bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactic Acidosis in Diabetic Population: Is Metformin Implicated? Results of a Matched Case-Control Study Performed on the Type 2 Diabetes Population of Grenoble Hospital University
Authors: Lepelley Marion , Giai Joris , Yahiaoui Nassima , Chanoine Sébastien , Villier Céline
Published: February 2016

Introduction. To evaluate the strength of association between lactic acidosis (LA) and well-recognized risk factors for LA, particularly the weight of metformin.Methods. This study is a matched case-control analysis concerning the type 2 diabetes population from Grenoble Hospital University. Cases of LA were defined biologically with pH < 7.35 and lactates > 5 mmol/L. They were matched to 2 controls defined as type 2 diabetic inpatients who did not present a LA during the study period. We performed a conditional logistic regression.Results. We included 302 cases and 604 controls; mean age was 69.5 years (SD 11.93). Intercurrent diseases were significantly associated with LA. Chronic medical conditions had a minor impact on LA incidence, except hepatocellular dysfunction. Metformin was significantly associated with a higher LA probability in case of acute kidney injury (AKI) (OR = 1.79;pvalue = 0.020) but not in patients without AKI.Discussion and Conclusions. According to this study, metformin, compared to acute medical conditions, seemed not to be associated with LA in patients with type 2 diabetes; however in case of AKI, metformin may be associated with LA.
Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data
Authors: Li Cheng-Wei , Chen Bor-Sen
Published: February 2016

Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.
Fulminant Pseudomembranous Colitis Presenting as Sigmoid Stricture and Severe Polyposis with Clinical Response to Intracolonic Vancomycin
Authors: Cheung Sai Wah , Li Kin Kong
Published: February 2016

Clostridium difficileinfection (CDI) is the most common cause of antibiotic-associated diarrhea. Severe diseases carry significant morbidities such as septic shock, acute kidney injury, bowel perforation, and mortality. Immunocompromising conditions increase the risk of developing the disease but whether these individuals suffer a more fulminant course or warrant a more potent first-line treatment is still controversial issue. Hereby we report a case of a cirrhotic patient with life-threatening pseudomembranous colitis complicated by colonic stricture, initially refractory to standard treatment but with subsequent improvement on intracolonic vancomycin.
Inflammatory Bowel Disease and Skin Cancer: An Assessment of Patient Risk Factors, Knowledge, and Skin Practices
Authors: Kimmel Jessica N. , Taft Tiffany H. , Keefer Laurie
Published: February 2016

Objective. Patients with inflammatory bowel disease (IBD) are at increased risk from skin cancer. Aims include assessing IBD patients’ risk factors and knowledge of skin cancer and current skin protection practices to identify gaps in patient education regarding skin cancer prevention in IBD.Methods. IBD patients≥18 years were recruited to complete an online survey.Results. 164 patients (mean age 43.5 years, 63% female) with IBD (67% Crohn’s disease, 31% ulcerative colitis, and 2% indeterminate colitis) were included. 12% (n=19) of patients had a personal history and 34% (n=55) had a family history of skin cancer. Females scored better on skin protection (16.94/32 versus 14.53/32,P≤0.03) and awareness (35.16/40 versus 32.98/40,P≤0.03). Patients over 40 years old scored better on prevention (17.45/28 versus 15.35/28,P=0.03). Patients with skin cancer scored better on prevention (20.56/28 versus 15.75/28,P≤0.001) and skin protection (21.47/32 versus 15.33/32,P≤0.001). 61% of patients recognized the link between skin cancer and IBD.Conclusions. The majority of IBD patients are aware of the link between skin cancer and IBD; however, skin protection practices are suboptimal. This emphasizes the role of healthcare professionals in providing further education for skin cancer prevention in the IBD population.
Identification and Assessment of the Potential Allergenicity of 7S Vicilins in Olive (Olea europaeaL.) Seeds
Authors: Jimenez-Lopez Jose C. , Zafra Adoración , Palanco Lucía , Florido José Fernando , Alché Juan de Dios
Published: February 2016

Olive seeds, which are a raw material of interest, have been reported to contain 11S seed storage proteins (SSPs). However, the presence of SSPs such as 7S vicilins has not been studied. In this study, following a search in the olive seed transcriptome, 58 sequences corresponding to 7S vicilins were retrieved. A partial sequence was amplified by PCR from olive seed cDNA and subjected to phylogenetic analysis with other sequences. Structural analysis showed that olive 7S vicilin contains 9α-helixes and 22β-sheets. Additionally, 3D structural analysis displayed good superimposition with vicilin models generated fromPistaciaandSesamum. In order to assess potential allergenicity, T and B epitopes present in these proteins were identified by bioinformatic approaches. Different motifs were observed among the species, as well as some species-specific motifs. Finally, expression analysis of vicilins was carried out in protein extracts obtained from seeds of different species, including the olive. Noticeable bands were observed for all species in the 15–75 kDa MW interval, which were compatible with vicilins. The reactivity of the extracts to sera from patients allergic to nuts was also analysed. The findings with regard to the potential use of olive seed as food are discussed.
Dual-Band Patch Antenna Fed by Meandering Probe for Low Cross-Polarization
Authors: Zhao Xiao-Lan , Lin Quan Wei
Published: February 2016

