bluuebunny/crossref_metadata_2025 huggingface dataset:
The CECARI Study: Everolimus (Certican®) Initiation and Calcineurin Inhibitor Withdrawal in Maintenance Heart Transplant Recipients with Renal Insufficiency: A Multicenter, Randomized Trial
Authors: Van Keer Jan , Derthoo David , Van Caenegem Olivier , De Pauw Michel , Nellessen Eric , Duerinckx Nathalie , Droogne Walter , Vörös Gábor , Meyns Bart , Belmans Ann , Janssens Stefan , Van Cleemput Johan , Vanhaecke Johan
Published: February 2017

In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30–60 mL/min/1.73 m2) were randomized to start everolimus with CNI withdrawal (N=29) or continue their current CNI-based immunosuppression (N=28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p=0.18). In the on-treatment analysis, the difference did reach statistical significance (+9.4 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p=0.047). The composite safety endpoint of all-cause mortality, major adverse cardiovascular events, or treated acute rejection was not different between groups. Nonfatal adverse events occurred in 96.6% of patients in the everolimus group and 57.1% in the CNI group (p<0.001). Ten patients (34.5%) in the everolimus group discontinued the study drug during follow-up due to adverse events. The poor adherence to the everolimus therapy might have masked a potential benefit of CNI withdrawal on renal function.
Risk Factors for Additional Surgery after Iatrogenic Perforations due to Endoscopic Submucosal Dissection
Authors: Kim Gi Jun , Park Sung Min , Kim Joon Sung , Ji Jeong Seon , Kim Byung Wook , Choi Hwang
Published: February 2017

Objectives. Endoscopic resection (ER) is commonly performed to treat gastric epithelial neoplasms and subepithelial tumors. The aim of this study was to predict the risk factors for surgery after ER-induced perforation. Methods. We retrospectively reviewed the data on patients who received gastric endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) between January 2010 and March 2015. Patients who were confirmed to have perforation were classified into surgery and nonsurgery groups. We aimed to determine the risk factors for surgery in patients who developed iatrogenic gastric perforations. Results. A total of 1183 patients underwent ER. Perforation occurred in 69 (5.8%) patients, and 9 patients (0.8%) required surgery to manage the perforation. In univariate analysis, anterior location of the lesion, a subepithelial lesion, two or more postprocedure pain killers within 24 hrs, and increased heart rate within 24 hrs after the procedure were the factors related to surgery. In logistic regression analysis, the location of the lesion at the anterior wall and using two or more postprocedure pain killers within 24 hrs were risk factors for surgery. Conclusion. Most cases of perforations after ER can be managed conservatively. When a patient requires two or more postprocedure pain killers within 24 hrs and the lesion is located on the anterior wall, early surgery should be considered instead of conservative management.
Anesthetic Considerations in a Patient with Myotonic Dystrophy for Hip Labral Repair
Authors: Go Ramon , Wang David , Ludwin Danielle
Published: February 2017

Myotonic Dystrophy (DM) affects multiple organ systems. Disorders such as hyperthyroidism, progressive musculoskeletal weakness, cardiac dysrhythmias, hypoventilation, and cognitive-behavioral disorders may be present in these patients. Thorough preoperative assessment and anesthetic planning are required to minimize the risk of anesthetic complications. Patients with DM can exhibit exquisite sensitivity to sedatives, neuromuscular blocking agents, and volatile anesthetics, resulting in potential postoperative complications. There is limited literature available on successful anesthetic techniques for the DM patient. We present this case report to add to our current fund of knowledge.
A Novel Green Synthesis of Thalidomide and Analogs
Authors: Benjamin Ellis , Hijji Yousef M.
Published: February 2017

Thalidomide and its derivatives are currently under investigation for their antiangiogenic, immunomodulative, and anticancer properties. Current methods used to synthesize these compounds involve multiple steps and extensive workup procedures. Described herein is an efficient microwave irradiation green synthesis method that allows preparation of thalidomide and its analogs in a one-pot multicomponent synthesis system. The multicomponent synthesis system developed involves an array of cyclic anhydrides, glutamic acid, and ammonium chloride in the presence of catalytic amounts of 4-N,N-dimethylaminopyridine (DMAP) to produce thalidomide and structurally related compounds within minutes in good isolated yields.
Chaos Suppression of an Electrically Actuated Microresonator Based on Fractional‐Order Nonsingular Fast Terminal Sliding Mode Control
Authors: Han Jianxin , Zhang Qichang , Wang Wei , Jin Gang , Qi Houjun , Li Qiu
Published: February 2017

