bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potential Role of Hemopexin and Heme Oxygenase-1 Inducer in a Model of Sepsis
Authors: Hassaan Passainte S. , Mehanna Radwa A. , Dief Abeer E.
Published: September 2015

Background and Aims. Sepsis can evoke disseminated intravascular coagulation, resulting in multiple organ failure and death. Heme oxygenase-1 (HO-1) and hemopexin (HPx) can mediate cytoprotective mechanisms against these deleterious effects. This study aims to determine a role for HO-1 and HPx in coagulopathy induced by septic inflammation and define whether they can enhance the production of anti-inflammatory cytokine IL-10. Materials and Methods. 48 healthy male albino rats were divided equally into 4 groups: control group: animals subjected to laparotomy and bowel manipulation; CLP group: severe sepsis induced by cecal ligation puncture (CLP); CLP + hemin group: animals received single intraperitoneal injection of hemin (50 µmol/kg) 12 h before sepsis induction; CLP + HPx group: animals received single HPx dose (150 µg/rat, i.v.) 30 min before sepsis induction. Survival rates were calculated. Prothrombin time (PT), activated partial thromboplastin time (APTT), and activated protein C (APC), liver HO-1, serum, and liver IL-10 levels were measured, 48 hrs after sepsis induction. Liver and lung were excised for histopathological examination. Results. Hemin and HPx administration upregulated liver HO-1 and IL-10. They prolonged PT, PTT and increased APC. They reduced the inflammatory infiltrate and thrombosis in liver and lung parenchyma. However, hemin was superior in controlling coagulopathy and HO-1 production, while HPx was more potent stimulant of IL-10 expression. Conclusions. Hemin and HPx have a potential beneficial effect in severe sepsis regarding coagulopathy and inflammation.
Intracellular Cleavage of the Cx43 C‐Terminal Domain by Matrix‐Metalloproteases: A Novel Contributor to Inflammation?
Authors: De Bock Marijke , Wang Nan , Decrock Elke , Bultynck Geert , Leybaert Luc
Published: September 2015

The coordination of tissue function is mediated by gap junctions (GJs) that enable direct cell‐cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx) proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs) in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein‐protein interactions and posttranslational modifications that predominantly take place in the C‐terminal domain of Cx43. Matrix metalloproteases (MMPs) are a major group of zinc‐dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP‐Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C‐terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.
Functional Outcomes: One Year after a Cardiac Arrest
Authors: Raina Ketki D. , Rittenberger Jon C. , Holm Margo B. , Callaway Clifton W.
Published: September 2015

Objective. The study aim was to characterize the time-course of recovery in impairments, activity limitations, participation restrictions, disability, and quality of life during the first year after cardiac arrest. Secondarily, the study described the associations between the instruments used to measure each of these domains.Methods. Measures of global disability (Cerebral Performance Category, CPC, Modified Rankin Scale, mRS), quality of life, activity limitations, participation restrictions, and affective and cognitive impairments were administered to 29 participants 1, 6, and 12 months after cardiac arrest.Results. Global measures of disability indicated recovery between one month and one year after cardiac arrest (mean CPC: 2.1 versus 1.69,  P<0.05; mean mRS: 2.55 versus 1.83,P<0.05). While global measures of disability were moderately associated with participation, they were poorly associated with other measures. The cohort endorsed depressive symptomatology throughout the year but did not have detectable cognitive impairment.Conclusions. Recovery from cardiac arrest is multifaceted and recovery continues for months depending upon the measures being used. Measures of global disability, reintegration into the community, and quality of life yield different information. Future clinical trials should include a combination of measures to yield the most complete representation of recovery after cardiac arrest.
Rational-Like Solutions of a Differential-Difference Equation Related to Ablowitz-Ladik Spectral Problem
Authors: Zhang Jiang-ping , Li Qi , Chen Shou-ting
Published: September 2015

By using the Casoratian technique, we construct the double Casoratian solutions whose entries satisfy matrix equation of a differential-difference equation related to the Ablowitz-Ladik spectral problem. Soliton solutions and rational-like solutions are obtained from taking special cases in general solutions.
Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression in Alveolar Epithelial Cells
Authors: Maloney James P. , Gao Li
Published: September 2015

