoparticles which was in accord with its low nitrate reductase activity. The present study showed that Aspergillus species had potential for the biosynthesis of silver nanoparticles depending on their nitrate reductase activity. Kamiar Zomorodian, Seyedmohammad Pourshahid, Arman Sadatsharifi, Pouyan Mehryar, Keyvan Pakshir, Mohammad Javad Rahimi, and Ali Arabi Monfared Copyright © 2016 Kamiar Zomorodian et al. All rights reserved. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects Mon, 29 Aug 2016 06:04:18 +0000 A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration. Shu He, Kai-Feng Lin, Jun-Jun Fan, Gang Hu, Xin Dong, Yi-Nan Zhao, Yue Song, Zhong-Shang Guo, Long Bi, and Jian Liu Copyright © 2016 Shu He et al. All rights reserved.