bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Clinical Research of Jejunal Interposition in Adenocarcinoma of the Esophagogastric Junction II/III Proximal Gastrectomy
Authors: Tao Kai , Dong Jian-Hong
Published: October 2016

Objective.To investigate the feasibility and specific methods of single-tract jejunal interposition between esophagus and remnant stomach (ers-STJI) in adenocarcinoma of the esophagogastric junction (AEG) II/III proximal gastrectomy.Methods.15 AEG II/III gastric cancer (GC) patients in phase T1-3N0M0 with tumor size <5 cm were selected and they underwent proximal gastrectomy with ers-STJI from August 2013 to August 2014.Results.All of the 15 patients successfully completed GC R0 proximal gastrectomy with ers-STJI and no operative death or no significant complication occurred; one patient had anastomotic inflammatory granuloma. The digestive tract reconstruction time was 29.5 ± 5.7 min; the intraoperative blood loss was 96.7 ± 20.2 mL, and the number of lymph node dissections was 21.3 ± 3.0; the postoperative flatus time was 48.2 ± 11.9 h; the average length of hospital stay was 10.7 ± 2.3 d, and the average hospital stay cost was 60 ± 3 thousands. All of the patients were followed up for 12 months, and their postoperative single food intake, body weight, hemoglobin, and albumin were all recovered to the preoperative levels.Conclusions.The applications of ers-STJI in proximal gastrectomy were safe and feasible, and the length of jejunal interposition could be 15–25 cm.
An Investigation of the Levels and Distribution of Selected Heavy Metals in Sediments and Plant Species within the Vicinity of Ex-Iron Mine in Bukit Besi
Authors: Kutty Ahmad A. , Al-Mahaqeri Sarah A.
Published: October 2016

An assessment of the abandoned mine impacts on the concentrations and distribution of heavy metals in surface sediments and plant species within the vicinity of an ex-iron mine in Malaysia was conducted. The sequential extraction method was used to extract anthropogenic metals in sediments. The results showed that metals in EFLE, AR, and OO fractions were higher than ambient concentrations which indicate that heavy metals have been loaded from ex-iron mining area into the surrounding aquatic environments. The metal accumulation in the four dominant plant species grown naturally within the vicinity of Bukit Besi ex-iron mining was investigated. Exceptional elevated concentrations of metal were found in plants and surface sediments. Several established criteria were applied to determine the hyperaccumulator plants. The results revealed thatMelastoma malabathricumandPityrogramma calomelanosare classified as Fe and Al hyperaccumulators, whileScirpus triqueter,Melastoma malabathricum, andPityrogramma calomelanoswere undoubtedly hyperaccumulator for Cd.
Salient Region Detection by Fusing Foreground and Background Cues Extracted from Single Image
Authors: Zhou Qiangqiang , Zhao Weidong , Zhang Lin , Wang Zhicheng
Published: October 2016

Saliency detection is an important preprocessing step in many application fields such as computer vision, robotics, and graphics to reduce computational cost by focusing on significant positions and neglecting the nonsignificant in the scene. Different from most previous methods which mainly utilize the contrast of low-level features, various feature maps are fused in a simple linear weighting form. In this paper, we propose a novel salient object detection algorithm which takes both background and foreground cues into consideration and integrate a bottom-up coarse salient regions extraction and a top-down background measure via boundary labels propagation into a unified optimization framework to acquire a refined saliency detection result. Wherein the coarse saliency map is also fused by three components, the first is local contrast map which is in more accordance with the psychological law, the second is global frequency prior map, and the third is global color distribution map. During the formation of background map, first we construct an affinity matrix and select some nodes which lie on border as labels to represent the background and then carry out a propagation to generate the regional background map. The evaluation of the proposed model has been implemented on four datasets. As demonstrated in the experiments, our proposed method outperforms most existing saliency detection models with a robust performance.
Synthesis and Assessment of Antibacterial Activities of Ruthenium(III) Mixed Ligand Complexes Containing 1,10-Phenanthroline and Guanide
Authors: Abebe Atakilt , Hailemariam Tizazu
Published: October 2016

