bluuebunny/crossref_metadata_2025 huggingface dataset:
HOXB9 Expression Correlates with Histological Grade and Prognosis in LSCC
Authors: Sun Chuanhui , Han Changsong , Wang Peng , Jin Yinji , Sun Yanan , Qu Lingmei
Published: July 2017

The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P<0.001). HOXB9 was found to correlate with histological grade (P<0.01) and prognosis (P<0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients.
Training Online Physical Educators: A Phenomenological Case Study
Authors: Goad Tyler , Jones Emily
Published: July 2017

Online physical education (OLPE) presents a unique set of challenges in translating traditional physical education to a digital space, all while meeting the same benchmarks, curriculum, and assessment standards of traditional courses. Currently, limited research exists investigating how physical educators are formally trained to deliver content online. Therefore, the purpose of this study was to describe the experiences and perceptions of students and instructor of a graduate‐level OLPE teacher education (OLPETE) methods course. A phenomenographic research design was employed to examine the social phenomenon of one OLPETE methods course at a midwest midmajor college. Participants in this study were an instructor of OLPETE methods course and former students who had completed the course. Data for the case study were collected through semistructured interviews and inductive content analysis was employed to analyze the qualitative data. Results revealed four categories describing the lived experiences of those involved: (1) Modeling Online Instructional Practices, (2) Instructor and Student Interactions, (3) Transitioning Pedagogical and Content Knowledge Online, and (4) Navigating Instructional Tools and Technology.
Quality of Vision after Deep Anterior Lamellar Keratoplasty (Fluid Dissection) Compared to Penetrating Keratoplasty for the Treatment of Keratoconus
Authors: Hamdi Islam Mahmoud , Hamdi Momen Mahmoud
Published: July 2017

Purpose. To compare the visual quality of patients with keratoconus who underwent penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK) with fluid dissection. Design. Cross-sectional, observational study. Methods. Twelve eyes that underwent PKP (PKP group) were compared to 24 eyes that underwent DALK (DALK group) after complete removal of sutures and stability of refraction. Visual, refractive, corneal topographic, corneal aberrometry, and ocular aberrometry parameters were compared for both groups. The χ2 and Mann–Whitney U tests were used for comparisons as appropriate. P<0.05 was considered statistically significant. Results. Uncorrected and best spectacle-corrected visual acuity (UCVA and BSCVA, resp.), mean refractive spherical equivalent and mean refractive cylinder (MRSE and MRC, resp.), root mean square of the 3 mm and 5 mm OPD Scan (NIDEK Co. Ltd., Gamagori, Japan), steep and flat meridians (SimK1 and SimK2, resp.), and the difference (corneal cylinder) were not statistically significantly different between groups (P>0.05, all comparisons). All aberrations, point spread functions (PSF), and the modulation transfer function (MTF) were not statistically different between groups (P>0.05). Conclusion. For our small study, the postoperative PKP and DALK with fluid dissection patient groups had vision/optical quality parameters that were not statistically different. This may indicate that DALK with fluid dissection can replace PKP for keratoconus without compromising vision quality.
Research on Mud Flow Rate Measurement Method Based on Continuous Doppler Ultrasonic Wave
Authors: Zhou Quan , Zhao Hui , He Yufa , Li Shengnan , Jiang Shiquan , Zhang Huijie
Published: July 2017

In deep-water drilling processes, the flow rate of drilling mud inside an annular pipe is significant judgment data for early kick detection. On the basis of the continuous-wave Doppler ultrasound, this paper proposes a new detection method of nonoriented continuous-wave Doppler ultrasound. The method solves the problem of the ultrasound having great attenuation in mud and not receiving effective signals by using a continuous ultrasound. Moreover, this method analyzes the nonoriented characteristics of ultrasound reflection on principle and proposes the detection of ultrasound Doppler frequency shift by detecting Lamb wave, which releases the detection of oil-based mud flow rate in a nonintrusive annular pipe. The feasibility of the method is verified through theoretical analysis and numerous experiments on a gas kick simulation platform. The measurement result has reached a flow accuracy approximating to the intrusive flow meter.
Time-Domain Analytical Expression for Near Fields of Arbitrarily Oriented Electric Dipole and Its Application
Authors: Yang Qian , Wei Bing , He Xinbo , Gong Minghao
Published: July 2017

The near fields of electric dipole are commonly used in wide-band analysis of complex electromagnetic problems. In this paper, we propose new near field time-domain expressions for electric dipole. The analytical expressions for the frequency-domain of arbitrarily oriented electric dipole are given at first; next we give the time-domain expressions by time-frequency transformation. The proposed expressions are used in hybrid TDIE/DGTD method for analysis of circular antenna with radome. The accuracy of the proposed algorithm is verified by numerical examples.
Large-Scale Analysis of Relationships between Mineral Dust, Ice Cloud Properties, and Precipitation from Satellite Observations Using a Bayesian Approach: Theoretical Basis and First Results for the Tropical Atlantic Ocean
Authors: Klüser Lars , Popp Thomas
Published: July 2017