This paper focuses on chaos suppression strategy of a microresonator actuated by two symmetrical electrodes. Dynamic behavior of this system under the case where the origin is the only stable equilibrium is investigated first. Numerical simulations reveal that system may exhibit chaotic motion under certain excitation conditions. Then, bifurcation diagrams versus amplitude or frequency of AC excitation are drawn to grasp system dynamics nearby its natural frequency. Results show that the vibration is complex and may exhibit period‐doubling bifurcation, chaotic motion, or dynamic pull‐in instability. For the suppression of chaos, a novel control algorithm, based on an integer‐order nonsingular fast terminal sliding mode and a fractional‐order switching law, is proposed. Fractional Lyapunov Stability Theorem is used to guarantee the asymptotic stability of the system. Finally, numerical results with both fractional‐order and integer‐order control laws show that our proposed control law is effective in controlling chaos with system uncertainties and external disturbances.
An Application of the Coherent Noise Model for the Prediction of Aftershock Magnitude Time Series
Authors: Christopoulos Stavros-Richard G. , Sarlis Nicholas V.
Published: February 2017

Recently, the study of the coherent noise model has led to a simple (binary) prediction algorithm for the forthcoming earthquake magnitude in aftershock sequences. This algorithm is based on the concept of natural time and exploits the complexity exhibited by the coherent noise model. Here, using the relocated catalogue from Southern California Seismic Network for 1981 to June 2011, we evaluate the application of this algorithm for the aftershocks of strong earthquakes of magnitudeM≥6. The study is also extended by using the Global Centroid Moment Tensor Project catalogue to the case of the six strongest earthquakes in the Earth during the last almost forty years. The predictor time series exhibits the ubiquitous1/fnoise behavior.
Modelling of the Deformation Diffusion Areas on a Para-Aramid Fabric with B-Spline Curves
Authors: Kuşak Samancı Hatice , Yağcı Filiz , Çalişkan Ali
Published: February 2017

The geometrical modelling of the planar energy diffusion behaviors of the deformations on a para-aramid fabric has been performed. In the application process of the study, in the experimental period, drop test with bullets of different weights has been applied. The B-spline curve-generating technique has been used in the study. This is an efficient method for geometrical modelling of the deformation diffusion areas formed after the drop test. Proper control points have been chosen to be able to draw the borders of the diffusion areas on the fabric which is deformed, and then the De Casteljau and De Boor algorithms have been used. The Holditch area calculation according to the beams taken at certain fixed lengths has been performed for the B-spline border curve obtained as a closed form. After the calculations, it has been determined that the diffusion area where the bullet with pointed end was dropped on a para-aramid fabric is bigger and the diffusion area where the bullet with rounded end was dropped is smaller when compared with the areas where other bullets with different ends were dropped.
Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis
Authors: Qiu Zhenzhen , Zheng Kai , Zhang Haoxiang , Feng Ji , Wang Lizhi , Zhou Hao
Published: February 2017

Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients’ health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits.
Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation
Authors: Endale Mehari , Kim Tae-Hwan , Kwak Yi-Seong , Kim Na-Mi , Kim Seung-Hyung , Cho Jae Youl , Yun Bong-Sik , Rhee Man-Hee
Published: February 2017

Torilin, a sesquiterpene isolated from the fruits ofTorilis japonica,has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin’s effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1β, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2,P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBαdegradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound’s potential as a candidate anti-inflammatory agent.
Comparison of Progression Rate of Retinal Pigment Epithelium Loss in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Aflibercept
Authors: Wons Juliana , Wirth Magdalena A. , Graf Nicole , Becker Matthias D. , Michels Stephan
Published: February 2017

Purpose. Retinal pigment epithelium (RPE) loss in neovascular age-related macular degeneration (nAMD) seem to have a linear progression but might be influenced by the treatment. The purpose of the study is the comparison of RPE loss over three years in patients treated with intravitreal ranibizumab to patients who were switched to aflibercept. Methods. A retrospective analysis with 96 eyes switched to aflibercept was conducted. The progression rate of RPE loss was evaluated in patients who showed atrophy one year prior to switch (n=17) or on switch date (n=19). The RPE loss was evaluated by spectral domain optical coherence tomography (SD-OCT). Further, 22 eyes from patients treated with ranibizumab were compared. Results. The median yearly progression of RPE loss after square root transformation showed no significant difference in the year prior to switch compared to the year after switch (p=0.854). In patients who received only ranibizumab, the median yearly progression of RPE loss was 0.15 mm/y, for aflibercept patients, 0.13 mm/y. This difference was not statistically significant (p=0.172). Conclusions. There seems to be a linear progression rate of RPE loss in patients treated with ranibizumab as well as in patients with aflibercept. No significant increase of progression rate was found after switch to aflibercept.
Prevalence and Antimicrobial Susceptibility Pattern ofE. coliO157:H7 Isolated from Traditionally Marketed Raw Cow Milk in and around Asosa Town, Western Ethiopia
Authors: Disassa Nigatu , Sibhat Berhanu , Mengistu Shimelis , Muktar Yimer , Belina Dinaol
Published: February 2017