This paper presents a dual-band patch antenna loaded with face-to-face U-shaped slots fed by a substrate-integrated meandering probe (SIM-probe). With the presence of U-shaped slots, two current paths are formed, which leads to the resonance modes at 2.4 and 3.65 GHz on the patch. The SIM-probe suppresses the unwanted cross-polarization radiations by providing out-of-phase vertical currents from vertical metallic vias. To verify our work, a prototype was fabricated and tested. The proposed antenna achieves the impedance bandwidths of 9.4% and 9% from the frequency range of 2.34–2.57 GHz and 3.5–3.83 GHz (for the reflection coefficient ≤ −10 dB) and obtains average gains of 5.8 dBi and 6.8 dBi at both bands. The cross-polarization level is below −20 dB. Measured results agree well with the simulation.
Two Alternative Methods to Measure the Radiated Emission in a Reverberation Chamber
Authors: Xu Qian , Huang Yi , Yuan Sheng , Xing Lei , Tian Zhihao
Published: February 2016

One of the most important applications of a reverberation chamber is for radiated power measurement. Two new alternative methods are proposed to measure the radiated power of equipment under test in a reverberation chamber in this paper. Traditionally, as stated in IEC 61000-4-21 standard, this measurement requires two antennas, a signal generator and a spectrum analyzer or receiver. However, it is found that if a signal generator is not available, a vector network analyzer can be used to complete the measurement. Furthermore, if only one antenna is available, by taking advantage of the enhanced backscattering effect, the measurement can still be completed. By incorporating the one- and/or two-antenna methods, the radiation efficiency of antennas is also considered. Measurements have been conducted to verify the proposed methods, the results from these three methods are compared, and a very good agreement is obtained. It is found that the two proposed methods are simpler than the conventional method.
Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report
Authors: Das Anirban , Pratap Abhishek
Published: February 2016

Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment.
A Controlled Study on the Correlation between Tear Film Volume and Tear Film Stability in Diabetic Patients
Authors: Eissa Iman M. , Khalil Noha M. , El-Gendy Heba A.
Published: February 2016

Purpose. To assess the tear film quantity and correlate it with the quality and stability of the tear film in diabetics and compare them to age matched controls.Introduction. Diabetes affects tear film parameters in multiple ways. Poor metabolic control and neuropathy are postulated factors. To further understand how diabetes affects tear film parameters this study was conducted.Subjects and Methods. Tear meniscus height was measured by anterior segment OCT, along with tear thinning time, a subtype of noninvasive tear break-up time, and blinking rate per minute which were all recorded for 22 diabetic patients. Correlations between these tear film parameters were studied and then compared to 16 age matched controls.Results. A statistically significant difference was found in blinking rate between the diabetic and the control group (P=0.002), with higher blinking rate among diabetics. All tear film parameters were negatively correlated with duration of diabetes. A positive correlation was found between tear film volume and stability.Conclusion. Diabetes affects the tear film in various ways. Diabetics should be examined for dry eye signs even in absence of symptoms which may be masked by associated neuropathy. Duration of diabetes has an impact on tear film status.
Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products
Authors: Sun Hong , Yuan Yang , Sun Zilin
Published: February 2016

Diabetic nephropathy (DN) caused by advanced glycation end products (AGEs) may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increases lipid accumulation in a human renal tubular epithelial cell line (HK-2) via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS). Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2) and liver X receptor (LXR), followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) mediated cholesterol synthesis and low density lipoprotein receptor (LDLr) mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.
Diabetic Microangiopathy Is an Independent Predictor of Incident Diabetic Foot Ulcer
Authors: Tomita Masuomi , Kabeya Yusuke , Okisugi Mari , Katsuki Takeshi , Oikawa Yoichi , Atsumi Yoshihito , Matsuoka Kempei , Shimada Akira
Published: February 2016