Mineral dust and ice cloud observations from the Infrared Atmospheric Sounding Interferometer (IASI) are used to assess the relationships between desert dust aerosols and ice clouds over the tropical Atlantic Ocean during the hurricane season 2008. Cloud property histograms are first adjusted for varying cloud top temperature or ice water path distributions with a Bayesian approach to account for meteorological constraints on the cloud variables. Then, histogram differences between dust load classes are used to describe the impact of dust load on cloud property statistics. The analysis of the histogram differences shows that ice crystal sizes are reduced with increasing aerosol load and ice cloud optical depth and ice water path are increased. The distributions of all three variables broaden and get less skewed in dusty environments. For ice crystal size the significant bimodality is reduced and the order of peaks is reversed. Moreover, it is shown that not only are distributions of ice cloud variables simply shifted linearly but also variance, skewness, and complexity of the cloud variable distributions are significantly affected. This implies that the whole cloud variable distributions have to be considered for indirect aerosol effects in any application for climate modelling.
Flexural and Shear Behaviors of Reinforced Alkali-Activated Slag Concrete Beams
Authors: Lee Kwang-Myong , Choi Sung , Choo Jinkyo F. , Choi Young-Cheol , Yoo Sung-Won
Published: July 2017

The material properties of cement-zero concrete using alkali-activators have been studied extensively as the latest response to reduce the CO2 exhaust of the cement industry. However, it is also critical to evaluate the behavior of reinforced concrete beams made of alkali-activated slag (AAS) concrete in terms of flexure and shear to promote the applicability of AAS concrete as structural material. Accordingly, nine types of beam specimens with various ratios of tensile steel and stirrup were fabricated and subject to bending and shear tests. The results show that the flexural and shear behaviors of the reinforced AAS concrete members are practically similar to those made of normal concrete and indicate the applicability of the conventional design code given that the lower density of slag is considered. In addition, a framework using the elastic modulus and stress-strain relation from earlier research is adopted to carry out nonlinear finite element analysis reflecting the material properties of AAS concrete. The numerical results exhibit good agreement with the experimental results and demonstrate the validity of the analytical model.
A Circularly Polarized HTS Microstrip Antenna Array with Controllable Cryostat
Authors: Zeng Xiaoyong , Huang Kama , Hu Zhongxia , Chen Qian , Xiao Wei
Published: July 2017

A high-temperature superconductor (HTS) microstrip antenna array with right-hand circular polarization is proposed for space communications. The proposed HTS antenna array can achieve high efficiency, which is able to reduce the antenna’s loss. The array consists of 16 antenna elements being fed by a T-network. A pair of symmetric meander slots is used in each antenna element to broaden the input matching bandwidth. A controllable cryostat is used as the refrigeration for HTS. The experiment shows that the gain of the proposed HTS antenna is 8.39 dB, whose 10 dB return loss bandwidth is 2.2% ranging from 5.75 GHz to 5.87 GHz. In comparison with a traditional conductor antenna array having the same configuration, the proposed array has an 8.1 dB improvement in the gain and a 69.2% enhancement in the radiation efficiency.
HLA Class II Allele, Haplotype, and Genotype Associations with Type 1 Diabetes in Benin: A Pilot Study
Authors: Fagbemi Kaossarath A. , Medehouenou Thierry C. Marc , Azonbakin Simon , Adjagba Marius , Osseni Razack , Ahoueya Jocelyne , Agbanlinsou Arnaud , Darboux Raphael , Baba-Moussa Lamine , Laleye Anatole
Published: July 2017

Background. Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D). Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D.Material and Methods. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes.Results. Participants were aged 1–24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02.Conclusion. Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.
Mesenchymal Stem Cells Promote Metastasis of Lung Cancer Cells by Downregulating Systemic Antitumor Immune Response
Authors: Gazdic Marina , Simovic Markovic Bojana , Jovicic Nemanja , Misirkic-Marjanovic Maja , Djonov Valentin , Jakovljevic Vladimir , Arsenijevic Nebojsa , Lukic Miodrag L. , Volarevic Vladislav
Published: July 2017

Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice. MSCs profoundly reduced infiltration of macrophages, TNF-α-producing dendritic cells (DCs), TNF-α-, and IL-17-producing CD4+ T cells but increased IL-10-producing CD4+ T lymphocytes in the lungs of tumor-bearing animals. The total number of lung-infiltrated, cytotoxic FasL, perforin-expressing, TNF-α-, and IL-17-producing CD8+ T lymphocytes, and NKG2D-expressing natural killer (NK) cells was significantly reduced in LLC1 + MSC-treated mice. Cytotoxicity of NK cells was suppressed by MSC-conditioned medium. This phenomenon was abrogated by the inhibitors of inducible nitric oxide synthase (iNOS) and indoleamine 2,3-dioxygenase (IDO), suggesting the importance of iNOS and IDO for MSC-mediated suppression of antitumor cytotoxicity of NK cells. This study provides the evidence that MSCs promote lung cancer metastasis by suppressing antitumor immune response raising concerns regarding safety of MSC-based therapy in patients who have genetic susceptibility for malignant diseases.
A Flexible Load Control Strategy for Distribution Network to Reduce the Line Losses and to Eliminate the Transmission Congestion
Authors: Wang Beibei , Hu Xiaoqing , Shen Peifeng , Ji Wenlu , Cao Yang , Tang Jiaping
Published: July 2017

There are many uncertain factors in the modern distribution network, including the access of renewable energy sources and the heavy load level. The existence of these factors has brought challenges to the stability of the power distribution network, as well as increasing the risk of exceeding transmission capacity of distribution lines. The appearance of flexible load control technology provides a new idea to solve the above problems. Air conditioners (ACs) account for a great proportion of all loads. In this paper, the model of dispatching AC loads in the regional power grid is constructed, and the direct load control (DLC) method is adopted to reduce the load of ACs. An improved tabu search technique is proposed to solve the problem of network dispatch in distribution systems in order to reduce the resistive line losses and to eliminate the transmission congestion in lines under normal operating conditions. The optimal node solution is obtained to find the best location and reduction capacity of ACs for load control. To demonstrate the validity and effectiveness of the proposed method, a test system is studied. The numerical results are also given in this article, which reveal that the proposed method is promising.
Yacon (Smallanthus sonchifolius) Leaf Extract Attenuates Hyperglycemia and Skeletal Muscle Oxidative Stress and Inflammation in Diabetic Rats
Authors: Santos Klinsmann Carolo dos , Bueno Bianca Guerra , Pereira Luana Ferreira , Francisqueti Fabiane Valentini , Braz Mariana Gobbo , Bincoleto Lahis Fernandes , Silva Lilian Xavier da , Ferreira Ana Lúcia A. , Nakamune Ana Cláudia de Melo Stevanato , Chen C.-Y. Oliver , Blumberg Jeffrey B. , Corrêa Camila Renata
Published: July 2017

The effects of hydroethanolic extract of Yacon leaves (HEYL) on antioxidant, glycemic, and inflammatory biomarkers were tested in diabetic rats. Outcome parameters included glucose, insulin, interleukin‐6 (IL‐6), and hydrophilic antioxidant capacity (HAC) in serum and IL‐6, HAC, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in soleus. The rats (10/group) were divided as follows: C, controls; C + Y, HEYL treated; DM, diabetic controls; and DM + Y, diabetic rats treated with HEYL. Diabetes mellitus was induced by administration of streptozotocin. C + Y and DM + Y groups received 100 mg/kg HEYL daily via gavage for 30 d. Hyperglycemia was improved in the DM + Y versus DM group. Insulin was reduced in DM versus C group. DM rats had higher IL‐6 and MDA and lower HAC in the soleus muscle. HEYL treatment decreased IL‐6 and MDA and increased HAC in DM rats. DM + Y rats had the highest CAT activity versus the other groups; GPx was higher in C + Y and DM + Y versus their respective controls. The apparent benefit of HEYL may be mediated via improving glucoregulation and ameliorating oxidative stress and inflammation, particularly in diabetic rats.
Differential MicroRNA Analyses of Burkholderia pseudomallei- and Francisella tularensis-Exposed hPBMCs Reveal Potential Biomarkers
Authors: Cer Regina Z. , Herrera-Galeano J. Enrique , Frey Kenneth G. , Schully Kevin L. , Luu Truong V. , Pesce John , Mokashi Vishwesh P. , Keane-Myers Andrea M. , Bishop-Lilly Kimberly A.
Published: July 2017

Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5α. RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis-exposed hPBMCs.
A Unique Case for Spinal Cord Stimulation: Successful Treatment of Small Fiber Neuropathy Pain Using Multiple Spinal Cord Stimulators
Authors: Eckmann Maxim , Papanastassiou Alexander , Awad Mark
Published: July 2017

Spinal cord stimulators have commonly been used to treat multiple pain conditions. This case report represents a unique case of using multiple spinal cord stimulators for widespread small fiber neuropathy pain. This case report concerns patient JJ who first presented with generalized neuropathic pain. His pain was an intermittent burning, stinging quality that originally focused in both of his feet and progressed to include his legs and arms and eventually involved his entire body. The pain would last moments to hours at least daily. He reported a poor quality of life. He was diagnosed with small fiber neuropathy with anhydrosis, suggestive of idiopathic erythromelalgia. He had a spinal cord stimulator trial involving both cervical and lower thoracic percutaneous leads. After two spinal cord stimulators were implanted, the patient began to report an improvement in pain. The patient continues to report excellent pain relief. The patient uses the stimulator intermittently as needed, in an abortive fashion for pain flares. The patient is very pleased and has increased his activity. He now attends graduate school full time. This case report hopes to illustrate a unique use of multiple spinal cord stimulators in treating widespread neuropathic pain caused by small fiber neuropathy.
Bark Extracts of Ceylon Cinnamon Possess Antilipidemic Activities and Bind Bile Acids In Vitro
Authors: Abeysekera Walimuni Prabhashini Kaushalya Mendis , Arachchige Sirimal Premakumara Galbada , Ratnasooriya Wanigasekera Daya
Published: July 2017