A cross-sectional study was conducted from October 2014 to July 2015 to determine the prevalence and populations ofE. colias well as the prevalence and antimicrobial susceptibility ofE. coliO157:H7 isolated from raw milk. Biochemical and serological tests methods were used to confirmE. coliandE. coliO157:H7 and isolates were subjected to antimicrobial susceptibility test using the agar disc diffusion method. Out of 380 raw milk samples examined, 129 (33.9%) and 11 (2.9%) were contaminated withE. coliandE. coliO157:H7, respectively. The highest prevalence was recorded in samples obtained from vendors (39.1%, 4.978 ± 0.180 log10/ml) compared with samples from farmers (28.1%, 3.93 ± 0.01 log10/ml) with significant differences(P=0.02). The frequency of contamination was higher in the samples collected from milk that was stored and transported in plastic containers (39.4%) than in the containers made of stainless steel (23.0%)(P=0.002). The antimicrobial susceptibility profile showed thatE. coliO157:H7 were resistant to tetracycline (81.8%), streptomycin (81.8%), and kanamycin (63.6%). Milk samples were produced and handled under poor hygienic conditions, stored, and transported in inappropriate containers and under temperature abuse conditions leading to high health risk to the consumers. Additional studies would be needed to establish association between the occurrences ofE. coliO157:H7 in raw milk and all the risk factors involved in and around Asosa town.
Guideline-Based Early Detection of Chronic Obstructive Pulmonary Disease in Eight Danish Municipalities: The TOP-KOM Study
Authors: Hemmingsen Ulla Borup , Stycke Margit , Dollerup Jens , Poulsen Peter Bo
Published: February 2017

Background. Early detection of chronic obstructive pulmonary disease (COPD) and prevention of disease progression are important. Only 40% of COPD cases are diagnosed in Denmark. Recommendations for early case finding have been established. This study investigates early detection of pulmonary obstruction in a Danish municipality setting. Methods. Eight municipalities participated. Citizens fulfilling national case finding recommendations, age ≥35 years, smokers/ex-smokers/relevant occupational exposure, and at least one respiratory symptom, were invited to spirometry. Citizens with indication of pulmonary obstruction, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.70, were referred to their general practitioner (GP). Results. 1,499 citizens were examined (53.6% male, mean age 57.2 years). 44.8% were current smokers with 57% planning for smoking cessation. The citizens recorded significant airway symptoms with dyspnea being the most important (71%). The mean FEV1/FVC score was 73.54 (SD 22.84). 456 citizens (30.4%) were found to have indication for pulmonary obstruction and were referred to GP for further diagnosis. Conclusion. Early detection in Danish municipalities proved effective finding nearly 1/3 being pulmonary obstructive. It seems to be of value to have municipalities to perform case finding together with smoking cessation as a primary intervention in COPD management.
Combination of Navigated Macular Laser Photocoagulation and Anti-VEGF Therapy: Precise Treatment for Macular Edema under Dry Retinal Conditions
Authors: Boiko Ernest V. , Maltsev Dmitrii S.
Published: February 2017

Purpose. To compare the controllability of navigated macular laser photocoagulation (MLP) in dry versus edematous retina and validate that pretreatment diagnostic images can be used as basis for navigated MLP after the macular edema (ME) has been resolved.Materials and Methods. Group 1 was divided into subgroup 1 (dry retina MLP) and subgroup 2 (MLP in ME) for comparisons of laser-burn diameters. In group 2, the areas and locations of ME before an intravitreal injection of anti-VEGF (IVAV) were compared with those of recurrent ME.Results. The average actual diameter as percentage of planned diameter of laser burn in subgroup 1 (11 DME eyes, 6 BRVO eyes) versus subgroup 2 (5 DME eyes, 8 BRVO eyes) was 115.1 ± 9.1% versus 167.2 ± 13.8% (based on retro-mode scanning laser ophthalmoscopy), and 118.1 ± 14.8% versus 176.1 ± 11.6% (based on OCT) (p<0.001). In group 2 (6 DME eyes, 6 BRVO eyes), difference in mean ME area before IVAV and that in recurrent edema was insignificant (p>0.05).Conclusion. The controllability of navigated MLP in dry retina is improved compared to edematous retina. This study validates that pretreatment diagnostic images can be used as basis for navigated MLP after the edema has been resolved.
Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology?
Authors: Adamczyk-Sowa Monika , Medrek Aldona , Madej Paulina , Michlicka Wirginia , Dobrakowski Pawel
Published: February 2017