In this work, two complexes of ruthenium(III) ([Ru(phen)2Cl2]Cl·2H2O and [Ru(phen)2(G)Cl]2Cl·H2O) were synthesized from 1,10-phenanthroline alone as well as from both 1,10-phenanthroline and guanide. The synthesis was checked using halide test, conductance measurement, and spectroscopic (ICP-OES, FTIR, and UV/Vis) analysis. Their in vitro antibacterial activities were also investigated on two Gram-positive (Staphylococcus aureus (S. aureus) and methicillin resistant Staphylococcus aureus (MRSA)) and two Gram-negative (Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae)) bacteria. These complexes showed wide-range better activities than the commercially available controls (Chloramphenicol and Ciprofloxacin) against even the most drug resistant K. pneumoniae. [Ru(phen)2(G)Cl]2Cl·H2O inhibited S. aureus, MRSA, E. coli, and K. pneumoniae by 17.5%, 27.4%, 16%, and 52%, respectively, better than Chloramphenicol. It also inhibited these pathogens by 5.9%, 5.1%, 2.3%, and 17.2%, respectively, better than Ciprofloxacin. Similarly, [Ru(Phen)2(Cl)2]Cl·2H2O inhibited these pathogens by 11%, 8.7%, 0.1%, and 31.2%, respectively, better than Chloramphenicol. Therefore, after in vivo cytotoxicity investigations, these compounds can be considered as potential antibiotic drugs.
Instrumental and Sensory Analysis of the Properties of Traditional Chinese Fried Fritters
Authors: Fan Daming , Yan Bowen , Lian Huizhang , Zhao Jianxin , Zhang Hao
Published: October 2016

The quality of traditional Chinese fried fritters is typically measured using human sensory evaluation techniques and physicochemical indices, the process of which is laborious and time-consuming. This study aimed to investigate the relationship between instrumental parameters, sensory criteria, and physicochemical indices. Significant correlations were found using principle component analysis. Volume, fat, texture, palatability, and instrumental parameters (hardness, fracturability, springiness, and gumminess) were found to be the main factors influencing the quality of Chinese fried fritters by principal component analysis (PCA) and instrumental methods, which were satisfactory replacement for human evaluation in correlation testing.
Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability
Authors: Chávez-Galán Leslie , Vesin Dominique , Martinvalet Denis , Garcia Irene
Published: October 2016

Mycobacterium bovisBCG, the current vaccine against tuberculosis, is ingested by macrophages promoting the development of effector functions including cell death and microbicidal mechanisms. Despite accumulating reports onM. tuberculosis, mechanisms of BCG/macrophage interaction remain relatively undefined. In vivo, few bacilli are sufficient to establish a mycobacterial infection; however, in vitro studies systematically use high mycobacterium doses. In this study, we analyze macrophage/BCG interactions and microenvironment upon infection with low BCG doses and propose an in vitro model to study cell activation without affecting viability. We show that RAW macrophages infected with BCG at MOI 1 activated higher and sustained levels of proinflammatory cytokines and transcription factors while MOI 0.1 was more efficient for early stimulation of IL-1β, MCP-1, and KC. Both BCG infection doses induced iNOS and NO in a dose-dependent manner and maintained nuclear and mitochondrial structures. Microenvironment generated by MOI 1 induced macrophage proliferation but not MOI 0.1 infection. In conclusion, BCG infection at low dose is an efficient in vitro model to study macrophage/BCG interactions that maintains macrophage viability and mitochondrial structures. This represents a novel model that can be applied to BCG research fields including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies.
The Influence of the Variety, Vineyard, and Vintage on the Romanian White Wines Quality
Authors: Hosu Anamaria , Floare-Avram Veronica , Magdas Dana Alina , Feher Ioana , Inceu Mihai , Cimpoiu Claudia
Published: October 2016

The wine is one of the most consumed drinks over the world, being subjected to falsification or adulteration regarding the variety, vintage, and geographical region. In this study, the influence of different characteristics of wines (type, production year, and origin) on the total phenolic content, total flavonoids content, antioxidant activity, total sugars content, pH, and18O/16O isotopic ratio was investigated. The differentiation of selected wines on the basis of tested parameters was investigated using chemometric techniques, such as analysis of variance, cluster analysis, and principal component analysis. The experimental results are in agreement with other outcomes and allow concluding that variety and vineyard have the major influence on the studied parameters, but, also, statistical interaction effect between year and vineyard and year and variety is observed in some cases. The obtained results have demonstrated that these parameters together with chemometric techniques show a significant potential to be used for discrimination of white wines.
A Photochromic Copolymer Hydrogel Contact Lens: From Synthesis to Application
Authors: Yang Xiaoli , Huang Limin , Zhou Lihua , Xu Hao , Yi Zihan
Published: October 2016

A photochromic poly(2-hydroxyl-ethyl methacrylate-N-vinylpyrrolidone-spironaphthoxazine) hydrogel (p(HEMA-NVP-SPO)) has been designed and synthesized by free radical polymerization in this work. The chemical and structural information of hydrogels was investigated by IR spectra, equilibrium water content (EWC), and SEM. The IR spectra confirmed successful synthesis of copolymer. The domain of NVP contributed to not only EWC but also inner structure of hydrogel, while SPO had little influence on these properties of hydrogel. The photochromic behaviors of hydrogel including photochromic properties and thermal fading kinetics were systematically studied and compared with hydrogel made by immersing method. Results showed that when SPO was incorporated in hydrogel by polymerization, maximum absorbance wavelength got shorter, and the relaxation half-life became longer. In addition, salicylic acid as a drug model could be loaded into hydrogel by immersing method, and its sustained drug release in a given period was dependent on the characteristics of solution and loading time.
Lay Health Trainers Supporting Self-Management amongst Those with Low Heath Literacy and Diabetes: Lessons from a Mixed Methods Pilot, Feasibility Study
Authors: Bartlam Bernadette , Rathod Trishna , Rowlands Gillian , Protheroe Joanne
Published: October 2016