Ethanol (95%) and dichloromethane : methanol (1 : 1) bark extracts of authenticated Ceylon cinnamon were investigated for range of antilipidemic activities (ALA): HMG‐CoA reductase, lipase, cholesterol esterase, and cholesterol micellization inhibitory activities and bile acids binding in vitro. Individual compounds in bark extracts were also evaluated. Bark extracts showed ALA in all the assays studied. The IC50 (μg/mL) values ranged within 153.07 ± 8.38–277.13 ± 32.18, 297.57 ± 11.78–301.09 ± 4.05, 30.61 ± 0.79–34.05 ± 0.41, and 231.96 ± 9.22–478.89 ± 9.27, respectively, for HMG‐CoA reductase, lipase, cholesterol esterase, and cholesterol micellization inhibitory activities. The bile acids binding (3 mg/mL) for taurocholate, glycodeoxycholate, and chenodeoxycholate ranged within 19.74 ± 0.31–20.22 ± 0.31, 21.97 ± 2.21–26.97 ± 1.61, and 16.11 ± 1.42–19.11 ± 1.52%, respectively. The observed ALA were moderate compared to the reference drugs studied. Individual compounds in bark extracts ranged within 2.14 ± 0.28–101.91 ± 3.61 and 0.42 ± 0.03–49.12 ± 1.89 mg/g of extract. Cinnamaldehyde and gallic acid were the highest and the lowest among the tested compounds. The ethanol extract had highest quantity of individual compounds and ALA investigated. Properties observed indicate usefulness of Ceylon cinnamon bark in managing hyperlipidemia and obesity worldwide. Further, this study provides scientific evidence for the traditional claim that Ceylon cinnamon has antilipidemic activities.
CC_TRS: Continuous Clustering of Trajectory Stream Data Based on Micro Cluster Life
Authors: Riyadh Musaab , Mustapha Norwati , Sulaiman Md. Nasir , Sharef Nurfadhlina Binti Mohd
Published: July 2017

The rapid spreading of positioning devices leads to the generation of massive spatiotemporal trajectories data. In some scenarios, spatiotemporal data are received in stream manner. Clustering of stream data is beneficial for different applications such as traffic management and weather forecasting. In this article, an algorithm for Continuous Clustering of Trajectory Stream Data Based on Micro Cluster Life is proposed. The algorithm consists of two phases. There is the online phase where temporal micro clusters are used to store summarized spatiotemporal information for each group of similar segments. The clustering task in online phase is based on temporal micro cluster lifetime instead of time window technique which divides stream data into time bins and clusters each bin separately. For offline phase, a density based clustering approach is used to generate macro clusters depending on temporal micro clusters. The evaluation of the proposed algorithm on real data sets shows the efficiency and the effectiveness of the proposed algorithm and proved it is efficient alternative to time window technique.
Integrated SINS/WSN Positioning System for Indoor Mobile Target Using Novel Asynchronous Data Fusion Method
Authors: Yang Hai , Li Wei , Luo Chengming , Zhang Jinyao , Si Zhuoyin
Published: July 2017

According to the asynchronous transmission of data for the SINS/WSN integrated positioning system, this paper proposes a novel asynchronous data fusion method using Unscented Kalman Filter for SINS/WSN integrated positioning system based on indoor mobile target. The state equation of the integrated system is built with the motion characteristic of mobile target. The pseudo measurement equation is built based on the time sequence of SINS/WSN measured value through detecting the measurement of WSN in every fusion period. Considering that the improved state-space model, comprised of the state equation and pseudo measurement equation, is the nonlinear equations, the Unscented Kalman Filter is applied to estimate the state value of the state-space model. Hence the asynchronous data fusion method for SINS/WSN integrated positioning system can be achieved. Simulation results and experimental tests show that the positioning system with proposed asynchronous data fusion algorithm performs feasibility and stability under circumstances of the asynchronous time, and it is superior to the traditional asynchronous data fusion and synchronous data fusion methods.
Firefly Mating Algorithm for Continuous Optimization Problems
Authors: Ritthipakdee Amarita , Thammano Arit , Premasathian Nol , Jitkongchuen Duangjai
Published: July 2017