Aim.Evaluation of the impact of gut microflora on the pathophysiology of MS.Results. The etiopathogenesis of MS is not fully known. Gut microbiota may be of a great importance in the pathogenesis of MS, since recent findings suggest that substitutions of certain microbial population in the gut can lead to proinflammatory state, which can lead to MS in humans. In contrast, other commensal bacteria and their antigenic products may protect against inflammation within the central nervous system. The type of intestinal flora is affected by antibiotics, stress, or diet. The effects on MS through the intestinal microflora can also be achieved by antibiotic therapy andLactobacillus. EAE, as an animal model of MS, indicates a strong influence of the gut microbiota on the immune system and shows that disturbances in gut physiology may contribute to the development of MS.Conclusions.The relationship between the central nervous system, the immune system, and the gut microbiota relates to the influence of microorganisms in the development of MS. A possible interaction between gut microbiota and the immune system can be perceived through regulation by the endocannabinoid system. It may offer an opportunity to understand the interaction comprised in the gut-immune-brain axis.
Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives
Authors: Szopa Wojciech , Burley Thomas A. , Kramer-Marek Gabriela , Kaspera Wojciech
Published: February 2017

Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3–5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated. Some of them, such as IDH mutations, 1p19q deletion, MGMT promoter methylation, and EGFRvIII amplification are frequently tested in routine clinical practice. With the development of sequencing technology, detailed characterization of GBM molecular signatures has facilitated a more personalized therapeutic approach and contributed to the development of a new generation of anti-GBM therapies such as molecular inhibitors targeting growth factor receptors, vaccines, antibody-based drug conjugates, and more recently inhibitors blocking the immune checkpoints. In this article, we review the exciting progress towards elucidating the potential of current and novel GBM biomarkers and discuss their implications for clinical practice.
Classification and Differential Diagnosis of Diabetic Nephropathy
Authors: Qi Chenyang , Mao Xing , Zhang Zhigang , Wu Huijuan
Published: February 2017

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review.
A Novel Graph Constructor for Semisupervised Discriminant Analysis: Combined Low-Rank and k-Nearest Neighbor Graph
Authors: Zu Baokai , Xia Kewen , Pan Yongke , Niu Wenjia
Published: February 2017

Semisupervised Discriminant Analysis (SDA) is a semisupervised dimensionality reduction algorithm, which can easily resolve the out-of-sample problem. Relative works usually focus on the geometric relationships of data points, which are not obvious, to enhance the performance of SDA. Different from these relative works, the regularized graph construction is researched here, which is important in the graph-based semisupervised learning methods. In this paper, we propose a novel graph for Semisupervised Discriminant Analysis, which is called combined low-rank and k-nearest neighbor (LRKNN) graph. In our LRKNN graph, we map the data to the LR feature space and then the kNN is adopted to satisfy the algorithmic requirements of SDA. Since the low-rank representation can capture the global structure and the k-nearest neighbor algorithm can maximally preserve the local geometrical structure of the data, the LRKNN graph can significantly improve the performance of SDA. Extensive experiments on several real-world databases show that the proposed LRKNN graph is an efficient graph constructor, which can largely outperform other commonly used baselines.
An Improved Grey Wolf Optimization Strategy Enhanced SVM and Its Application in Predicting the Second Major
Authors: Wei Yan , Ni Ni , Liu Dayou , Chen Huiling , Wang Mingjing , Li Qiang , Cui Xiaojun , Ye Haipeng
Published: February 2017

In order to develop a new and effective prediction system, the full potential of support vector machine (SVM) was explored by using an improved grey wolf optimization (GWO) strategy in this study. An improved GWO, IGWO, was first proposed to identify the most discriminative features for major prediction. In the proposed approach, particle swarm optimization (PSO) was firstly adopted to generate the diversified initial positions, and then GWO was used to update the current positions of population in the discrete searching space, thus getting the optimal feature subset for the better classification purpose based on SVM. The resultant methodology, IGWO‐SVM, is rigorously examined based on the real‐life data which includes a series of factors that influence the students’ final decision to choose the specific major. To validate the proposed method, other metaheuristic based SVM methods including GWO based SVM, genetic algorithm based SVM, and particle swarm optimization‐based SVM were used for comparison in terms of classification accuracy, AUC (the area under the receiver operating characteristic (ROC) curve), sensitivity, and specificity. The experimental results demonstrate that the proposed approach can be regarded as a promising success with the excellent classification accuracy, AUC, sensitivity, and specificity of 87.36%, 0.8735, 85.37%, and 89.33%, respectively. Promisingly, the proposed methodology might serve as a new candidate of powerful tools for second major selection.
Clinical Evidence of Chinese Massage Therapy (Tui Na) for Cervical Radiculopathy: A Systematic Review and Meta‐Analysis
Authors: Wei Xu , Wang Shangquan , Li Linghui , Zhu Liguo
Published: February 2017