Aim.To determine the diabetic foot ulcer incidence and examine its association with microangiopathy complications, including diabetic retinopathy (DR) and albuminuria (Alb), in type 2 diabetes patients.Methods.This was a retrospective cohort study of 1,305 patients with type 2 diabetes who were assigned to the following groups: Category 1, normoalbuminuria without DR (n=712); Category 2, Alb without DR (n=195); Category 3, normoalbuminuria with DR (n=185); and Category 4, Alb with DR (n=213). Cox proportional hazard models were used to compare the risks of developing diabetic foot ulcers across the categories.Results. During 14,249 person-years of follow-up, 50 subjects developed diabetic foot ulcers, with incidence rates of 1.6/1,000, 1.5/1,000, 3.4/1,000, and 12.5/1,000 person-years in Categories 1, 2, 3, and 4, respectively. After adjusting for the presence of diabetic neuropathy and macroangiopathy, the hazard ratios and 95% confidence intervals (CIs) for the risk of diabetic foot ulcer development were 0.66 (95% CI, 0.18–2.36), 1.72 (95% CI, 0.67–4.42), and 3.17 (95% CI, 1.52–6.61) in Categories 2, 3, and 4, respectively, compared with Category 1.Conclusion. The presence of DR and Alb significantly increases the risk of diabetic foot ulcer development.
Photocatalytic Reduction of CO2Using TiO2-Graphene Nanocomposites
Authors: Liu Jinghua , Niu Yinghua , He Xiong , Qi Jingyao , Li Xin
Published: February 2016

TiO2-graphene (TiO2-RGO) nanocomposites were preparedviaa simple chemical method by using graphene oxide (GO) and TiO2nanoparticles as starting materials. The morphologies and structural properties of the as-prepared composites were characterized by X-ray diffraction, Raman spectroscopy, N2adsorption-desorption measurements, and transmission electron microscopy. TiO2-RGO nanocomposites exhibited great photocatalytic activity toward reduction of CO2into CH4(2.10 μmol g−1 h−1) and CH3OH (2.20 μmol g−1 h−1), which is attributed to the synergistic effect between TiO2and graphene.
About the Existence Results of Fractional Neutral Integrodifferential Inclusions with State-Dependent Delay in Fréchet Spaces
Authors: Suganya Selvaraj , Baleanu Dumitru , Selvarasu Siva , Arjunan Mani Mallika
Published: February 2016

A recent nonlinear alternative for multivalued contractions in Fréchet spaces thanks to Frigon fixed point theorem consolidated with semigroup theory is utilized to examine the existence results for fractional neutral integrodifferential inclusions (FNIDI) with state-dependent delay (SDD). An example is described to represent the hypothesis.
Collaborative Management of Complex Major Construction Projects: AnyLogic-Based Simulation Modelling
Authors: Zhao Na , An Shi
Published: February 2016

Complex supply chain system collaborative management of major construction projects effectively integrates the different participants in the construction project. This paper establishes a simulation model based on AnyLogic to reveal the collaborative elements in the complex supply chain management system and the modes of action as well as the transmission problems of the intent information. Thus it is promoting the participants to become an organism with coordinated development and coevolution. This study can help improve the efficiency and management of the complex system of major construction projects.
Bach1 Induces Endothelial Cell Apoptosis and Cell‐Cycle Arrest through ROS Generation
Authors: Wang Xinhong , Liu Junxu , Jiang Li , Wei Xiangxiang , Niu Cong , Wang Rui , Zhang Jianyi , Meng Dan , Yao Kang
Published: February 2016

The transcription factor BTB and CNC homology 1 (Bach1) regulates genes involved in the oxidative stress response and cell‐cycle progression. We have recently shown that Bach1 impairs cell proliferation and promotes apoptosis in cultured endothelial cells (ECs), but the underlying mechanisms are largely uncharacterized. Here we demonstrate that Bach1 upregulation impaired the blood flow recovery from hindlimb ischemia and this effect was accompanied both by increases in reactive oxygen species (ROS) and cleaved caspase 3 levels and by declines in the expression of cyclin D1 in the injured tissues. We found that Bach1 overexpression induced mitochondrial ROS production and caspase 3‐dependent apoptosis and its depletion attenuated H2O2‐induced apoptosis in cultured human microvascular endothelial cells (HMVECs). Bach1‐induced apoptosis was largely abolished when the cells were cultured with N‐acetyl‐l‐cysteine (NAC), a ROS scavenger. Exogenous expression of Bach1 inhibited the cell proliferation and the expression of cyclin D1, induced an S‐phase arrest, and increased the expression of cyclin E2, which were partially blocked by NAC. Taken together, our results suggest that Bach1 suppresses cell proliferation and induces cell‐cycle arrest and apoptosis by increasing mitochondrial ROS production, suggesting that Bach1 may be a promising treatment target for the treatment of vascular diseases.
DNA Tumor Viruses and Cell Metabolism
Authors: Mushtaq Muhammad , Darekar Suhas , Kashuba Elena
Published: February 2016

Viruses play an important role in cancerogenesis. It is estimated that approximately 20% of all cancers are linked to infectious agents. The viral genes modulate the physiological machinery of infected cells that lead to cell transformation and development of cancer. One of the important adoptive responses by the cancer cells is their metabolic change to cope up with continuous requirement of cell survival and proliferation. In this review we will focus on how DNA viruses alter the glucose metabolism of transformed cells. Tumor DNA viruses enhance “aerobic” glycolysis upon virus‐induced cell transformation, supporting rapid cell proliferation and showing the Warburg effect. Moreover, viral proteins enhance glucose uptake and controls tumor microenvironment, promoting metastasizing of the tumor cells.
A Case Report of Dramatically Increased Thyroglobulin after Lymph Node Biopsy in Thyroid Carcinoma after Total Thyroidectomy and Radioiodine
Authors: Moosavi Mandana , Kreisman Stuart
Published: February 2016