This paper proposes a swarm intelligence algorithm, called firefly mating algorithm (FMA), for solving continuous optimization problems. FMA uses genetic algorithm as the core of the algorithm. The main feature of the algorithm is a novel mating pair selection method which is inspired by the following 2 mating behaviors of fireflies in nature: (i) the mutual attraction between males and females causes them to mate and (ii) fireflies of both sexes are of the multiple-mating type, mating with multiple opposite sex partners. A female continues mating until her spermatheca becomes full, and, in the same vein, a male can provide sperms for several females until his sperm reservoir is depleted. This new feature enhances the global convergence capability of the algorithm. The performance of FMA was tested with 20 benchmark functions (sixteen 30-dimensional functions and four 2-dimensional ones) against FA, ALC-PSO, COA, MCPSO, LWGSODE, MPSODDS, DFOA, SHPSOS, LSA, MPDPGA, DE, and GABC algorithms. The experimental results showed that the success rates of our proposed algorithm with these functions were higher than those of other algorithms and the proposed algorithm also required fewer numbers of iterations to reach the global optima.
Association of SUDOSCAN Values with Vibration Perception Threshold in Chinese Patients with Type 2 Diabetes Mellitus
Authors: Zhu Xiaoming , Mao Fei , Liu Siying , Zheng Hangping , Lu Bin , Li Yiming
Published: July 2017

Aims/Introduction. SUDOSCAN has been proved to be an efficient method in detecting diabetic microvascular complications. In this study, we determine to detect the possible relationship between vibration perception threshold (VPT) and cardiac autonomic neuropathy (CAN) values produced by SUDOSCAN. Materials and Methods. A total of 920 Chinese patients with T2DM were enrolled in the study. Spearman correlation analysis and multivariate regression analysis were performed to determine the relation between CAN and VPT values. Mean VPT values across the CAN value tertiles were analyzed stratified by HbA1c status. Results. In the study, we discovered a relatively high correlation between CAN value and both VPT values from dorsal feet and toes. Multivariate regression analyses also showed a significant relation between VPT and CAN values after adjusting all covariates. The mean value of VPT decreased across the SUDOSCAN-CAN value quartiles in both groups, and it was higher in patients with HbA1C > 9% than in patients with HbA1C < 9% across all quartiles of the SUDOSCAN-CAN except for the VPT mean in the low quartile of the SUDOSCAN-CAN value. Conclusions. All these results suggested that SUDOSCAN-CAN result was associated with VPT value which indicated a probable link between VPT value and cardiovascular autonomic dysfunction.
ROS‐Mediated Apoptosis and Genotoxicity Induced by Palladium Nanoparticles in Human Skin Malignant Melanoma Cells
Authors: Alarifi Saud , Ali Daoud , Alkahtani Saad , Almeer Rafa S.
Published: July 2017

The present work was designed to investigate the effect of palladium nanoparticles (PdNPs) on human skin malignant melanoma (A375) cells, for example, induction of apoptosis, cytotoxicity, and DNA damage. Diseases resulting from dermal exposure may have a significant impact on human health. There is a little study that has been reported on the toxic potential of PdNPs on A375. Cytotoxic potential of PdNPs (0, 5, 10, 20, and 40 μg/ml) was measured by tetrazolium bromide (MTT assay) and NRU assay in A375 cells. PdNPs elicited concentration and time‐dependent cytotoxicity, and longer exposure period induced more cytotoxicity as measured by MTT and NRU assay. The molecular mechanisms of cytotoxicity through cell cycle arrest and apoptosis were investigated by AO (acridine orange)/EtBr (ethidium bromide) stain and flow cytometry. PdNPs not only inhibit proliferation of A375 cells in a dose‐ and time‐dependent model but also induce apoptosis and cell cycle arrest at G2/M phase (before 12 h) and S phase (after 24 h). The induction of oxidative stress in A375 cells treated with above concentration PdNPs for 24 and 48 h increased ROS level; on the other hand, glutathione level was declined. Apoptosis and DNA damage was significantly increased after treatment of PdNPs. Considering all results, PdNPs showed cytotoxicity and genotoxic effect in A375 cells.
Simultaneous Determination of 11 Compounds in Gualou Guizhi Granule and Pharmacokinetics Study by UPLC-MS/MS
Authors: Sun Chengtao , Xu Wen , Zhang Yuqin , Yu Lishuang , Ye Miao , Chu Kedan , Xu Wei , Lin Yu
Published: July 2017