Objective. The review is to assess the current evidence of Chinese massage therapy (Tui Na) for cervical radiculopathy. Methods. Seven databases were searched. Randomised controlled trials incorporating Tui Na alone or Tui Na combined with conventional treatment were enrolled. The authors in pairs independently assessed the risk of bias and extracted the data. Results. Five studies involving 448 patients were included. The pooled analysis from the 3 trials indicated that Tui Na alone showed a significant lowering immediate effects on pain score (SMD = −0.58; 95% CI: −0.96 to −0.21; Z = 3.08, P = 0.002) with moderate heterogeneity compared to cervical traction. The meta‐analysis from 2 trials revealed significant immediate effects of Tui Na plus cervical traction in improving pain score (MD = −1.73; 95% CI: −2.01 to −1.44; Z = 11.98, P < 0.00001) with no heterogeneity compared to cervical traction alone. No adverse effect was reported. There was very low quality or low quality evidence to support the results. Conclusions. Tui Na alone or Tui Na plus cervical traction may be helpful to cervical radiculopathy patients, but supportive evidence seems generally weak. Future clinical studies with low risk of bias and adequate follow‐up design are recommended.
Optical Axis Perturbation Analysis for the Unit‐Magnification Multipass System
Authors: Guo Yin , Sun Liqun , Yang Zheng
Published: February 2017

The optical axis sensitivity for the unit‐magnification multipass system (UMS) is presented by using a general misaligned optical element transfer model. The generalized sensitivity factors SD1, SD2, ST1, and ST2 influenced by both the axial and angular misalignments of the objective mirrors in a UMS have been calculated for the first time. The Bernstein‐Herzberg White Cells are used as an example, and their alignment tolerance and stability properties are found when their configurations change. The analysis in this paper is helpful for the design of other kinds of multipass gas cells (MGC) with high robustness and avoiding the violent vibration of the optical axis when the misalignment of each mirror is controlled within the tolerance range. Among the five possible perturbations sources, the misaligned factors (δix, δiy, θix) have more effects on the output beam’s position and the perturbed sources from (δix, θix) and (δiy, θiy) have more impacts on the output beam’s slope referred to as x‐axis and y‐axis, respectively. Higher reflection times mean smaller tolerance range. The results benefit the multipass cell design and the precise alignment of the mirrors within the cell with the purpose of long‐term stability in measurements.
An International Evaluation of Cognitive Reserve and Memory Changes in Early Old Age in 10 European Countries
Authors: Cadar Dorina , Robitaille Annie , Clouston Sean , Hofer Scott M. , Piccinin Andrea M. , Muniz-Terrera Graciela
Published: February 2017

Background: Cognitive reserve was postulated to explain individual differences in susceptibility to ageing, offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age. Methods: Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe, were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models. Education was used as a marker of cognitive reserve and evaluated in association with memory performance and rate of change, while accounting for income, general health, smoking, body mass index, gender, and baseline age. Results: In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 [SE = 0.003] and 0.006 [SE = 0.002]), and Switzerland for immediate recall (0.006 [SE = 0.003]). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 [SE = 0.003]). Conclusions: We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment.
Elevated Nitrosative Stress in Children with Chronic Spontaneous Urticaria
Authors: Dilek Fatih , Ozceker Deniz , Ozkaya Emin , Guler Eray Metin , Yazici Mebrure , Tamay Zeynep , Kocyigit Abdurrahim , Guler Nermin
Published: February 2017

Background: Chronic spontaneous urticaria (CSU) is an idiopathic condition that seriously affects quality of life. It is well known that oxidative stress and nitrosative stress (NS) are generally involved in many chronic inflammatory diseases. This study aimed to evaluate the possible role of NS in the pathogenesis of CSU. Methods: Thirty-two children with CSU and 22 healthy control subjects were enrolled in the study. Demographic and clinical features were defined, and disease activity was quantified using the urticaria activity score (UAS). Serum NS was assessed by the plasma levels of total nitric oxide (NOx) metabolites and nitrite and nitrate measurements using a Griess method-based commercial kit. Results: Plasma NOx levels were 82.5 ± 11.3 µmol/L in the CSU group and 50.9 ± 9.4 µmol/L in the control group. The difference was statistically significant (p < 0.001). CSU patients also had higher plasma nitrite levels than controls (53.3 ± 13.8 vs. 30.2 ± 10.1 µmol/L, respectively, p < 0.001). The median values of plasma nitrate were 27.5 µmol/L (IQR 19.1-35.5) in CSU patients and 20.9 µmol/L (IQR 17.9-23.2) in the control group, and the difference was statistically significant (p = 0.009). In addition, plasma NOx and nitrite levels were positively correlated with the UAS (rho = 0.512, p = 0.03 and rho = 0.452, p = 0.011, respectively). Conclusion: Plasma NS is elevated and positively correlated with disease activity in children with CSU.
Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation
Authors: Pistolesi Valentina , Zeppilli Laura , Polistena Francesca , Sacco Maria Itala , Pierucci Alessandro , Tritapepe Luigi , Regolisti Giuseppe , Fiaccadori Enrico , Morabito Santo
Published: February 2017