Thyroglobulin (Tg) is an important modality for monitoring patients with thyroid cancers, especially after thyroidectomy followed by radioiodine (RAI). It is also used as a marker for burden of thyroid tissue whether malignant or benign. Although there have been several reports of rising serum Tg transiently after thyroid biopsy in intact glands and following palpation or trauma, there are no reports in the literature of elevation in Tg after biopsy of suspicious lesions in thyroidectomized patients. In this paper we report a fascinating case of a considerable and initially worrying, although ultimately transient, rise in Tg in a patient 2 years after total thyroidectomy and RAI ablation after fine needle aspiration (FNA) of a suspicious thyroid bed nodule that was proven positive.
Unsteady MHD Mixed Convection Flow of Chemically Reacting Micropolar Fluid between Porous Parallel Plates with Soret and Dufour Effects
Authors: Ojjela Odelu , Naresh Kumar N.
Published: February 2016

The objective of the present study is to investigate the first-order chemical reaction and Soret and Dufour effects on an incompressible MHD combined free and forced convection heat and mass transfer of a micropolar fluid through a porous medium between two parallel plates. Assume that there are a periodic injection and suction at the lower and upper plates. The nonuniform temperature and concentration of the plates are assumed to be varying periodically with time. A suitable similarity transformation is used to reduce the governing partial differential equations into nonlinear ordinary differential equations and then solved numerically by the quasilinearization method. The fluid flow and heat and mass transfer characteristics for various parameters are analyzed in detail and shown in the form of graphs. It is observed that the concentration of the fluid decreases whereas the temperature of the fluid enhances with the increasing of chemical reaction and Soret and Dufour parameters.
Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice
Authors: Mohamed Hanan R. H. , Hussien Nahed A.
Published: February 2016

Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500 mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at 24 h, 7 days, or 14 days after the last treatment. The present results report that exposure to TiO2NPs produces mild to moderate changes in the cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to inherited forms of the Alzheimer’s disease. Therefore, from these findings, the present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimer’s disease incidence.
Experimentally Induced Pulpal Lesion and Substance P Expression: Effect of Ketoprofen—A Preliminary Study
Authors: Abbate Gian Marco , Sacerdote Paola , Amodeo Giada , Mangano Alessandro , Levrini Luca
Published: February 2016

Objectives.To evaluate substance P (SP) and the effect of ketoprofen administration, a nonsteroidal anti-inflammatory drug (NSAID), on SP in the pulp of upper third molars with experimentally induced pulpal lesion.Materials and Methods.A sample of 20 young systemically healthy adults of both sexes, nonsmokers, with a healthy upper third molar to extract for orthodontic purposes, was selected. Prior to the procedure, an inflammatory process was generated by mechanical exposure of the pulp. After 15 minutes, the pulp was collected using a sterile barbed broach. SP levels were determined by using a commercially available enzyme immunoassay (ELISA) kit. The subjects were randomly divided into two groups: group 1 received a dose of ketoprofen 30 minutes prior to the experimental procedure. The subjects of group 2 did not receive any kind of drug administration. The patients were asked to complete a diary on the postoperative pain.Results.No statistically significant difference could be detected in SP expression between the two groups. In group 1, pain manifestation was significantly delayed in comparison with group 2.Conclusions.Preventive administration of ketoprofen did not significantly affect the pulpal levels of SP but resulted in a significantly postponed manifestation of pain after extraction.
Rhabdomyolysis following Cardiac Surgery: A Prospective, Descriptive, Single-Center Study
Authors: Omar Amr S. , Ewila Hesham , Aboulnaga Sameh , Tuli Alejandro Kohn , Singh Rajvir
Published: February 2016

Purpose. Rhabdomyolysis (RML) following cardiac surgery and its relationship with acute kidney injury (AKI) require investigation.Patients and Methods. All patients undergoing cardiac surgery in our hospital were enrolled in this prospective study during a 1-year period. To investigate the occurrence of RML and its association with AKI, all patients in the study underwent serial assessment of serum creatine kinase (CK) and myoglobin levels. Serial renal function, prior statin treatment, and outcome variables were recorded.Results. In total, 201 patients were included in the study: 185 men and 16 women with a mean age of52.0±12.4years. According to the presence of RML (CK of ≥2,500 U/L), the patients were divided into Group I (RML present in 17 patients) and Group II (RML absent in 184 patients). Seven patients in Group I had AKI (41%) where 34 patients in group II had AKI (18.4%),P=0.025. We observed a significantly longer duration of ventilation, length of stay in the ICU, and hospitalization in Group I (P<0.001for all observations).Conclusions. An early elevation of serum CK above 2500 U/L postoperatively in high-risk cardiac surgery could be used to diagnose RML that may predict the concomitance of early AKI.
A Hybrid Interpolation Method for Geometric Nonlinear Spatial Beam Elements with Explicit Nodal Force
Authors: Fang Huiqing , Qi Zhaohui
Published: February 2016