This article reports a mixed methods process evaluation of a pilot feasibility randomised controlled trial comparing a Lay Health Trainer (LHT) intervention and usual care for those with poorly controlled Type 2 Diabetes Melitus (T2DM). Set in a deprived area in the UK, this research explores patient and health care practitioner (HCP) views on whether a structured interview between a patient and a Lay Health Trainer (LHT), for the purpose of developing a tailored self-management plan for patients, is acceptable and likely to change health behaviours. In doing so, it considers the implications for a future, randomised controlled trial (RCT). Participants were patients, LHTs delivering the intervention, service managers, and practice nurses recruiting patients to the study. Patients were purposively sampled on their responses to a baseline survey, and semistructured interviews were conducted within an exploratory thematic analysis framework. Findings indicate that the intervention is acceptable to patients and HCPs. However, LHTs found it challenging to work with older patients with long-term and/or complex conditions. In order to address this, given an ageing population and concomitant increases in those with such health needs, LHT training should develop skills working with these populations. The design of any future RCT intervention should take account of this.
Stroke from Vasospasm due to Marijuana Use: Can Cannabis Synergistically with Other Medications Trigger Cerebral Vasospasm?
Authors: Jamil Marium , Zafar Atif , Adeel Faizi Syed , Zawar Ifrah
Published: October 2016

We present a case of imaging proven cerebral vasospasm causing ischemic stroke in a young patient chronically on buprenorphine-naloxone for heroin remission who started smoking cannabis on a daily basis. With cannabis legalization spreading across the states in the USA, it is important for physicians not only to be aware of cannabis reported association with cerebral vasospasm in some patients but also to be on the lookout for possible interacting medications that can synergistically affect cerebral vessels causing debilitating strokes.
Plasma Exchange in the Management of Catastrophic Antiphospholipid Syndrome
Authors: Titeca-Beauport Dimitri , Salle Valery , Kontar Loay , Maizel Julien , Choukroun Gabriel
Published: October 2016

Objective. Report of a case of catastrophic antiphospholipid syndrome (CAPS) with multiple organ involvement leading to a life-threatening condition despite early combination corticosteroid and heparin therapy. Initiation of plasma exchange led to rapid improvement of the patient’s general condition. Design. Case report. Setting. University teaching hospital medical intensive care unit. Patient. Single case: 52-year-old man hospitalized for catastrophic antiphospholipid syndrome (CAPS) with cardiac, renal, and cutaneous involvement. Despite early methylprednisolone and heparin therapy, the patient’s condition progressively deteriorated, resulting in acute renal failure, right adrenal hemorrhage, and pulmonary involvement, leading to acute respiratory distress on day 6, requiring high-flow nasal cannula oxygen therapy with FiO2 of 1.0. Interventions. Plasma exchange was started on day 6. Endpoints and Main Results. A marked improvement of the patient’s general condition was observed after initiation of plasma exchange, with successful weaning of oxygen therapy and normalization of platelet count, troponin, and serum creatinine within four days. Conclusions. This case illustrates the efficacy of plasma exchange in CAPS and the difficulty for physicians to determine the optimal timing of plasma exchange.
Approximating the Solution Stochastic Process of the Random Cauchy One-Dimensional Heat Model
Authors: Navarro-Quiles A. , Romero J.-V. , Roselló M.-D. , Sohaly M. A.
Published: October 2016

This paper deals with the numerical solution of the random Cauchy one-dimensional heat model. We propose a random finite difference numerical scheme to construct numerical approximations to the solution stochastic process. We establish sufficient conditions in order to guarantee the consistency and stability of the proposed random numerical scheme. The theoretical results are illustrated by means of an example where reliable approximations of the mean and standard deviation to the solution stochastic process are given.
Randomized Clinical Trial of Composite Restorations in Primary Teeth: Effect of Adhesive System after Three Years
Authors: Donmez Secil Bektaş , Turgut Melek D. , Uysal Serdar , Ozdemir Pinar , Tekcicek Meryem , Zimmerli Brigitte , Lussi Adrian
Published: October 2016