Aims: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. Methods: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. Results: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. Conclusions: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia.
D-Dimer Plasma Levels Parallel the Clinical Response to Omalizumab in Patients with Severe Chronic Spontaneous Urticaria
Authors: Asero Riccardo , Marzano Angelo V. , Ferrucci Silvia , Cugno Massimo
Published: February 2017

Omalizumab is very effective in the majority of patients with severe chronic spontaneous urticaria (CSU), but its mechanism of action is still unclear. In CSU the coagulation cascade is activated with an intensity that parallels the disease severity, and elevated plasma D-dimer levels are associated with a poor response to both antihistamines and cyclosporin. We measured D-dimer plasma levels before and after the first administration of omalizumab in 32 patients with severe CSU. A number of clinical and laboratory parameters were recorded, including the urticaria activity score, presence of angioedema, disease duration, C-reactive protein, anti-nuclear, and anti-thyroid antibodies. Baseline D-dimer levels were elevated in 19 (59%) cases. Omalizumab induced a complete response in 25 patients (78%), in most cases already after the first administration. At baseline, 14/25 responders had increased D-dimer plasma levels versus 5/7 non-responders. All responders showed a dramatic decrease of D-dimer plasma levels after the first administration of the drug (from 1,024 ± 248 [mean ± SE] to 251 ± 30 ng/mL; p = 0.003). In contrast, non-responders did not show any reduction in D-dimer levels after omalizumab administration (from 787 ± 206 to 1,230 ± 429 ng/mL; p = ns). In conclusion, plasma levels of D-dimer are frequently elevated in patients with severe CSU before omalizumab administration and decrease according to the clinical response of the disease to the drug, suggesting a possible effect of omalizumab on coagulation activation and fibrin degradation in a subset of CSU patients.
Anticaries Potential of a Sodium Monofluorophosphate Dentifrice Containing Calcium Sodium Phosphosilicate: Exploratory in situ Randomized Trial
Authors: Parkinson Charles R. , Siddiqi Muhammad , Mason Stephen , Lippert Frank , Hara Anderson T. , Zero Domenick T.
Published: February 2017

Calcium sodium phosphosilicate (CSPS) is a bioactive glass material that alleviates dentin hypersensitivity and is postulated to confer remineralization of caries lesions. This single-centre, randomized, single (investigator)-blind, placebo-controlled, crossover, in situ study explored whether the addition of 5% CSPS to a nonaqueous fluoride (F) such as sodium monofluorophosphate (SMFP)-containing dentifrice affects its cariostatic ability. Seventy-seven subjects wore 4 gauze-covered enamel specimens with preformed lesions (2 surface-softened and 2 subsurface) placed buccally on their mandibular bilateral dentures for up to 4 weeks. Subjects brushed twice daily with 1 of the 5 study dentifrices: 927 ppm F/5% CSPS, 927 ppm F/0% CSPS, 250 ppm F/0% CSPS, 0 ppm F/5% CSPS, or 0 ppm F/0% CSPS. Specimens were retrieved after either 21 (surface-softened lesions; analyzed by Knoop surface microhardness [SMH]) or 28 days (subsurface lesions; analyzed by transverse microradiography). The enamel fluoride uptake was determined for all specimens using a microbiopsy technique. The concentrations of fluoride and calcium in gauze-retrieved plaque were also evaluated. Higher dentifrice fluoride concentrations led to greater remineralization and fluoridation of both lesion types and increased plaque fluoride concentrations. CSPS did not improve the cariostatic properties of SMFP; there were no statistically significant differences between 927 ppm F/5% CSPS and 927 ppm F/0% CSPS in percent SMH recovery (p = 0.6788), change in integrated mineral loss (p = 0.5908), or lesion depth (p = 0.6622). Likewise, 0 ppm F/5% CSPS did not provide any benefits in comparison to 0 ppm F/0% CSPS. In conclusion, CSPS does not negatively impact nor does it improve the ability of an SMFP dentifrice to affect remineralization of caries lesions.
Identification of Herb Pairs in Esophageal Cancer
Authors: Cai Yu-Mei , Zhu Hui , Niu Jing-Xiu , Bing Lin , Sun Zhen , Zhang Wen-Hua , Ying Jian-Zi , Yin Xiao Dong , Li Jing , Pang Yan , Li Jia-Li
Published: February 2017