Vascular endothelial growth factor (VEGF) is an endothelial permeability mediator that is highly expressed in lung epithelium. In nonlung cells proinflammatory cytokines have been shown to increase VEGF expression, but their effects on lung epithelium remain unclear. We hypothesized that increases in alveolar epithelial cell VEGF RNA and protein expression occur after exposure to proinflammatory cytokines. We tested this using human alveolar epithelial cells (A549) stimulated with 5 proinflammatory cytokines. VEGF RNA expression was increased 1.4–2.7‐fold in response to IL‐1, IL‐6, IL‐8, TNF‐α, or TGF‐β over 6 hours, with TGF‐β having the largest response. TNF‐α increased VEGF RNA as early as 1 hour. A mix of IL‐1, IL‐6, and IL‐8 had effects similar to IL‐1. TNF‐α increased protein expression as early as 4 hours and had a sustained effect at 16 hours, whereas IL‐1 did not increase protein expression. Only VEGF165 was present in cultured A549 cells, yet other isoforms were seen in human lung tissue. Increased expression of VEGF in alveolar epithelial cells occurs in response to proinflammatory cytokines. Increased VEGF expression likely contributes to the pathogenesis of inflammatory lung diseases and to the angiogenic phenotype of lung cancer, a disease typically preceded by chronic inflammation.
Reconstruction of a Large Anterior Ear Defect after Mohs Micrographic Surgery with a Cartilage Graft and Postauricular Revolving Door Flap
Authors: Nemir Stephanie , Hunter-Ellul Lindsey , Codrea Vlad , Wagner Richard
Published: September 2015

A novel postauricular revolving door island flap and cartilage graft combination was employed to correct a large defect on the anterior ear of an 84-year-old man who underwent Mohs micrographic surgery for an antihelical squamous cell carcinoma. The defect measured 4.6 × 2.4 cm and spanned the antihelix, scapha, a small portion of the helix, and a large segment of underlying cartilage, with loss of structural integrity and anterior folding of the ear. The repair involved harvesting 1.5 cm2of exposed cartilage from the scaphoid fossa and then sculpting and suturing it to the remnant of the antihelical cartilage in order to recreate the antihelical crura. The skin of the posterior auricle was then incised just below the helical rim and folded anteriorly to cover the cartilage graft. The flap remained attached by a central subcutaneous pedicle, and an island designed using the full-thickness defect as a stencil template was pulled through the cartilage window anteriorly to resurface the anterior ear. This case demonstrates the use of the revolving door flap for coverage of large central ear defects with loss of cartilaginous support and illustrates how cartilage grafts may be used in combination with the flap to improve ear contour after resection.
Medical History of Elderly Patients in the Emergency Setting: Not an Easy Point-of-Care Diagnostic Marker
Authors: Lindner Tobias , Slagman Anna , Senkin Arthur , Möckel Martin , Searle Julia
Published: September 2015

Background. Medical histories are a crucially important diagnostic tool. Elderly patients represent a large and increasing group of emergency patients. Due to cognitive deficits, taking a reliable medical history in this patient group can be difficult. We sought to evaluate the medical history-taking in emergency patients above 75 years of age with respect to duration and completeness.Methods. Anonymous data of consecutive patients were recorded. Times for the defined basic medical history-taking were documented, as were the availability of other sources and times to assess these.Results. Data of 104 patients were included in the analysis. In a quarter of patients (25%,n=26) no complete basic medical history could be obtained. In the group of patients where complete data could be gathered, only 16 patients were able to provide all necessary information on their own. Including other sources like relatives or GPs prolonged the time until complete medical history from 7.3 minutes (patient only) to 26.4 (+relatives) and 56.3 (+GP) minutes.Conclusions. Medical histories are important diagnostic tools in the emergency setting and are prolonged in the elderly, especially if additional documentation and third parties need to be involved. New technologies like emergency medical cards might help to improve the availability of important patient data but implementation of these technologies is costly and faces data protection issues.
Teamwork Assessment Tools in Modern Surgical Practice: A Systematic Review
Authors: Whittaker George , Abboudi Hamid , Khan Muhammed Shamim , Dasgupta Prokar , Ahmed Kamran
Published: September 2015

Introduction. Deficiencies in teamwork skills have been shown to contribute to the occurrence of adverse events during surgery. Consequently, several teamwork assessment tools have been developed to evaluate trainee nontechnical performance. This paper aims to provide an overview of these instruments and review the validity of each tool. Furthermore, the present paper aims to review the deficiencies surrounding training and propose several recommendations to address these issues.Methods. A systematic literature search was conducted to identify teamwork assessment tools using MEDLINE (1946 to August 2015), EMBASE (1974 to August 2015), and PsycINFO (1806 to August 2015) databases.Results. Eight assessment tools which encompass aspects of teamwork were identified. The Nontechnical Skills for Surgeons (NOTSS) assessment was found to possess the highest level of validity from a variety of sources; reliability and acceptability have also been established for this tool.Conclusions. Deficits in current surgical training pathways have prompted several recommendations to meet the evolving requirements of surgeons. Recommendations from the current paper include integration of teamwork training and assessment into medical school curricula, standardised formal training of assessors to ensure accurate evaluation of nontechnical skill acquisition, and integration of concurrent technical and nontechnical skills training throughout training.
Growth Pattern of Clear Cell Renal Cell Carcinoma in Patients with Delayed Surgical Intervention: Fast Growth Rate Correlates with High Grade and May Result in Poor Prognosis
Authors: Zhang Lei , Yin Wenshi , Yao Lin , Li Xuesong , Fang Dong , Ren Da , Zhang Zhongyuan , Fan Yu , He Qun , Ci Weimin , He Zhisong , Zhou Liqun
Published: September 2015