The purpose of this study was to assess the clinical performance of composite restorations placed with different adhesive systems in primary teeth. In 32 patients, 128 composite restorations were placed using a split-mouth design as follows (4 groups/patient): three-step etch-and-rinse (Group 1), two-step etch-and-rinse (Group 2), two-step self-etch (Group 3), and one-step self-etch (Group 4). The restorations were clinically evaluated at baseline and at 6, 18, and 36 months according to the FDI criteria. There was no significant difference between the adhesive systems in retention of the restorations (p>0.05). Over time, there was a statistically significant decrease in marginal adaptation in all groups, whereas surface and marginal staining significantly increased in Groups 3 and 4 (p<0.05). The etch-and-rinse adhesive systems resulted in better marginal adaptation than the self-etch adhesive systems (p<0.05). It was concluded that preetching of the primary enamel might help improve the clinical performance of the self-etch adhesive systems in primary teeth.
Diet, Lifestyles, Family History, and Prostate Cancer Incidence in an East Algerian Patient Group
Authors: Lassed Somia , Deus Cláudia M. , Lourenço Nuno , Dahdouh Abderrezak , Rizvanov Albert A. , Oliveira Paulo J. , Zama Djamila
Published: October 2016

Prostate cancer (PC) is the fourth most common cancer in men and the sixth leading cause of death in Algeria. To examine the relationship between lifestyle factors, including diet, and family history and PC risk, a case-control study was performed in an eastern Algerian population, comprising 90 patients with histologically confirmed PC and 190 controls. Data collection was carried out through a structured questionnaire and statistical analysis was performed to evaluate the different variables. The data showed that consumption of lamb and beef meat and high intake of animal fat and dairy products increased PC risk. Seven to thirteen vegetables servings per week and fourteen or more servings decreased PC risk by 62% and 96%, respectively. Seven to fourteen fruit servings per week decrease PC risk by 98%. Green tea consumption reduced the risk of PC but the results were statistically borderline. Increased risk was observed for individuals with family history of PC in first and in second degree. A positive strong association was also found for alcohol and smoking intake and a dose-response relationship existed for quantity and history of smoking. This study suggests that dietary habits, lifestyle factors, and family history have influence on the development of PC in Algerian population.
The Impact of Walking Exercises and Resistance Training upon the Walking Distance in Patients with Chronic Lower Limb Ischaemia
Authors: Szymczak Maria , Oszkinis Grzegorz , Majchrzycki Marian
Published: October 2016

Objective. The objective of this paper is to compare the impact of supervised walking and resistance training upon the walking distance in PAD patients. Materials and Methods. The examination involved 50 PAD patients at the 2nd stage of the disease according to Fontaine’s scale. The participants were randomly allocated to two groups: one exercising on the treadmill (n=24) and one performing resistance exercises of lower limbs (n=26). Results. The 12-week program of supervised rehabilitation led to a significant increase in the intermittent claudication distance measured both on the treadmill and during the 6-minute walking test. The group training on the treadmill showed a statistically significant increase of the initial claudication distance (ICD) and the absolute claudication distance (ACD) measured on the treadmill, as well as of ICD and the total walking distance (TWD) measured during the 6-minute walking test. Within the group performing resistance exercises, a statistically significant improvement was observed in the case of parameters measured on the treadmill: ICD and ACD. Conclusions. The supervised rehabilitation program, in the form of both walking and resistance exercises, contributes to the increase in the intermittent claudication distance. The results obtained in both groups were similar.
Brilliant Blue Dyes in Daily Food: How Could Purinergic System Be Affected?
Authors: Ferreira Leonardo Gomes Braga , Faria Robson Xavier , Ferreira Natiele Carla da Silva , Soares-Bezerra Rômulo José
Published: October 2016

Dyes were first obtained from the extraction of plant sources in the Neolithic period to produce dyed clothes. At the beginning of the 19th century, synthetic dyes were produced to color clothes on a large scale. Other applications for synthetic dyes include the pharmaceutical and food industries, which are important interference factors in our lives and health. Herein, we analyzed the possible implications of some dyes that are already described as antagonists of purinergic receptors, including special Brilliant Blue G and its derivative FD&C Blue No. 1. Purinergic receptor family is widely expressed in the body and is critical to relate to much cellular homeostasis maintenance as well as inflammation and cell death. In this review, we discuss previous studies and show purinergic signaling as an important issue to be aware of in food additives development and their correlations with the physiological functions.
Rationale and Design of RNAFH Study: Effect of Rosuvastatin (10 mg/d) on Nonalcoholic Fatty Liver in Metabolic Syndrome Patients without Overt Diabetes Evaluated by 1H-Magnetic Resonance Spectroscopy
Authors: Ping Fan , Wang Xuan , Yang Jing , Zhou Mei-cen , Li Wei , Xu Ling-ling , Li Yu-xiu
Published: October 2016