A rapid and sensitive ultrafast performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) was developed for the simultaneous determination of 11 compounds in Gualou Guizhi Granule (GLGZG), including liquiritin, isoliquiritin, liquirtin apioside, isoliquiritin apioside, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, paeoniflorin, albiflorin, and paeoniflorin sulfonate in rat plasma. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 × 100 mm, 1.6 μm) with the mobile phase consisting of 0.1% aqueous formic acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.25 mL·min−1. The method was linear for all analytes within the detection range (r≥0.9597). The inter- and intraday precision (RSD) were 2.21–6.41% and 1.67–6.18%; the inter- and intraday accuracy (recover) were 92.48–114.03% and 90.23–112.04%. And the recovery rate ranged from 81.30% to 108.22%. The matrix effect values obtained for analytes ranged from 88.91% to 113.32%. This validated method was successfully applied to a pharmacokinetics study in rats after oral administration of GLGZG.
Epigenetics and Oxidative Stress in Aging
Authors: Guillaumet-Adkins Amy , Yañez Yania , Peris-Diaz Manuel D. , Calabria Ines , Palanca-Ballester Cora , Sandoval Juan
Published: July 2017

Aging is a multifactorial process characterized by the progressive loss of physiological functions, leading to an increased vulnerability to age‐associated diseases and finally to death. Several theories have been proposed to explain the nature of aging. One of the most known identifies the free radicals produced by the mitochondrial metabolism as the cause of cellular and DNA damage. However, there are also several evidences supporting that epigenetic modifications, such as DNA methylation, noncoding RNAs, and histone modifications, play a critical role in the molecular mechanism of aging. In this review, we explore the significance of these findings and argue how the interlinked effects of oxidative stress and epigenetics can explain the cause of age‐related declines.
Predictors for Mortality among Multidrug-Resistant Tuberculosis Patients in Tanzania
Authors: Mollel Edson W. , Chilongola Jaffu O.
Published: July 2017

Problem. Factors related to MDRTB mortality in Tanzania have not been adequately explored and reported.Objectives. To determine demographic, clinical, radiographic, and laboratory factors associated with MDRTB mortality in a Tanzanian TB Referral Hospital.Methodology. This was a cross-sectional study with 193 participants. Demographic, clinical, laboratory, and radiological data were collected, and their associations with mortality among MDRTB patients were determined.Results and Conclusions. Cough was the commonest finding among these MDRTB patients, with 179 (92.75%) of them presenting with cough, followed by chest X-ray consolidation in 156 patients (80.83%) and history of previous TB treatment in 151 patients (78.24%). Cigarette smoking, HIV positivity, and low CD4 counts were significantly associated with MDRTB mortality,pvalues of 0.034, 0.044, and 0.048, respectively. Fever on the other hand was at the borderline withpvalue of 0.059. We conclude that cigarette smoking and HIV status are significant risk factors for mortality among MDRTB patients. HIV screening should continually be emphasized among patients and the general community for early ARTs initiation. Based on the results from our study, policy makers and public health personnel should consider addressing tobacco cessation as part of national TB control strategy.
Visual Evoked Potentials in Primary Open Angle Glaucoma
Authors: Jha Mukesh Kumar , Thakur Dilip , Limbu Nirmala , Badhu Badri Prasad , Paudel Bishnu Hari
Published: July 2017

Background and Aims. Visual evoked potentials (VEPs) assess the integrity of the visual pathways from the optic nerve to the occipital cortex. Optic disc cupping and visual field loss have been associated with prolongation of latency of VEP in primary open angle glaucoma (POAG). Methods. Pattern reversal and flash VEP tests were done in consenting 20 primary open angle glaucoma eyes and 40 normal control eyes. Results. In POAG cases, the refractive error [3.51±1.88 versus 1.88±1.11, D, p=0.001], cup-disc ratio in percent [66.00±16.98 versus 28.50±5.80, p=0.001], intraocular pressure [19.55±2.08 versus 11.65±1.64, mmHg, p=0.001], and automated visual field pattern standard deviation [4.13±6.96 versus 1.64±0.45, dB, p=0.001] were significantly more than in control. The visual acuity [0.41±0.29 versus 1.00±0.00, p=0.001], foveal visual sensitivity [25.92±6.88 versus 33.48±1.75, dB, p=0.001], and automated visual field mean deviation [−9.63±10.58 versus 0.07±1.54, dB, p=0.001] were significantly less in cases than in control. Among VEP variables, pattern reversal latency N145 [149.00±15.75 versus 137.52±15.20, ms, p=0.011], flash amplitude N75 [2.18±.57 versus 1.47±.38, μV, p=0.001], and flash amplitude N145 [1.99±.39 versus 1.43±.38, μV, p=0.001] were increased in cases. The pattern reversal amplitude N75 [1.97±.35 versus 2.47±.58, μV, p=0.001], amplitude P100 [3.09±.46 versus 6.07±1.44, μV, p=0.001], and amplitude N145 [2.21±.58 versus 4.45±1.99, μV, p=0.001] were decreased in cases. Conclusions. POAG caused glaucomatous damage to optic pathway.
Assessment of Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance T1 Mapping: Correlation with Left-Ventricular Diastolic Dysfunction and Diabetic Duration
Authors: Shang Yongning , Zhang Xiaochun , Leng Weilling , Chen Liu , Lei Xiaotian , Zhang Tianjing , Greiser Andreas , Liang Ziwen , Wang Jian
Published: July 2017