Objectives.Previous studies revealed an unclear correlation between the growth rate of renal cell carcinoma (RCC) and tumor grade and did not focus on certain histological subtype. This report investigated the correlation between the growth rate and tumor grade in clear cell RCC (ccRCC).Methods. We reviewed 60 patients with 61 ccRCC confirmed by delayed surgeries after at least 12 months of active surveillance. The linear growth rate (LGR), volumetric growth rate (VGR), and volume doubling time (VDT) were calculated, and their correlations with clinicopathologic characteristics were analyzed.Results. The mean LGR, VGR, and VDT were 0.86 (range 0–4.74) cm/year, 20.96 (range 0.31–211.93) cm3/year, and 667 (range 33–3321) days, respectively. ccRCCs with high grade had greater LGR (P<0.001) and VGR (P=0.001) and lower VDT (P=0.017) than ccRCCs with low grade. Grade (OR = 5.185,P=0.004) was the only independent risk factor of LGR >0.5 cm/year, and grade (OR = 3.006,P=0.046) and initial size (OR = 0.392,P=0.004) were independent risk factors of VDT <1 year. Five patients developed metastasis after surgery with LGR >0.5 cm/yr altogether; of them, four had cancer-related death by the last follow-up.Conclusions. Fast growth rate of ccRCC is significantly correlated with high tumor grade and may result in poor prognosis, especially for those with LGR >0.5 cm/yr.
Do Panic Symptoms Affect the Quality of Life and Add to the Disability in Patients with Bronchial Asthma?
Authors: Faye A. D. , Gawande S. , Tadke R. , Kirpekar V. C. , Bhave S. H. , Pakhare A. P. , Tayade B.
Published: September 2015

Background. Anxiety and panic are known to be associated with bronchial asthma with variety of impact on clinical presentation, treatment outcome, comorbidities, quality of life, and functional disability in patients with asthma. This study aims to explore the pattern of panic symptoms, prevalence and severity of panic disorder (PD), quality of life, and disability in them.Methods. Sixty consecutive patients of bronchial asthma were interviewed using semistructured proforma, Panic and Agoraphobia scale, WHO Quality of life (QOL) BREF scale, and WHO disability schedule II (WHODAS II).Results. Though 60% of the participants had panic symptoms, only 46.7% had diagnosable panic attacks according to DSM IV TR diagnostic criteria and 33.3% had PD. Most common symptoms were “sensations of shortness of breath or smothering,” “feeling of choking,” and “fear of dying” found in 83.3% of the participants. 73.3% of the participants had poor quality of life which was most impaired in physical and environmental domains. 55% of the participants had disability score more than a mean (18.1).Conclusion. One-third of the participants had panic disorder with significant effect on physical and environmental domains of quality of life. Patients with more severe PD and bronchial asthma had more disability.
Impact of Interface Traps on Direct and Alternating Current in Tunneling Field-Effect Transistors
Authors: Jiang Zhi , Zhuang Yiqi , Li Cong , Wang Ping , Liu Yuqi
Published: September 2015

We demonstrate the impact of semiconductor/oxide interface traps (ITs) on the DC and AC characteristics of tunnel field-effect transistors (TFETs). Using the Sentaurus simulation tools, we show the impacts of trap density distribution and trap type on the n-type double gate- (DG-) TFET. The results show that the donor-type and acceptor-type ITs have the great influence on DC characteristic at midgap. Donor-like and acceptor-like ITs have different mechanism of the turn-on characteristics. The flat band shift changes obviously and differently in the AC analysis, which results in contrast of peak shift of Miller capacitorCgdfor n-type TFETs with donor-like and acceptor-like ITs.
Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental Autoimmune Encephalomyelitis in Transgenic Mice
Authors: Wright Tyler T , Jimenez Rachel V. , Morgan Todd E. , Bali Namrata , Hou Xiaogang , McCrory Mark A. , Finch Caleb E. , Szalai Alexander J.
Published: September 2015