Objective. The RNAFH study (effect of rosuvastatin on nonalcoholic fatty liver disease in metabolic syndrome patients without overt diabetes evaluated by 1H-MRS) is a prospective randomized, single-center, open-label trail designed to assess the effect of rosuvastatin on the intrahepatocellular lipid (IHCL) level of nonalcoholic fatty liver disease (NAFLD). Methods. 40 NAFLD patients meeting inclusion and exclusion criteria with metabolic syndrome (MS) but without overt diabetes mellitus will be included. Patients will be randomized to 52-week treatment with either rosuvastatin (10 mg/d) or blank control. The primary end point is IHCL evaluated by 1H-MRS, which was considered to be the most accurate noninvasive method for the evaluation of NAFLD. Secondary end points include homeostasis model assessment of insulin resistance (HOMA-IR) index on behalf of insulin resistance level and lipid parameters. Safety indicators will be monitored such as liver function, renal function, muscle stability, and glucose metabolism. The aims of the present study are noteworthy in respect that (1) IHCL is a quantitative indicator for evaluating the degree of fatty liver disease and 1H-MRS is a noninvasive technique to provide this specific index precisely, (2) meanwhile the HOMA-IR index and lipid parameters will be monitored, and (3) the safety of rosuvastatin treatment for 52 weeks will be evaluated including glucose metabolism, muscle stability, liver function, and renal function.
External Validation of the Cancer of the Prostate Risk Assessment Postsurgical Score for Prediction of Disease Recurrence after Radical Prostatectomy
Authors: Yıkılmaz Taha Numan , Öztürk Erdem , Güven Eşref Oğuz , Başar Halil
Published: October 2016

Objective. The cancer of the prostate risk assessment (CAPRA-S) postsurgical score predicts recurrence, metastasis, and cancer-specific survival after radical prostatectomy (RP). We evaluated the relation between CAPRA-S score and biochemical recurrence (BCR) in prostate cancer after RP in our clinic.Materials and Methods. This study was performed on 203 patients with prostate carcinoma who underwent open RP and regional lymph node dissection in our clinic between 2008 and 2013. We calculated the CAPRA-S scores including prostate-specific antigen (PSA) at diagnosis, pathology Gleason score, surgical margin, seminal vesicle invasion, extracapsular extension, and lymph node involvement. The patients were divided into 3 risk groups (low, intermediate, and high risk) according to risk scores.Results. Recurrence occurred in 17.8% of the patients (36 patients out of 203 patients) with a median of 11.7-month follow-up. The average recurrence-free survival time is 44.6 months. Surgical margin invasion and seminal vesicle invasion significantly correlated with BCR especially in high risk group (11 and 13 of 15 patients,p<0.05, resp.).Conclusion. CAPRA-S score can be easily calculated and it is useful in clinical practice in order to timely propose adjuvant therapies after surgery.
Carbohydrate Moieties and Cytoenzymatic Characterization of Hemocytes in Whiteleg ShrimpLitopenaeus vannamei
Authors: Estrada Norma , Velázquez Edwin , Rodríguez-Jaramillo Carmen , Ascencio Felipe
Published: October 2016

Hemocytes represent one of the most important defense mechanisms against foreign material in Crustacea and are also involved in a variety of other physiological responses. Fluorescent lectin-binding assays and cytochemical reactions were used to identify specificity and distribution of carbohydrate moieties and presence of several hydrolytic enzymes, in hemocytes of whiteleg shrimpLitopenaeus vannamei. Two general classes of circulating hemocytes (granular and agranular) exist inL. vannamei, which express carbohydrates residues for FITC-conjugated lectins WGA, LEA, and PNA; UEA and Con-A were not observed. Enzymatic studies indicated that acid phosphatase, nonspecific esterase, and specific esterases were present; alkaline phosphatase was not observed. The enzymes and carbohydrates are useful tools in hemocyte classification and cellular defense mechanism studies.
Impact of Anti-Inflammatory Drugs on Pyogenic Vertebral Osteomyelitis: A Prospective Cohort Study
Authors: Dinh Aurélien , Jean Maxime , Bouchand Frédérique , Davido Benjamin , Descatha Alexis , Duran Clara , Gras Guillaume , Perronne Christian , Mulleman Denis , Salomon Jérôme , Bernard Louis
Published: October 2016

Objective. Pyogenic vertebral osteomyelitis (PVO) are frequently misdiagnosed and patients often receive anti-inflammatory drugs for their back pain. We studied the impact of these medications. Methods. We performed a prospective study enrolling patients with PVO and categorized them depending on their drugs intake. Then, we compared diagnosis delay, clinical presentation at hospitalization, incidence of complications, and cure rate. Results. In total, 79 patients were included. Multivariate analysis found no correlation between anti-inflammatory drug intake and diagnosis delay, clinical presentation, complications, or outcome. Conclusion. Anti-inflammatory drugs intake does not affect diagnostic delay, severity at diagnosis, or complications of PVO.
Necrotizing Sialometaplasia of the Hard Palate in a Patient Treated with Topical Nonsteroidal Anti-Inflammatory Drug
Authors: Gatti Alessandro , Broccardo Emanuele , Poglio Giuseppe , Benech Arnaldo
Published: October 2016