Based on geometrically exact beam theory, a hybrid interpolation is proposed for geometric nonlinear spatial Euler-Bernoulli beam elements. First, the Hermitian interpolation of the beam centerline was used for calculating nodal curvatures for two ends. Then, internal curvatures of the beam were interpolated with a second interpolation. At this point, C1 continuity was satisfied and nodal strain measures could be consistently derived from nodal displacement and rotation parameters. The explicit expression of nodal force without integration, as a function of global parameters, was founded by using the hybrid interpolation. Furthermore, the proposed beam element can be degenerated into linear beam element under the condition of small deformation. Objectivity of strain measures and patch tests are also discussed. Finally, four numerical examples are discussed to prove the validity and effectivity of the proposed beam element.
Nucleolar PARP-1 Expression Is Decreased in Alzheimer’s Disease: Consequences for Epigenetic Regulation of rDNA and Cognition
Authors: Zeng Jianying , Libien Jenny , Shaik Fatima , Wolk Jason , Hernández A. Iván
Published: February 2016

Synaptic dysfunction is thought to play a major role in memory impairment in Alzheimer’s disease (AD). PARP-1 has been identified as an epigenetic regulator of plasticity and memory. Thus, we hypothesize that PARP-1 may be altered in postmortem hippocampus of individuals with AD compared to age-matched controls without neurologic disease. We found a reduced level of PARP-1 nucleolar immunohistochemical staining in hippocampal pyramidal cells in AD. Nucleolar PARP-1 staining ranged from dispersed and less intense to entirely absent in AD compared to the distinct nucleolar localization in hippocampal pyramidal neurons in controls. In cases of AD, the percentage of hippocampal pyramidal cells with nucleoli that were positive for both PARP-1 and the nucleolar marker fibrillarin was significantly lower than in controls. PARP-1 nucleolar expression emerges as a sensitive marker of functional changes in AD and suggests a novel role for PARP-1 dysregulation in AD pathology.
Studies of the Effectiveness of Bisphosphonate and Vanadium‐Bisphosphonate Compounds In Vitro against Axenic Leishmania tarentolae
Authors: Christensen Amy T. , McLauchlan Craig C. , Dolbecq Anne , Mialane Pierre , Jones Marjorie A.
Published: February 2016

Leishmaniasis is a disease that is a significant problem for people, especially in tropical regions of the world. Current drug therapies to treat the disease are expensive, not very effective, and/or of significant side effects. A series of alkyl bisphosphonate compounds and one amino bisphosphonate compound, as well as alendronate and zoledronate, were tested as potential agents against Leishmania tarentolae. Also, two polyoxometalates (POMs) with nitrogen‐containing bisphosphonate ligands, vanadium/alendronate (V5(Ale)2) and vanadium/zoledronate (V3(Zol)3), were tested against L. tarentolae and compared to the results of the alendronate and zoledronate ligands alone. Of the compounds evaluated in this study, the V5(Ale)2 and V3(Zol)3 complexes were most effective in inhibiting the growth of L. tarentolae. The V5(Ale)2 complex had a larger impact on cell growth than either alendronate or orthovanadate alone, whereas zoledronate itself has a significant effect on cell growth, which may contribute to the activity of the V3(Zol)3 complex.
Preventive Effects of the Chinese Herbal Medicine Prescription Tangkuei Decoction for Frigid Extremities on Sciatic Neuropathy in Streptozotocin‐Induced Diabetic Rats
Authors: Liu Pengsong , Bian Yuanyuan , Zhang Hong , Jia Aiming
Published: February 2016

Ischemia and hypoxia are important physiological changes in diabetic peripheral neuropathy (DPN). Chinese herbal medicine prescription Tangkuei Decoction for Frigid Extremities (TDFE) is useful for increasing blood flow. To help determine whether TDFE could protect the peripheral nerves of diabetic patients from the degeneration caused by high blood glucose, TDFE was administered to streptozotocin‐induced diabetic rats for 6 or 12 weeks. Plantar thermal stimulation reaction time thresholds, sciatic nerve conduction velocities, and the levels of HIF‐1α mRNA, HIF‐1α protein, VEGF protein, and the endothelial marker vWF in sciatic nerves were measured at the end of the sixth and twelfth weeks. The thermal thresholds and sciatic nerve conduction velocities of the rats differed after 12 weeks, and the sciatic nerves of the diabetic rats that were given TDFE displayed higher levels of HIF‐1α protein, VEGF protein, and HIF‐1α mRNA than those of the diabetic model rats. The results at 6 weeks differed from those at 12 weeks. These results suggest that the early preventive application of TDFE effectively delayed the development of DPN and that TDFE increased HIF‐1α mRNA levels in the sciatic nerves of diabetic rats through 12 weeks of treatment.
Rheological Characterization of Warm-Modified Asphalt Mastics Containing Electric Arc Furnace Steel Slags
Authors: Pasetto M. , Baliello A. , Giacomello G. , Pasquini E.
Published: February 2016