Purpose. To quantify extracellular matrix expansion with the cardiovascular magnetic resonance (CMR) T1 mapping technique and the derived extracellular volume fraction (ECV) in diabetic cardiomyopathy (DbCM) patients and to detect the relationship among ECV, duration of diabetes, and diastolic function. Materials. Thirty-eight patients with diabetic cardiomyopathy (20 males, age 54.6 ± 8.6 years) and thirty-two matched normal controls (15 males, age 51.4 ± 13.6 years) were prospectively enrolled. All of them were scanned by T1 mapping to obtain the native and postcontrast T1 values of myocardium and blood, and ECV was calculated accordingly. All patients also underwent transthoracic echocardiographic tissue Doppler imaging to assess left-ventricular diastolic function. Results. There was a significant difference in ECV between the two groups (DbCMs 30.4 ± 2.9% versus controls 27.1 ± 2.4%, P<0.001). The duration of diabetes was positively and strongly associated with ECV (R=0.539, P=0.0005). There was also a significant difference in ECV (P≤0.001) among four groups (A, controls; B, DbCM patients with duration of diabetes <5 years; C, 5–10 years; and D, >10 years). ECV was negatively associated with LV E’/A’ (R=−0.403, P=0.012). Conclusion. CMR T1 mapping can reflect myocardial extracellular matrix expansion in DbCM and can be a powerful technique for the early diagnosis of DbCM.
Extracellular DNA Contributes to Dental Biofilm Stability
Authors: Schlafer Sebastian , Meyer Rikke L. , Dige Irene , Regina Viduthalai R.
Published: July 2017

Extracellular DNA (eDNA) is a major matrix component of many bacterial biofilms. While the presence of eDNA and its role in biofilm stability have been demonstrated for several laboratory biofilms of oral bacteria, there is no data available on the presence and function of eDNA in in vivo grown dental biofilms. This study aimed to determine whether eDNA was part of the matrix in biofilms grown in situ in the absence of sucrose and whether treatment with DNase dispersed biofilms grown for 2.5, 5, 7.5, 16.5, or 24 h. Three hundred biofilms from 10 study participants were collected and treated with either DNase or heat-inactivated DNase for 1 h. The bacterial biovolume was determined with digital image analysis. Staining with TOTO®-1 allowed visualization of eDNA both on bacterial cell surfaces and, with a cloud-like appearance, in the intercellular space. DNase treatment strongly reduced the amount of biofilm in very early stages of growth (up to 7.5 h), but the treatment effect decreased with increasing biofilm age. This study proves the involvement of eDNA in dental biofilm formation and its importance for biofilm stability in the earliest stages. Further research is required to uncover the interplay of eDNA and other matrix components and to explore the therapeutic potential of DNase treatment for biofilm control.
Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study
Authors: Tal Kfir , Dotan Assaf , Nisgav Yael , Dachbash Mor , Gal-Or Orly , Ehrlich Rita , Gaton Dan D. , Weinberger Dov , Livnat Tami
Published: July 2017

Purpose: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. Methods: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. Results: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. Conclusions: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.
Realistic Lenalidomide Dose Adjustment Strategy for Transplant-Ineligible Elderly Patients with Relapsed/Refractory Multiple Myeloma: Japanese Real-World Experience
Authors: Nakaya Aya , Fujita Shinya , Satake Atsushi , Nakanishi Takahisa , Azuma Yoshiko , Tsubokura Yukie , Hotta Masaaki , Yoshimura Hideaki , Ishii Kazuyoshi , Ito Tomoki , Nomura Shosaku
Published: July 2017

Lenalidomide is an immunomodulatory drug administered orally in the treatment of multiple myeloma. Some elderly patients require a reduced lenalidomide dose because of comorbidities and/or adverse events. This study investigated the actual dose of lenalidomide in elderly patients, finding that most received reduced (5-10 mg) doses. The most common reasons for dose reduction were renal dysfunction (54% of patients), fatigue (grade ≥3; 20%), hematologic disorder (grade ≥3; 14%), and rash (grade ≥3; 9%). Their median time to progression was 11.8 months and their median overall survival was 39.2 months. The overall response rate was 73%, including 17% with a complete response, 19% with a very good partial response, and 37% with a partial response. These results showed that, contrary to western countries, most patients were treated with a reduced dose of lenalidomide in Japan. However, it is suggested that continued treatment with a tolerable dose may yield favorable outcomes.
Quality in Colonoscopy: Beyond the Adenoma Detection Rate Fever
Authors: Taveira Filipe , Areia Miguel , Elvas Luís , Alves Susana , Brito Daniel , Saraiva Sandra , Cadime Ana Teresa
Published: July 2017