Background: Chinese herbal medicine (CHM) is used widely to treat various diseases, including cancer. However, effective herb pairs for treating specific cancer types have so far not been identified. Here, we aimed to calculate the survival benefits of herb pairs by cluster analysis, association rules, and survival evaluation in patients with esophageal cancer (EC) treated with CHM. Patients and Methods: 59 patients with EC who received 176 prescriptions including 178 types of herbs were enrolled into the study. The herb pairs were identified by both cluster analysis and association rules. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Eight groups of herb pairs were identified by cluster analysis, and 4 groups of herb pairs were identified by association rules. Of these, 3 groups of herb pairs were identified by both methods. OS estimation showed that the pair of chicken gizzard-membrane/Astragalus was associated with improved survival in patients with EC treated with CHM. Conclusion: Patients who received prescriptions containing the pair of chicken gizzard-membrane and Astragalus had improved OS compared with patients who received prescriptions lacking this pair.
The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent
Authors: Worm Margitta , Ernst Dennis , Kraller Markus , Babina Magda
Published: February 2017

Background: The clinical efficacy and safety of allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunological changes by allergoids versus allergens in the cells of the same individual has not been extensively performed, and the impact of concurrent Toll-like receptor 4 (TLR4) ligation has not been specified. Methods: Three types of birch allergen were utilized: glutaraldehyde-treated allergoid (extract A), the same allergoid plus monophosphoryl lipid A (MPL), i.e., TLR4 ligand (extract A*), and native allergen (extract B). Antigen-specific responses after the in vitro stimulation of blood cells with the extracts were assessed by studying costimulatory receptors on the B cell surface by flow cytometry, cytokine responses by ELISA, and CD63 and CD203c upregulation (basophil activation test) in allergic versus nonallergic subjects. Results: HLA-DR selectively increased upon allergen or allergoid treatment in the allergic group only. The extract types elicited similar cytokine responses, with IL-6 and IL-10 production detected only in certain atopic subjects. The allergoids revealed a strong reduction (100- to <10,000-fold) in basophil activation versus native allergen. Reactivity was undetectable in the basophils from nonallergic subjects. Conclusion: The allergenicity of the allergoid employed was sharply reduced when compared to the native allergen, while its immunogenicity was largely retained, especially in the presence of MPL. We also provide further evidence that allergic and nonallergic individuals show preexisting differences in their immune repertoires.
Human Allergen-Specific IgG Subclass Antibodies Measured Using ImmunoCAP Technology
Authors: Movérare Robert , Blume Karin , Lind Peter , Crevel René , Marknell DeWitt Åsa , Cochrane Stella
Published: February 2017

Background: Knowledge of human IgG subclass antibody responses to various allergens has been hampered by a lack of reliable standardized assays. The aim here was to develop quantitative immunoassays for human IgG1, IgG2, and IgG3 antibodies using ImmunoCAP® technology and to evaluate their application. Methods: Enzyme conjugates with isotype-specific monoclonal antibodies and calibrators composed of purified myeloma paraproteins were developed for each assay and used together with other standardized assay reagents for the Phadia® 100 instrument. The calibrators were adjusted to the international reference preparation IRP 67/86. The assays were characterized and used together with other standard ImmunoCAP assays to measure antibodies to various allergens in preliminary studies. Results: The new assays had limits of quantitation of 1.0 (IgG1), 4.6 (IgG2), and 0.04 mgA/L (IgG3), and coefficients of variation of <20%. Only some minor cross-reactivity with IgG2 was observed for the specific IgG1 assay. The specific IgG2 assay showed a bias for the allotype G2m(23) and compensation factors were used to adjust the measured concentrations accordingly. Preliminary studies indicated a strong and stable IgG4 antibody response to β-lactoglobulin in healthy individuals, a high IgG1 and even higher IgG2 antibody response to house dust mite in sensitized and nonsensitized subjects, and a mixed IgG subclass response to venom allergens in allergic patients with increasing IgG4 antibody levels during venom immunotherapy. Conclusions: The new research assays are valuable tools for immunological studies, enabling the characterization of antibody profiles using a standardized approach, and facilitating data interpretation and the comparison of results across studies.
Radiopathological Features and Identification of Mycobacterial Infections in Granulomatous Nodules Resected from the Lung
Authors: Sakakibara Yumi , Suzuki Yoshimi , Fujie Toshihide , Akashi Takumi , Iida Tadatsune , Miyazaki Yasunari , Eishi Yoshinobu , Inase Naohiko
Published: February 2017