The environmental sustainability of road materials and technologies plays a key role in pavement engineering. In this sense, the use of Warm Mix Asphalt (WMA), that is, a modified asphalt concrete that can be produced and applied at lower temperature, is considered an effective solution leading to environmental and operational benefits. The environmental sustainability of WMA can be further enhanced with the inclusion of steel slag in partial substitution of natural aggregates. Nevertheless, such innovative material applied at lower temperatures containing warm additives and steel slag should be able to guarantee at least the same performance of traditional hot mix asphalts, thus assuring acceptable mechanical properties and durability. Therefore, the purpose of this study is to investigate the rheological behaviour of bituminous mastics obtained combining a warm-modified binder and a filler (material passing to 0.063 mm) coming from electric arc furnace steel slag. To evaluate the influence of both warm additive and steel slag, a plain binder and limestone filler were also used for comparison purposes. Complex modulus and permanent deformation resistance of bitumens and mastics were assessed using a dynamic shear rheometer. Experimental results showed that steel slag warm mastics assure enhanced performance demonstrating promising applicability.
Angle Modulated Artificial Bee Colony Algorithms for Feature Selection
Authors: Yavuz Gürcan , Aydin Doğan
Published: February 2016

Optimal feature subset selection is an important and a difficult task for pattern classification, data mining, and machine intelligence applications. The objective of the feature subset selection is to eliminate the irrelevant and noisy feature in order to select optimum feature subsets and increase accuracy. The large number of features in a dataset increases the computational complexity thus leading to performance degradation. In this paper, to overcome this problem, angle modulation technique is used to reduce feature subset selection problem to four-dimensional continuous optimization problem instead of presenting the problem as a high-dimensional bit vector. To present the effectiveness of the problem presentation with angle modulation and to determine the efficiency of the proposed method, six variants of Artificial Bee Colony (ABC) algorithms employ angle modulation for feature selection. Experimental results on six high-dimensional datasets show that Angle Modulated ABC algorithms improved the classification accuracy with fewer feature subsets.
Study of Valproic Acid-Enhanced Hepatocyte Steatosis
Authors: Chang Renin , Chou Mei-Chia , Hung Li-Ying , Wang Mu-En , Hsu Meng-Chieh , Chiu Chih-Hsien
Published: February 2016

Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-basedin vitromodel. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1 (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were increased, that of carnitine palmitoyltransferase Ia(Cpt1a) was not affected, and those of acetyl-Co A carboxylaseα(Acca) and fatty acid synthase (Fasn) were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptorγ(PPARγ) nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation.
Antibacterial Activity of Partially Oxidized Ag/Au Nanoparticles against the Oral PathogenPorphyromonas gingivalisW83
Authors: Holden Megan S. , Black Jason , Lewis Ainsely , Boutrin Marie-Claire , Walemba Elvin , Sabir Theodore S. , Boskovic Danilo S. , Wilson Aruni , Fletcher Hansel M. , Perry Christopher C.
Published: February 2016

Advances in nanotechnology provide opportunities for the prevention and treatment of periodontal disease. While physicochemical properties of Ag containing nanoparticles (NPs) are known to influence the magnitude of their toxicity, it is thought that nanosilver can be made less toxic to eukaryotes by passivation of the NPs with a benign metal. Moreover, the addition of other noble metals to silver nanoparticles, in the alloy formulation, is known to alter the silver dissolution behavior. Thus, we synthesized glutathione capped Ag/Au alloy bimetallic nanoparticles (NPs)viathe galvanic replacement reaction between maltose coated Ag NPs and chloroauric acid (HAuCl4) in 5% aqueous triblock F127 copolymer solution. We then compared the antibacterial activity of the Ag/Au NPs to pure Ag NPs onPorphyromonas gingivalisW83, a key pathogen in the development of periodontal disease. Only partially oxidized glutathione capped Ag and Ag/Au (Au : Ag ≈ 0.2) NPs inhibited the planktonic growth ofP. gingivalisW83. This effect was enhanced in the presence of hydrogen peroxide, which simulates the oxidative stress environment in the periodontal pocket during chronic inflammation.
Dense Trajectories and DHOG for Classification of Viewpoints from Echocardiogram Videos
Authors: Huang Liqin , Zhang Xiangyu , Li Wei
Published: February 2016