Background: Colonoscopy quality is a hot topic in gastroenterological communities, with several actual guidelines focusing on this aspect. Although the adenoma detection rate (ADR) is the single most important indicator, several other metrics are described and need reporting. Electronic medical reports are essential for the audit of quality indicators; nevertheless, they have proved not to be faultless. Aim: The aim of this study was to analyse and audit quality indicators (apart from ADR) using only our internal electronic endoscopy records as a starting point for improvement. Methods: An analysis of electronically recorded information of 8,851 total colonoscopies from a single tertiary centre from 2010 to 2015 was performed. Results: The mean patient age was 63.4 ± 8.5 years; 45.5% of them were female, and in 14.6% sedation was used. Photographic documentation was done in 98.4% with 10.7 photographs on average, and 37.4% reports had <8 pictures per exam. Bowel preparation was rated as adequate in 67%, fair in 27% and inadequate in 4.9% of cases. The adjusted caecal intubation rate (CIR) was 92%, while negative predictors were inadequate preparation (OR 119, 95% CI 84-170), no sedation (OR 2.39, 95% CI 1.81-3.15), female gender (OR 1.61, 95% CI 1.38-1.88) and age ≥65 years (OR 1.56, 95% CI 1.34-1.82). In 28% of patients, a snare polypectomy was performed, correlating with adequate preparation (OR 5.75, 95% CI 3.90-8.48), male gender (OR 1.82, 95% CI 1.64-2.01) and age ≥65 years (OR 1.25, 95% CI 1.13-1.37; p < 0.01) as positive predictors. An annual evolution was observed with improvements in photographic documentation (10.7 vs. 12.9; p < 0.001), CIR (91 vs. 94%; p = 0.002) and “adequate” bowel preparation (p = 0.004). Conclusions: There is much more to report than the ADR to ensure quality in colonoscopy practice. Better registry systematization and integrated software should be goals to achieve in the short term.
Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates
Authors: Kara Emrah , Manna Dipankar , Løset Åge , Schneider Eric L. , Craik Charles S. , Kanse Sandip M.
Published: July 2017

Factor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP. The representative FSAP-cleaved sequence obtained from the phage display method was Val-Leu-Lys-Arg-Ser (P4-P1’). The sequence X-Lys/Arg-Nle-Lys/Arg (P4-P1) was derived from the PS-SCL method. These results show a predilection for cleavage at a cluster of basic amino acids on the nonprime side. Quenched fluorescent substrate (Ala-Lys-Nle-Arg-AMC) (amino methyl coumarin) and (Ala-Leu-Lys-Arg-AMC) had a higher selectivity for FSAP compared to other proteases from the hemostasis system. These substrates could be used to measure FSAP activity in a complex biological system such as plasma. In histonetreated plasma there was a specific activation of pro-FSAP as validated by the use of an FSAP inhibitory antibody, corn trypsin inhibitor to inhibit Factor XIIa and hirudin to inhibit thrombin, which may account for some of the haemostasis-related effects of histones. These results will aid the development of further selective FSAP activity probes as well as specific inhibitors that will help to increase the understanding of the functions of FSAP in vivo.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Interdependence between osteoprotegerin and active von Willebrand factor in long-term cardiovascular mortality prediction in patients undergoing percutaneous coronary intervention
Authors: Siller-Matula Jolanta M. , Lang Irene M. , Schoergenhofer Christian , Roest Mark , Jilma Bernd
Published: July 2017

The interdependence of the predictive accuracy of serum osteoprotegerin (OPG) and von Willebrand factor (vWF) levels for long-term cardiovascular outcomes has not been investigated so far. This was a prospective observational cohort study in 361 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Baseline levels of OPG, vWF, active vWF (act vWF) and ristocetin cofactor activity (vWF:RICO) were measured. Cardiovascular mortality was recorded over a median of five years. OPG concentrations >3.7 µg/ml emerged as the strongest predictor of cardiovascular (CV) death: 30 % of patients died during the five-year follow-up in this group, as compared to 10 % in patients with OPG ≤3.7 µg/ml (p<0.001). Act vWF had a significant prognostic impact on CV mortality when OPG levels were low (≤3.7 µg/ml): patients with act vWF concentration >1 µg/ml died in 14 %, whereas those with act vWF values ≤1 µg/ml had a mortality rate of 1 % (p=0.015). We stratified patients into three groups: high OPG, low OPG/high act vWF and low OPG/low act vWF. Patients with high OPG values had a 13-fold higher risk for CV death than those with low OPG/low act vWF concentrations (adj. HR: 12.6; 95 %CI: 1.7–94.7; p=0.014), and a two-fold higher risk as compared to those patients with low OPG/high act vWF concentrations (adj. HR: 2.0; 95 %CI: 1.1–3.7; p=0.03) in the adjusted Cox regression analysis. In conclusion, elevated OPG at the time of PCI was a strong independent predictor of five-years cardiovascular mortality, whereas act vWF had a significant prognostic impact on CV mortality when OPG levels were low.