We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is also expressed by both at low levels in the CNS. To determine if CNS expression of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific Ca2+/calmodulin-dependent protein kinase IIα(CaMKIIα) gene promoter. We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP, lessened EAE severity. These outcomes indicate that the protective actions of human CRP in EAE are manifested in the periphery and not in the CNS and reveal a previously unappreciated site specificity for the beneficial actions of CRP in CNS disease.
Genetic Interactions Explain Variance in Cingulate Amyloid Burden: An AV-45 PET Genome-Wide Association and Interaction Study in the ADNI Cohort
Authors: Li Jin , Zhang Qiushi , Chen Feng , Yan Jingwen , Kim Sungeun , Wang Lei , Feng Weixing , Saykin Andrew J. , Liang Hong , Shen Li
Published: September 2015

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Using discrete disease status as the phenotype and computing statistics at the single marker level may not be able to address the underlying biological interactions that contribute to disease mechanism and may contribute to the issue of “missing heritability.” We performed a genome-wide association study (GWAS) and a genome-wide interaction study (GWIS) of an amyloid imaging phenotype, using the data from Alzheimer’s Disease Neuroimaging Initiative. We investigated the genetic main effects and interaction effects on cingulate amyloid-beta (Aβ) load in an effort to better understand the genetic etiology of Aβdeposition that is a widely studied AD biomarker. PLINK was used in the single marker GWAS, and INTERSNP was used to perform the two-marker GWIS, focusing only on SNPs withp≤0.01for the GWAS analysis. Age, sex, and diagnosis were used as covariates in both analyses. Correctedpvalues using the Bonferroni method were reported. The GWAS analysis revealed significant hits within or proximal toAPOE,APOC1, andTOMM40genes, which were previously implicated in AD. The GWIS analysis yielded 8 novel SNP-SNP interaction findings that warrant replication and further investigation.
A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting
Authors: Hesketh Paul J. , Aapro Matti , Jordan Karin , Schwartzberg Lee , Bosnjak Snezana , Rugo Hope
Published: September 2015

Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV) related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1receptor antagonist (RA), netupitant, and the pharmacologically and clinically distinct 5-HT3RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.
Vibration and Stability of Variable Cross Section Thin-Walled Composite Shafts with Transverse Shear
Authors: Jing-min Ma , Yong-sheng Ren
Published: September 2015

A dynamic model of composite shaft with variable cross section is presented. Free vibration equations of the variable cross section thin-walled composite shaft considering the effect of shear deformation are established based on a refined variational asymptotic method and Hamilton’s principle. The numerical results calculated by Galerkin method are analyzed to indicate the effects of ply angle, taper ratio, and transverse shear deformation on the first natural frequency and critical rotating speed. The results are compared with those obtained by using finite element package ANSYS and available in the literature using other models.
Reduced-Pressure Boiling Extraction of Oleuropein Coupled with Ultrasonication from Olive Leaves (Olea europaeaL.)
Authors: Xie Pu-jun , Huang Li-xin , Zhang Cai-hong , You Feng , Wang Cheng-zhang , Zhou Hao
Published: September 2015

Oleuropein was extracted fromFrantoioolive leaves using reduced-pressure boiling extraction coupled with ultrasound-assist (URPE). Four important factors, extraction temperature, ultrasonic power, ethanol concentration, and the ratio of solid to liquid, were selected to carry out the response surface methodology (RSM) for seeking optimal conditions on high oleuropein extraction yield at different levels. Box-Behnken design was employed to investigate the effects of the four factors on it. The results showed that the ratio of solid to liquid was the most significant factor of all on oleuropein yield. The optimal operation conditions were obtained as follows: ethanol concentration 75% (v/v), extraction temperature 53°C, ultrasonic power 600 W, and the ratio of solid to liquid 1 : 31. Under these optimal conditions, oleuropein extraction yield was 7.08%, which was close to the predicted value 7.121%. The scanning electron microscope (SEM) images of olive leaves after extraction were provided as well. It was seen that, compared with the untreated leaves, URPE could effectively break cells within the olive leaves.
Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma
Authors: Ambrosio Maria R. , Rocca Bruno J. , Barone Aurora , Onorati Monica , Mundo Lucia , Crivelli Filippo , Di Nuovo Franca , De Falco Giulia , del Vecchio Maria T. , Tripodi Sergio A. , Tosi Piero
Published: September 2015

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functionalin vitroandin vivostudies are needed to verify this hypothesis.
Retrospective Clinical and Radiological Outcomes after Robotic Assisted Bicompartmental Knee Arthroplasty
Authors: Tamam Cuneyt , Plate Johannes F. , Augart Marco , Poehling Gary G. , Jinnah Riyaz H.
Published: September 2015