In echo-cardiac clinical computer-aided diagnosis, an important step is to automatically classify echocardiography videos from different angles and different regions. We propose a kind of echocardiography video classification algorithm based on the dense trajectory and difference histograms of oriented gradients (DHOG). First, we use the dense grid method to describe feature characteristics in each frame of echocardiography sequence and then track these feature points by applying the dense optical flow. In order to overcome the influence of the rapid and irregular movement of echocardiography videos and get more robust tracking results, we also design a trajectory description algorithm which uses the derivative of the optical flow to obtain the motion trajectory information and associates the different characteristics (e.g., the trajectory shape, DHOG, HOF, and MBH) with embedded structural information of the spatiotemporal pyramid. To avoid “dimension disaster,” we apply Fisher’s vector to reduce the dimension of feature description followed by the SVM linear classifier to improve the final classification result. The average accuracy of echocardiography video classification is 77.12% for all eight viewpoints and 100% for three primary viewpoints.
Impact of Continuous Erythropoietin Receptor Activator on Selected Biomarkers of Cardiovascular Disease and Left Ventricle Structure and Function in Chronic Kidney Disease
Authors: Bartnicki Piotr , Rysz Jacek , Franczyk Beata , Baj Zbigniew , Majewska Ewa
Published: February 2016

Background. Cardiovascular morbidity and mortality are very high in patients with chronic kidney disease (CKD). The purpose of this study is to evaluate the impact of continuous erythropoietin receptor activator (CERA) on selected biomarkers of cardiovascular disease, left ventricle structure, and function in CKD. Material and Methods. Peripheral blood was collected from 25 CKD patients before and after CERA treatment and 20 healthy subjects. In serum samples, we assessed inflammatory markers (IL‐1β, TNF‐RI, TNF‐RII, sFas, sFasL, MMP‐9, TIMP‐1, and TGF‐β1), endothelial dysfunction markers (sE‐selectin, sICAM‐1, and sVCAM‐1), and volume‐related marker (NT‐proBNP). All subjects underwent echocardiography and were evaluated for selected biochemical parameters (Hb, creatinine, and CRP). Results. Evaluated biomarkers and echocardiographic parameters of left ventricle structure were significantly increased but left ventricle EF was significantly decreased in CKD patients compared to controls. After CERA treatment, we observed a significant increase of Hb and left ventricle EF and a significant decrease of NT‐proBNP and MMP‐9. There was a significant negative correlation between Hb and TNF‐RI, sICAM‐1, and IL‐1β. Conclusions. Our results indicate that selected biomarkers related to cardiovascular risk are significantly increased in CKD patients compared to controls. CERA treatment has anti‐inflammatory action, diminishes endothelial dysfunction, and improves left ventricle function in these patients.
Acute Cytomegalovirus Hepatitis in an Immunocompetent Host as a Reason for Upper Right Abdominal Pain
Authors: Jensen Kai Oliver , Angst Eliane , Hetzer Franc Heinrich , Gingert Christian
Published: February 2016

Cytomegalovirus infections are widely distributed with a seroprevalence of up to 100%. The majority of the cases take a silent course or deal with unspecific clinical symptoms. Complications in immunocompetent patients are rare but may affect the liver and lead up to an acute organ failure. In this case report, we describe a 35-year-old immunocompetent female with an acute cytomegalovirus infection presenting as acute hepatitis with ongoing upper right abdominal pain after cholecystectomy. Upper right abdominal pain is a common symptom with a wide range of differential diagnoses. If common reasons can be excluded, we want to sensitize for cytomegalovirus infection as a minor differential diagnosis even in immunocompetent patients.
Gemcitabine-Induced Subacute Cutaneous Lupus Erythematosus: A Case Report
Authors: Ben Zvi Masha , Vaknine Hananya , Menczer Joseph , Peled Ofri , Ben Shem Erez , Schreiber Letizia , Levy Tally
Published: February 2016

Subacute cutaneous lupus erythematosus (SCLE) is a rare eruption related to several pharmacological and chemotherapy agents. We present a 63-year-old female with recurrent epithelial ovarian cancer who developed SCLE after administration of gemcitabine. Following discontinuation of gemcitabine and after oral steroid treatment, all skin lesions disappeared. In view of the extensive use of gemcitabine in recurrent ovarian cancer, it is important to be aware of the possibility of SCLE occurrence in these patients.
Evolution of the SRGAP2 Gene Is Linked to Intelligence in Mammals
Authors: Tiwary Basant K.
Published: February 2016