Necrotizing sialometaplasia is a rare, benign, self-limiting, necrotizing process involving the minor salivary glands, mainly the mucoserous glands of the hard palate. It is thought to be the result of an ischemic event of the vasculature supplying the salivary gland lobules. Some predisposing factors such as smoking, use of alcohol, denture wearing, recent surgery, traumatic injuries, respiratory infections, systemic diseases bulimia, and anorexia have been described. Herein we present a case of necrotizing sialometaplasia of the hard palate in a patient without known predisposing factors, in our opinion, resulting from the use of topical anti-inflammatory drug. After diagnosis, the patient underwent treatment with chlorhexidine gluconate and a full palatal acrylic guard to protect the exposed bone from food residues during meals. After the sixth week the lesion regressed.
miR-20b Inhibits T Cell Proliferation and Activation via NFAT Signaling Pathway in Thymoma-Associated Myasthenia Gravis
Authors: Xin Yanzhong , Cai Hongfei , Lu Tianyu , Zhang Yan , Yang Yue , Cui Youbin
Published: October 2016

Purpose. We examined the role of miR-20b in development of thymoma-associated myasthenia gravis, especially in T cell proliferation and activation.Materials and Methods. Using qRT-PCR, we assessed expression levels of miR-20b and its target genes in cultured cells and patient samples and examined the proliferation of cultured cells, using MTT cell proliferation assays and flow cytometry based cell cycle analysis. Activation of T cells was determined by both flow cytometry and qRT-PCR of activation-specific marker genes.Results. Expression of miR-20b was downregulated in samples of thymoma tissues and serum from patients with thymoma-associated myasthenia gravis. In addition, T cell proliferation and activation were inhibited by ectopic overexpression of miR-20b, which led to increased T cell proliferation and activation. NFAT5 and CAMTA1 were identified as targets of miR-20b. Expression levels of NFAT5 and CAMTA1 were inhibited by miR-20b expression in cultured cells, and the expression levels of miR-20b and NFAT5/CAMTA1 were inversely correlated in patients with thymoma-associated myasthenia gravis.Conclusion. miR-20b acts as a tumor suppressor in the development of thymoma and thymoma-associated myasthenia gravis. The tumor suppressive function of miR-20b in thymoma could be due to its inhibition of NFAT signaling by repression of NFAT5 and CAMTA1 expression.
Hyperplanes That Intersect Each Ray of a Cone Once and a Banach Space Counterexample
Authors: McCarthy Chris
Published: October 2016

Suppose C is a cone contained in real vector space V. When does V contain a hyperplane H that intersects each of the 0-rays in C∖{0} exactly once? We build on results found in Aliprantis, Tourky, and Klee Jr.’s work to give a partial answer to this question. We also present an example of a salient, closed Banach space cone C for which there does not exist a hyperplane that intersects each 0-ray in C∖{0} exactly once.
Magnesium-Based Absorbable Metal Screws for Intra-Articular Fracture Fixation
Authors: Biber Roland , Pauser Johannes , Geßlein Markus , Bail Hermann Josef
Published: October 2016

MAGNEZIX® (Syntellix AG, Hanover, Germany) is a biodegradable magnesium-based alloy (MgYREZr) which is currently used to manufacture bioabsorbable compression screws. To date, there are very few studies reporting on a limited number of elective foot surgeries using this innovative implant. This case report describes the application of this screw for osteochondral fracture fixation at the humeral capitulum next to a loose radial head prosthesis, which was revised at the same time. The clinical course was uneventful. Degradation of the magnesium alloy did not interfere with fracture healing. Showing an excellent clinical result and free range-of-motion, the contour of the implant was still visible in a one-year follow-up.
Eating Disorders and Breast Cancer
Authors: O'Brien Katie M. , Whelan Denis R. , Sandler Dale P. , Weinberg Clarice R.
Published: October 2016

Background: Eating disorders such as anorexia nervosa and bulimia nervosa affect overall and reproductive health and may also affect breast cancer risk. We studied the association between self-reported eating disorders and breast cancer risk in a prospective cohort study.

Methods: In 2003–2009, the Sister Study enrolled women ages 35–74 years who had a sister with breast cancer but had never had it themselves. Using data from 47,813 women, we estimated adjusted HRs and 95% confidence intervals (CI) for the association between eating disorders and invasive breast cancer over a median of 5.4 years of follow-up.

Results: Three percent (n = 1,569) of participants reported a history of an eating disorder. Compared with women who never had an eating disorder, women who reported eating disorders in the past had reduced breast cancer risk (HR = 0.62; 95% CI, 0.42–0.92).