Purpose. Bicompartmental knee arthroplasty (BiKA) is a favorable alternative to total knee arthroplasty for degenerative disease limited to two knee compartments. Recently developed robotic-assisted systems improved the clinical efficacy of unicompartmental knee arthroplasty by providing enhanced component positioning with dynamic ligament balancing. The purpose of this study was to evaluate the short-term outcomes of patients, undergoing bicompartmental knee arthroplasty at a single institution by a single surgeon using a robotic-assisted system. It was hypothesized that robotic assisted BiKA is a prevailing choice for degenerative disease limited to two knee compartments with good functional results.Methods. A search of the institution’s joint registry was conducted to identify patients that underwent robotic-assisted BiKA of the patellofemoral compartment and the medial or lateral compartment.Results. A total number of 29 patients (30 BiKA) with a mean age of 63.6 years were identified who received a patellofemoral resurfacing in combination with medial or lateral compartment resurfacing. Twenty-four out of 29 patients had good to excellent outcome.Conclusion. Robotic assisted bicompartmental arthroplasty using broad indications and only excluding patients with severe deformity and those that have less than 4 mm of joint space in the surviving compartment demonstrated 83% good to excellent results.
Understanding Transcription Factor Regulation by Integrating Gene Expression and DNase I Hypersensitive Sites
Authors: Wang Guohua , Wang Fang , Huang Qian , Li Yu , Liu Yunlong , Wang Yadong
Published: September 2015

Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5–20 bp long) specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours), we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.
Validation of a RP-HPLC-DAD Method for Chamomile (Matricaria recutita) Preparations and Assessment of the Marker, Apigenin-7-glucoside, Safety and Anti-Inflammatory Effect
Authors: Miguel Felipe Galeti , Cavalheiro Amanda Henriques , Spinola Nathália Favaretto , Ribeiro Diego Luis , Barcelos Gustavo Rafael Mazzaron , Antunes Lusânia Maria Greggi , Hori Juliana Issa , Marquele-Oliveira Franciane , Rocha Bruno Alves , Berretta Andresa Aparecida
Published: September 2015

Chamomile is a medicinal plant, which presents several biological effects, especially the anti-inflammatory effect. One of the compounds related to this effect is apigenin, a flavonoid that is mostly found in its glycosylated form, apigenin-7-glucoside (APG), in natural sources. However, the affectivity and safety of this glycoside have not been well explored for topical application. In this context, the aim of this work was to develop and validate a reversed-phase high-performance liquid chromatography (RP-HPLC-DAD) method to quantify APG in chamomile preparations. Additionally, the safety and the anti-inflammatory potential of this flavonoid were verified. The RP-HPLC-DAD method was developed and validated with linearity at 24.0–36.0 μg/mL range (r=0.9994). Intra- and interday precision (RSD) were 0.27–2.66% and accuracy was 98.27–101.21%. The validated method was applied in the analysis of chamomile flower heads, glycolic extract, and Kamillen cream, supporting the method application in the quality control of chamomile preparations. Furthermore, the APG safety was assessed by MTT cytotoxicity assay and mutagenic protocols and the anti-inflammatory activity was confirmed by a diminished TNF-αproduction showed by mice macrophages treated with APG following LPS treatment.
MicroRNA Promoter Identification inArabidopsisUsing Multiple Histone Markers
Authors: Zhao Yuming , Wang Fang , Juan Liran
Published: September 2015

A microRNA is a small noncoding RNA molecule, which functions in RNA silencing and posttranscriptional regulation of gene expression. To understand the mechanism of the activation of microRNA genes, the location of promoter regions driving their expression is required to be annotated precisely. Only a fraction of microRNA genes have confirmed transcription start sites (TSSs), which hinders our understanding of the transcription factor binding events. With the development of the next generation sequencing technology, the chromatin states can be inferred precisely by virtue of a combination of specific histone modifications. Using the genome-wide profiles of nine histone markers including H3K4me2, H3K4me3, H3K9Ac, H3K9me2, H3K18Ac, H3K27me1, H3K27me3, H3K36me2, and H3K36me3, we developed a computational strategy to identify the promoter regions of most microRNA genes inArabidopsis, based upon the assumption that the distribution of histone markers around the TSSs of microRNA genes is similar to the TSSs of protein coding genes. Among 298 miRNA genes, our model identified 42 independent miRNA TSSs and 132 miRNA TSSs, which are located in the promoters of upstream genes. The identification of promoters will provide better understanding of microRNA regulation and can play an important role in the study of diseases at genetic level.
Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors
Authors: Vlassenko Andrei G. , McConathy Jonathan , Couture Lars E. , Su Yi , Massoumzadeh Parinaz , Leeds Hayden S. , Chicoine Michael R. , Tran David D. , Huang Jiayi , Dahiya Sonika , Marcus Daniel S. , Fouke Sarah Jost , Rich Keith M. , Raichle Marcus E. , Benzinger Tammie L. S.
Published: September 2015