Background/Aims: A recent duplication of the gene encoding SLIT-ROBO Rho GTPase-activating protein 2 (SRGAP2) in the primate lineage has been proposed to be associated with the human-specific extraordinary development of intelligence. There is no report regarding the role of the SRGAP2 gene in the expression of neural traits indicating intelligence in mammals. Methods: A phylogenetic tree of the SRGAP2 gene from 11 mammals was reconstructed using MrBayes. The evolution of neural traits along the branches of the phylogenetic tree was modeled in the BayesTraits, and the dN/dS ratio (i.e. the ratio between the number of nonsynonymous substitutions per nonsynonymous site and the number of synonymous substitutions per synonymous site) was estimated using the codon-based maximum likelihood method (CODEML) in PAML (phylogenetic analysis by maximum likelihood). Results: Two neural traits, namely brain mass and the number of cortical neurons, showed statistical dependency on the underlying evolutionary history of the SRGAP2 gene in mammals. A significant positive correlation between the increase in cortical neurons and the rate of nucleotide substitutions in the SRGAP2 gene was observed concomitantly with a significant negative correlation between the increase in cortical neurons and the rate of nonsynonymous substitutions in the gene. The SRGAP2 gene appears to be under intense pressure of purifying selection in all mammalian lineages under stringent functional constraint. Conclusion: This work indicates a key role of the SRGAP2 gene in the rapid expansion of neurons in the brain cortex, thereby facilitating the evolution of remarkable intelligence in mammals.
HbA1c Levels and Long-Term Mortality in Patients Undergoing Coronary Angiography
Authors: Havakuk Ofer , Banai Shmuel , Halkin Amir , Konigstein Maayan , Ben Assa Eyal , Berliner Shlomo , Ziv-Baran Tomer , Elbaz Meital , Revivo Miri , Keren Gad , Finkelstein Ariel , Arbel Yaron
Published: February 2016

Objectives: Previous studies investigating the prognostic value of HbA1c in patients undergoing coronary angiography reported a mixed pattern of results. Therefore, we aimed to better define the prognostic power of HbA1c among coronary catheterized patients. Methods: Patients undergoing coronary angiography (n = 3,749) were divided into four groups according to HbA1c levels (<5, 5-6, 6-7 and >7%). Cox regression models assessed long-term mortality after adjusting for multiple covariates. Results: Baseline clinical profiles differed in HbA1c groups, with a higher prevalence of comorbidities in the groups with higher HbA1c levels. Median follow-up was 1,745 days (interquartile range 1,007-2,171). A J-shaped association curve was observed between HbA1c levels and all-cause mortality rates, with patients in the lowest and highest HbA1c groups suffering from significantly higher mortality rates compared to in-between groups (hazard ratio 1.9, 95% CI 1.32-2.74, p = 0.001, and hazard ratio 1.58, 95% CI 1.29-1.95, p < 0.001, for the lowest and highest HbA1c groups, respectively). This association persisted after adjustment for anemia, nutritional status, renal function, cardiovascular risk factors and inflammatory biomarkers. Conclusions: HbA1c levels <5 or >7% are predictors of all-cause mortality in patients undergoing coronary angiography.
The Effectiveness of Intravitreal Ranibizumab in Patients with Diabetic Macular Edema Who Have Failed to Respond to Intravitreal Bevacizumab
Authors: Ehrlich Rita , Dan Idit , Deitch Iris , Axer-Siegel Ruth , Mimouni Karin
Published: February 2016

Purpose: To investigate the response to intravitreal ranibizumab after failure of intravitreal bevacizumab in patients with diabetic macular edema (DME). Methods: Demographics, visual acuity (VA), central macular thickness (CMT), and HbA1C were retrospectively collected from DME patients treated with second-line intravitreal ranibizumab at a tertiary hospital in 2012-2013 and followed for at least 3 months. Results: Twenty-two patients (26 eyes) were included in the study, with a mean (±SD) age of 66 ± 8.1 years and followed for an average of 28.36 months. The mean number of intravitreal bevacizumab injections was 7.3 ± 2.8, and of intravitreal ranibizumab injections 5.11 ± 2.4. After 3 ranibizumab injections, 57% of eyes showed improvement in VA. The change in VA was statistically significant (p = 0.044) in those eyes where the pretreatment acuity for the second-line therapy was <20/40 (logMAR 0.3). CMT decreased from 435.95 ± 83.28 to 373.69 ± 44.39 µm (p = 0.01). The number of ranibizumab injections was significantly correlated with the change in CMT (p = 0.037). Conclusion: Intravitreal treatment with ranibizumab can be efficacious in eyes with DME that have failed to respond to bevacizumab.
The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort
Authors: Spalinger Marianne R. , Voegelin Marius , Biedermann Luc , Zeitz Jonas , Rossel Jean-Benoit , Sulz Michael Christian , Frei Pascal , Scharl Sylvie , Vavricka Stephan R. , Fried Michael , Rogler Gerhard , Scharl Michael ,   for the Swiss IBD Cohort Study Group
Published: February 2016

Background/Aims: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. Methods: One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes ‘homozygous wild-type' (TT), ‘heterozygous' (CT) and ‘homozygous variant' (CC). Results: About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. Conclusion: IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.