Conclusions: In this large prospective, observational cohort study, we observed an inverse association between having a history of an eating disorder and invasive breast cancer.

Impact: Historical eating disorders may be associated with a long-term reduction in breast cancer risk. Cancer Epidemiol Biomarkers Prev; 26(2); 206–11. ©2016 AACR.
A Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients
Authors: van Vlodrop Iris J.H. , Joosten Sophie C. , De Meyer Tim , Smits Kim M. , Van Neste Leander , Melotte Veerle , Baldewijns Marcella M.L.L. , Schouten Leo J. , van den Brandt Piet A. , Jeschke Jana , Yi Joo Mi , Schuebel Kornel E. , Ahuja Nita , Herman James G. , Aarts Maureen J. , Bosman Fred T. , Van Criekinge Wim , van Engeland Manon
Published: October 2016

Purpose: The currently used prognostic models for patients with nonmetastatic clear cell renal cell carcinoma (ccRCC) are based on clinicopathologic features and might be improved by adding molecular markers. Epigenetic alterations occur frequently in ccRCC and are promising biomarkers. The aim of this study is to identify prognostic promoter methylation markers for ccRCC.

Experimental Design: We integrated data generated by massive parallel sequencing of methyl-binding domain enriched DNA and microarray-based RNA expression profiling of 5-aza-2′-deoxycytidine–treated ccRCC cell lines to comprehensively characterize the ccRCC methylome. A selection of the identified methylation markers was evaluated in two independent series of primary ccRCC (n = 150 and n = 185) by methylation-specific PCR. Kaplan–Meier curves and log-rank tests were used to estimate cause-specific survival. HRs and corresponding 95% confidence intervals (CI) were assessed using Cox proportional hazard models. To assess the predictive capacity and fit of models combining several methylation markers, HarrellC statistic and the Akaike Information Criterion were used.

Results: We identified four methylation markers, that is, GREM1, NEURL, LAD1, and NEFH, that individually predicted prognosis of patients with ccRCC. The four markers combined were associated with poorer survival in two independent patient series (HR, 3.64; 95% CI, 1.02–13.00 and HR, 7.54; 95% CI, 2.68–21.19). These findings were confirmed in a third series of ccRCC cases from The Cancer Genome Atlas (HR, 3.60; 95% CI, 2.02–6.40).

Conclusions: A four-gene promoter methylation marker panel consisting of GREM1, NEURL, LAD1, and NEFH predicts outcome of patients with ccRCC and might be used to improve current prognostic models. Clin Cancer Res; 23(8); 2006–18. ©2016 AACR.
Cerebrospinal Fluid Progranulin, but Not Serum Progranulin, Is Reduced in GRN-Negative Frontotemporal Dementia
Authors: Wilke Carlo , Gillardon Frank , Deuschle Christian , Hobert Markus A. , Jansen Iris E. , Metzger Florian G. , Heutink Peter , Gasser Thomas , Maetzler Walter , Blauwendraat Cornelis , Synofzik Matthis
Published: October 2016

Background and Objective: Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. Methods: Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls). All FTD patients were assessed by whole-exome sequencing for GRN mutations, yielding a target cohort of 34 patients without pathogenic mutations in GRN (GRN-negative cohort) and 3 GRN mutation carriers (2 LoF variants and 1 novel missense variant). Results: Not only the GRN mutation carriers but also the GRN-negative patients showed decreased CSF levels of progranulin (serum levels in GRN-negative patients were normal). The decreased CSF progranulin levels were unrelated to patients' increased CSF levels of total tau, possibly indicating different destructive neuronal processes within FTD neurodegeneration. The patient with the novel GRN missense variant (c.1117C>T, p.P373S) showed substantially decreased CSF levels of progranulin, comparable to the 2 patients with GRN LoF mutations, suggesting a pathogenic effect of this missense variant. Conclusions: Our results indicate that central nervous progranulin reduction is not restricted to the relatively rare cases of FTD caused by GRN LoF mutations, but also contributes to the more common GRN-negative forms of FTD. Central nervous progranulin reduction might reflect a partially distinct pathogenic mechanism underlying FTD neurodegeneration and is not directly linked to tau alterations.
Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data
Authors: Rhee Connie M. , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar
Published: October 2016

Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time.
Exploring New Endpoints for Patients With Heart Failure With Preserved Ejection Fraction
Authors: Butler Javed , Hamo Carine E. , Udelson James E. , Pitt Bertram , Yancy Clyde , Shah Sanjiv J. , Desvigne-Nickens Patrice , Bernstein Harold S. , Clark Richard L. , Depre Christophe , Dinh Wilfried , Hamer Andrew , Kay-Mugford Patricia , Kramer Frank , Lefkowitz Martin , Lewis Kelly , Maya Juan , Maybaum Simon , Patel Mahesh J. , Pollack Pia S. , Roessig Lothar , Rotman Sarit , Salsali Afshin , Sims J. Jason , Senni Michele , Rosano Giuseppe , Dunnmon Preston , Stockbridge Norman , Anker Stefan D. , Zile Michael R. , Gheorghiade Mihai
Published: October 2016