Objectives.Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG), is a hallmark of active cancer cells that is not directly measured with standard18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism.Methods.Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF), oxygen (CMRO2) and glucose (CMRGlu) metabolism, and AG, using15O-labeled CO, O2and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals.Results.Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures.Conclusions.Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.
Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study
Authors: Matrat Mireille , Guida Florence , Cénée Sylvie , Févotte Joelle , Carton Matthieu , Cyr Diane , Menvielle Gwenn , Paget-Bailly Sophie , Radoï Loredana , Schmaus Annie , Bara Simona , Velten Michel , Luce Danièle , Stücker Isabelle , The Icare Study Group
Published: September 2015

Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure.Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM.Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos.Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent.
Preoperative Neutrophil-to-Lymphocyte Ratio and Neutrophilia Are Independent Predictors of Recurrence in Patients with Localized Papillary Renal Cell Carcinoma
Authors: Huang Jiwei , Dahl Douglas M. , Dong Liang , Liu Qiang , Cornejo Kristine , Wang Qi , Wu Shulin , Feldman Adam S. , Huang Yiran , Xue Wei , Wu Chin-Lee
Published: September 2015

Objective. To evaluate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) in patients’ prognosis with localized papillary renal cell carcinoma (pRCC).Methods. Data from 218 localized pRCC patients (T1-3 N0/+ M0), operated between 1991 and 2011 at two centers, were evaluated retrospectively. Univariable and multivariable analyses using the Cox regression model were performed to determine the associations of NLR and ANC with recurrence-free survival (RFS). Prognostic accuracy was evaluated with the Harrell concordance index.Results. The 5-year RFS rate was 87.0%. Multivariable analysis identified increased NLR (≥3.6) and ANC (≥5300/μL) as independent prognostic factors for RFS (hazard ratio (HR) = 4.01,P=0.018) and (HR = 4.71,P=0.045). The final model built by the addition of NLR or ANC improved predictive accuracy (c-index: 0.824, 0.842) compared with the clinicopathological base model (c-index: 0.800), which included TNM stage and tumor necrosis.Conclusions. The NLR and ANC appear to be independent prognostic factors for RFS after surgery for localized pRCC. They significantly increase the accuracy of established prognostic factors. Therefore, we recommend adding NLR and ANC to traditional prognostic model, which may improve its predictive accuracy.
Prophylactic Management of Radiation-Induced Nausea and Vomiting
Authors: Feyer Petra , Jahn Franziska , Jordan Karin
Published: September 2015

The incidence of nausea and vomiting after radiotherapy is often underestimated by physicians, though some 50–80% of patients may experience these symptoms. The occurrence of radiotherapy-induced nausea and vomiting (RINV) will depend on radiotherapy-related factors, such as the site of irradiation, the dosing, fractionation, irradiated volume, and radiotherapy techniques. Patients should receive antiemetic prophylaxis as suggested by the international antiemetic guidelines based upon a risk assessment, taking especially into account the affected anatomic region and the planned radiotherapy regimen. In this field the international guidelines from the Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) guidelines as well as the National Comprehensive Cancer Network (NCCN) are widely endorsed. The emetogenicity of radiotherapy regimens and recommendations for the appropriate use of antiemetics including 5-hydroxytryptamine (5-HT3) receptor antagonists, steroids, and other antiemetics will be reviewed in regard to the applied radiotherapy or radiochemotherapy regimen.
Low-Cost Biodegradation and Detoxification of Textile Azo Dye C.I. Reactive Blue 172 byProvidencia rettgeriStrain HSL1
Authors: Lade Harshad , Govindwar Sanjay , Paul Diby
Published: September 2015