Background: Pulmonary granulomas are sometimes resected because they resemble lung cancer and false-positive findings come through from positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG). Mycobacterial infection is a common cause of granulomas. Objective: The purpose of this study was to evaluate the radiopathological features and the methods for identifying mycobacterial infections in granulomatous nodules resected from the lung. Methods: Thirty-five solitary lesions resected because of suspected lung cancer were enrolled, including 22 nonfungal granulomatous lesions and 13 benign lesions as controls. The radiological, microbiological, and histological findings were reviewed. To identify mycobacterial infection, immunohistochemical (IHC) staining, IS6110 polymerase chain reaction (PCR), and real-time PCR for the detection of Mycobacterium tuberculosis (TB) were performed using formalin-fixed and paraffin-embedded tissue specimens. The correlations between the radiopathological features and the median maximum standardized uptake value (SUVmax) of 18F-FDG PET were also evaluated. Results: Mycobacteria were isolated from the cultures of 10 of the granulomatous lesions, including TB from 2 and Mycobacterium avium complex from 8. The mean size of the nodules in the culture-positive group was significantly larger than that of those in the culture-negative group (30.5 ± 13.1 vs. 15.1 ± 6.3 mm, p = 0.003). IHC stainings were positive in 15 granulomas. Eight granulomas were positive in IS6110 PCR, and 7 of them were also positive in real-time PCR. SUVmax was ≥2.5 in all of the PCR-positive granulomas. Conclusion: The most frequent cause of granulomatous lesions was mycobacterial infection. It seemed that the culture result was associated with nodule size and that the results of IS6110 were associated with 18F-FDG-uptake.
Relationship between Pulmonary Adverse Events and Everolimus Exposure in Japanese and Non-Japanese Patients: A Meta-Analysis of Oncology Trials
Authors: Noguchi Shinzaburo , Shinohara Nobuo , Ito Tetsuhide , Ohtsu Atsushi , Ravaud Alain , Jerusalem Guy , Ohno Nobutsugu , Gallo Jorge , Bouillaud Emmanuel , Fan Jenna , Nonomura Norio
Published: February 2017

Aims: This meta-analysis explores the relationship between the everolimus minimum (Cmin) and maximum (Cmax) exposure and the risk for pulmonary adverse events (AEs) in Japanese versus non-Japanese patients. Methods: Patient-level data from patients treated with daily everolimus in advanced solid tumor trials were evaluated using a Cox regression model, stratified by cancer type or treatment arm, with log-transformed time-averaged Cmin or Cmax as a time-varying covariate. Kaplan-Meier analysis was used to evaluate the relationship between pulmonary AEs and pharmacokinetic parameters. Results: Thirty studies were identified. In the Cmin population (n = 1,962), all-grade pulmonary AE incidence was significantly higher in Japanese versus non-Japanese patients (19.9 vs. 9.4%). Pharmacokinetic parameters were similar between Japanese and non-Japanese patients. A 2-fold increase in everolimus Cmin significantly increased the risk for the first any-grade pulmonary AE in Japanese (risk ratio: 1.824; 95% CI: 1.141-2.918) and non-Japanese patients (risk ratio: 1.406; 95% CI: 1.156-1.710). Conclusions: The risk for pulmonary AEs is related to everolimus exposure. Local monitoring and reporting differences might account for the significantly higher reported incidence of low-grade everolimus-associated pulmonary AEs in Japanese versus non-Japanese patients. Patients should be carefully monitored for early signs of pulmonary AEs, and appropriate medical management should be implemented.
Effect of N-Benzylpiperazine, Its Metabolite N-Benzylethylenediamine, and Its Disubstituted Analogue N,N'-Dibenzylpiperazine on the Acquisition, Formation, and Consolidation of Memory in Mice
Authors: Castillo-Hernández Juan Carlos , Velázquez-Moyado Josué A. , Reyes-Ramírez Adelfo , Ramírez-López Elena G. , González-Andrade Martín , Navarrete Andrés
Published: February 2017

Background:N-benzylpiperazine (BZP) belongs to a class of piperazine derivatives (PZDs) that have emerged as recreational drugs. These compounds increase the release of dopamine and serotonin. BZP mimics the psychoactive effects of 3,4-methylenedioxymethylamphetamine. BZP is metabolized to N-benzylethylenediamine (BEDA) and benzylamine. The compound N,N'-dibenzylpiperazine (DBZP) is obtained as a byproduct during the synthesis of BZP. Some PZDs have shown effects on memory; however, there are no previous reports on the activity of BZP, BEDA, and DBZP on memory or on a description of their neuropharmacological profile. We evaluated the effects of these compounds on acquisition, formation, and consolidation memory and explored their neuropharmacological profile in mice. Methods: We used the passive avoidance test to evaluate the nootropic effect and for memory experiments. We also evaluated the sedative, myo-relaxant, motor coordination, anxiogenic, and locomotor activity of these compounds. Results: We showed that BZP, its metabolite BEDA, and the disubstituted analogue DBZP enhance the memory and show anxiogenic effects. BZP, as well as DBZP but not BEDA, showed a strong myo-relaxant effect without impairing motor coordination. Conclusions: BZP and BEDA enhanced the acquisition and consolidation of memory, whereas DBZP only enhances the acquisition of the memory. BEDA and DBZP have an anxiogenic profile similar to that of BZP. BEDA and DBZP represent new psychoactive compounds with the potential to be new BZP-like recreational entities.