The epidemiological, clinical, and societal implications of the heart failure (HF) epidemic cannot be overemphasized. Approximately half of all HF patients have HF with preserved ejection fraction (HFpEF). HFpEF is largely a syndrome of the elderly, and with aging of the population, the proportion of patients with HFpEF is expected to grow. Currently, there is no drug known to improve mortality or hospitalization risk for these patients. Besides mortality and hospitalization, it is imperative to realize that patients with HFpEF have significant impairment in their functional capacity and their quality of life on a daily basis, underscoring the need for these parameters to ideally be incorporated within a regulatory pathway for drug approval. Although attempts should continue to explore therapies to reduce the risk of mortality or hospitalization for these patients, efforts should also be directed to improve other patient-centric concerns, such as functional capacity and quality of life. To initiate a dialogue about the compelling need for and the challenges in developing such alternative endpoints for patients with HFpEF, the US Food and Drug Administration on November 12, 2015, facilitated a meeting represented by clinicians, academia, industry, and regulatory agencies. This document summarizes the discussion from this meeting.
MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin
Authors: Di Gregoli Karina , Mohamad Anuar Nur Najmi , Bianco Rosaria , White Stephen J. , Newby Andrew C. , George Sarah J. , Johnson Jason L.
Published: October 2016

Rationale:

Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood.

Objective:

To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms.

Methods and Results:

Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of
Apoe
−
/−
and
Ldlr
−/−
, we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II–infused
Apoe
−/−
and
Ldlr
−/−
mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in
Timp3
−/−
mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis.

Conclusions:

Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of atherosclerosis and aneurysms and protecting them from rupture.
Glycerophosphocholine Metabolites and Cardiovascular Disease Risk Factors in Adolescents
Authors: Syme Catriona , Czajkowski Simon , Shin Jean , Abrahamowicz Michal , Leonard Gabriel , Perron Michel , Richer Louis , Veillette Suzanne , Gaudet Daniel , Strug Lisa , Wang Yun , Xu Hongbin , Taylor Graeme , Paus Tomas , Bennett Steffany , Pausova Zdenka
Published: October 2016

Background:

Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia.

Methods:

We studied a population-based sample of 990 adolescents (12–18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680m/zrange. We measured VF with MRI.

Results:

We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF (P=1.4×10–19), blood pressure (P=7.7×10–5), and fasting triacylglycerols (P=9.0×10–5), and PC14:1/0:0 was positively associated with VF (P=3.0×10–7), fasting insulin (P=5.4×10–32), and triacylglycerols (P=1.4×10–29). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes,Pvalues<1.3×10–3). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs.

Conclusions:

We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk.
Toward the Green Comfort Zone: Synergy in Environmental Official Development Assistance
Authors: Park Jeongwon Bourdais
Published: October 2016

This forum article discusses environmental official development assistance (ODA), the official aid allocated for the purpose of making environmental improvements in recipient countries, focusing on the affinity between the changing ODA rules and the patterns of green aid activities at a global level. It explores the question of how far ODA rules and principles can consistently accommodate the interface between aid and the environment, through examining the changing ODA principles reflected in the outcome of the Fourth High Level Forum on Aid Effectiveness (HLF4), held in Busan in 2011–2012. This article argues that the shifting emphasis and the subsequent laxness in ODA norms may increasingly facilitate donor-oriented green-labeled projects that, in turn, create and reinforce a negative synergy with an undesirable aid modality. If ODA in this field were better managed, it could serve as a significant tool for improving the quality of life through environmental protection in poorer countries.
Leadership and the Energiewende: German Leadership by Diffusion
Authors: Steinbacher Karoline , Pahle Michael
Published: October 2016

The German energy transition—or Energiewende—stands out globally as one of the most prominent and widely discussed plans to transform an energy system. However, the ways in which Germany can and does promote the diffusion of its model remain to be systematically reviewed. Aiming at closing this gap, this article develops an analytical framework for “leadership by diffusion” and applies it to the Energiewende. We find that, while Germany’s aim of gaining followers has led to it becoming a highly active leader, a comprehensive strategy for effective leadership is still to emerge. Tapping the full potential of Energiewende leadership will require bundling existing initiatives and strengthening the availability of information on this transformation in the making. At the domestic level, the implementation of the Energiewende in Germany will need to consider the policy model’s abilities to trigger innovation and generate knowledge and lessons that can facilitate policy action elsewhere.