Present study focuses on exploitation of agricultural waste wheat bran (WB) as growth medium for degradation of textile azo dye C.I. Reactive Blue 172 (RB 172) using a single bacteriumP. rettgeristrain HSL1 (GenBank accession numberJX853768.1). The bacterium was found to completely decolorize 50 mg L−1of dye RB 172 within 20 h at 30 ± 0.2°C under microaerophilic incubation conditions. Additionally, significant reduction in COD (85%) and TOC (52%) contents of dye decolorized medium was observed which suggested its mineralization. Induction in the activities of azoreductase (159%) and NADH-DCIP reductase (88%) provided an evidence for reductive cleavage of dye RB 172. The HPLC, FTIR, and GC-MS analysis of decolorized products confirmed the degradation of dye into various metabolites. The proposed metabolic pathway for biodegradation of RB 172 has been elucidated which showed the formation of 2 intermediate metabolites, namely, 4-(ethenylsulfonyl) aniline and 1-amino-1-(4-aminophenyl) propan-2-one. The acute and phytotoxicity evaluation of degraded metabolites suggests that bacterial strain favors the detoxification of dye RB 172. Thus, WB could be utilized as a low-cost growth medium for the enrichment of bacteria and their further use for biodegradation of azo dyes and its derivatives containing wastes into nontoxic form.
Fatal Epstein-Barr Virus Reactivation in an Acquired Aplastic Anemia Patient Treated with Rabbit Antithymocyte Globulin and Cyclosporine A
Authors: Takahashi Tohru , Maruyama Yumiko , Saitoh Mayuko , Itoh Hideto , Yoshimoto Mitsuru , Tsujisaki Masayuki
Published: September 2015

Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after immunosuppressive therapy for aplastic anemia (AA) is extremely rare in a nontransplant setting and has not been well described. This report describes a severe AA patient in whom fatal EBV-LPD developed after being treated with rabbit antithymocyte globulins (ATG) and cyclosporine A (CsA). An 81-year-old man was diagnosed as having severe AA. He was started on CsA followed by administration of ATG for five consecutive days. One month after the start of ATG, persistent fever which was not responsive to antibiotics or antifungal agents developed and atypical lymphocytes emerged in peripheral blood. Repeated blood cultures were negative. An extremely high level of EBV virus in his peripheral blood plasma was detected by means of a quantitative real-time PCR assay. Even after the cessation of CsA, the fever persisted and the peripheral atypical lymphocytes proliferated rapidly. The patient suffered from respiratory failure, liver dysfunction, and metabolic acidosis. Rituximab was administered without success and he died.
A Derivative-Free Conjugate Gradient Method and Its Global Convergence for Solving Symmetric Nonlinear Equations
Authors: Waziri Mohammed Yusuf , Sabi’u Jamilu
Published: September 2015

We suggest a conjugate gradient (CG) method for solving symmetric systems of nonlinear equations without computing Jacobian and gradient via the special structure of the underlying function. This derivative-free feature of the proposed method gives it advantage to solve relatively large-scale problems (500,000 variables) with lower storage requirement compared to some existing methods. Under appropriate conditions, the global convergence of our method is reported. Numerical results on some benchmark test problems show that the proposed method is practically effective.
Targeting Ribonucleotide Reductase M2 and NF-κB Activation with Didox to Circumvent Tamoxifen Resistance in Breast Cancer
Authors: Shah Khyati N. , Wilson Elizabeth A. , Malla Ritu , Elford Howard L. , Faridi Jesika S.
Published: September 2015

Tamoxifen is widely used as an adjuvant therapy for patients with estrogen receptor (ERα)–positive tumors. However, the clinical benefit is often limited because of the emergence of drug resistance. In this study, overexpression of ribonucleotide reductase M2 (RRM2) in MCF-7 breast cancer cells resulted in a reduction in the effectiveness of tamoxifen, through downregulation of ERα66 and upregulation of the 36-kDa variant of ER (ERα36). We identified that NF-κB, HIF1α, and MAPK/JNK are the major pathways that are affected by RRM2 overexpression and result in increased NF-κB activity and increased protein levels of EGFR, HER2, IKKs, Bcl-2, RelB, and p50. RRM2-overexpressing cells also exhibited higher migratory and invasive properties. Through time-lapse microscopy and protein profiling studies of tamoxifen-treated MCF-7 and T-47D cells, we have identified that RRM2, along with other key proteins, is altered during the emergence of acquired tamoxifen resistance. Inhibition of RRM2 using siRRM2 or the ribonucleotide reductase (RR) inhibitor didox not only eradicated and effectively prevented the emergence of tamoxifen-resistant populations but also led to the reversal of many of the proteins altered during the process of acquired tamoxifen resistance. Because didox also appears to be a potent inhibitor of NF-κB activation, combining didox with tamoxifen treatment cooperatively reverses ER-α alterations and inhibits NF-κB activation. Finally, inhibition of RRM2 by didox reversed tamoxifen-resistant in vivo tumor growth and decreased in vitro migratory and invasive properties, revealing a beneficial effect of combination therapy that includes RRM2 inhibition to delay or abrogate tamoxifen resistance. Mol Cancer Ther; 14(11); 2411–21. ©2015 AACR.
Radiotherapy of the Lymphatic Pathways in Early Breast Cancer
Authors: Sautter-Bihl Marie-Luise , Sedlmayer Felix
Published: September 2015

International guidelines reveal substantial differences regarding indications for regional nodal irradiation (RNI). Recently, several randomized studies provided new insights and these are discussed here. Patients with 1-3 positive nodes seem to profit from RNI compared to whole-breast (WBI) or chest-wall irradiation (CWI) alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and 1 meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel nodes or microscopic metastases on prognosis are equivocal. Recent data suggest that the current restrictive use of RNI should be scrutinized, as the hazard-benefit relation appears to shift towards an improvement of outcome.
Current Treatment of Isolated Locoregional Breast Cancer Recurrences
Authors: Harms Wolfgang , Geretschläger Andreas , Cescato Corinne , Buess Martin , Köberle Dieter , Asadpour Branca
Published: September 2015

Patients with isolated locoregional breast cancer recurrences should be treated with curative intent. Mastectomy is regarded as the standard of care for patients with ipsilateral breast tumor recurrence. In a selected group of patients, partial breast irradiation after second breast-conserving surgery is a viable alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory, especially in patients who had not been irradiated previously. In case of re-irradiation, the largest experience exists for multi-catheter brachytherapy. Prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. In patients with resectable locoregional breast cancer recurrences after mastectomy, multi-modal therapy comprising complete resection, radiation therapy in previously unirradiated patients, and systemic therapy results in 5-year disease-free and overall survival rates of 69% and 88%, respectively. In radiation-naive patients with unresectable, isolated locoregional recurrences, radiation therapy is mandatory. In selected patients with previous irradiations and unresectable locoregional recurrences, a second irradiation as part of an individual treatment concept can be applied. The increased risk of severe toxicity should always be weighed up against the potential clinical benefit. A combination therapy with hyperthermia can further improve the treatment results.
Platelet microparticles reprogram macrophage gene expression and function
Authors: Rousseau Matthieu , Duchez Anne-Claire , Lee Chan Ho C. , Boilard Eric , Laffont Benoit , Corduan Aurélie , Provost Patrick
Published: September 2015

Platelet microparticles (MPs) represent the most abundant MPs subtype in the circulation, and can mediate intercellular communication through delivery of bioactives molecules, such as cytokines, proteins, lipids and RNAs. Here, we show that platelet MPs can be internalised by primary human macrophages and deliver functional miR-126–3p. The increase in macrophage miR-126–3p levels was not prevented by actinomycin D, suggesting that it was not due to de novo gene transcription. Platelet MPs dose-dependently downregulated expression of four predicted mRNA targets of miR-126–3p, two of which were confirmed also at the protein level. The mRNA downregulatory effects of platelet MPs were abrogated by expression of a neutralising miR-126–3p sponge, implying the involvement of miR-126–3p. Transcriptome-wide, microarray analyses revealed that as many as 66 microRNAs and 653 additional RNAs were significantly and differentially expressed in macrophages upon exposure to platelet MPs. More specifically, platelet MPs induced an upregulation of 34 microRNAs and a concomitant downregulation of 367 RNAs, including mRNAs encoding for cytokines/chemokines CCL4, CSF1 and TNF. These changes were associated with reduced CCL4, CSF1 and TNF cytokine/chemokine release by macrophages, and accompanied by a marked increase in their phagocytic capacity. These findings demonstrate that platelet MPs can modify the transcriptome of macrophages, and reprogram their function towards a phagocytic phenotype.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Percepciones en salud bucal de los niños y niñas
Authors: GonzáLez-penagos Catalina , Cano-Gómez Melissa , Meneses-Gómez Edwin j. , Vivares-builes Annie M.
Published: September 2015

(analítico): Identificamos las necesidades de salud bucal de los niños y niñas de 2 a 5 años del programa Buen Comienzo-Fantasías de las Américas, desde la percepción de las agentes educativas en la ciudad de Medellín, en el año 2013. Realizamos un estudio cualitativo, con enfoque histórico hermenéutico; la población de estudio correspondió a 65 agentes educativas. Los resultados preliminares reflejan necesidades relacionadas con el acceso y oportunidad de atención odontológica, la deficiencia en las acciones de promoción de la salud y prevención de las enfermedades prevalentes en salud bucal, el desconocimiento y la falta de motivación de los hábitos de higiene bucal, su importancia en la prevención de las patologías bucales y su implicación con el crecimiento y desarrollo, y con la salud general de los menores y las menores.