bluuebunny/crossref_metadata_2025 huggingface dataset:
Studying the Formation of Biofilms on Supports with Different Polarity and Their Efficiency to Treat Wastewater
Authors: Sfaelou Stavroula , Karapanagioti Hrissi K. , Vakros John
Published: May 2015

The main objective of this study was the evaluation of biofilm formation onto different supports and of biofilm efficiency to treat wastewater. Two different reactors were used, one with porous polyvinyl alcohol gel (PVA) biocarrier and another with a high-density polyethylene (PE) biocarrier. The reactor performance was evaluated and the biofilm formed was analyzed with potentiometric mass titrations. The biofilm formation was monitored with diffuse reflectance spectroscopy. The presence of the support did not alter the nature of the biofilm. However, the quantity of the biofilm formed was higher when polar surface groups were present on the support.
Ophthalmologic Psychophysical Tests Support OCT Findings in Mild Alzheimer’s Disease
Authors: Salobrar-Garcia Elena , de Hoz Rosa , Rojas Blanca , Ramirez Ana I. , Salazar Juan J. , Yubero Raquel , Gil Pedro , Triviño Alberto , Ramirez José M.
Published: May 2015

Purpose. To analyze in mild Alzheimer’s disease (MAD) patients, GDS-4 (Reisberg Scale), whether or not some psychophysical tests (PTs) support OCT macular findings in the same group of MAD patients reported previously.Methods. Twenty-three MAD patients and 28 age-matched control subjects with mean Mini Mental State Examination of 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision were included. Best-corrected visual acuity (VA), contrast sensitivity (CS) (3, 6, 12, and 18 cpds), color perception (CP), and perception digital test (PDT) were tested in one eye of each patient.Results. In comparison with the controls, MAD patients presented (i) a significant decrease in VA, PDT, and CS for all spatial frequencies analyzed, especially the higher ones, and (ii) a significant increase in unspecific errors on the blue axis (P<0.05in all instances). In MAD patients, a wide aROC curve was plotted in all PTs.Conclusions. In MAD, CS, VA, and the tritan axis in CP were impaired. The PTs with the greatest predictive value are the higher spatial frequencies in CS and tritan unspecific errors in CP. PT abnormalities are consistent with the structural findings reported in the same MAD patients using OCT.
Influence of Physical and Geometrical Uncertainties in the Parametric Instability Load of an Axially Excited Cylindrical Shell
Authors: Silva Frederico Martins Alves da , Brazão Augusta Finotti , Gonçalves Paulo Batista
Published: May 2015

This work investigates the influence of Young’s modulus, shells thickness, and geometrical imperfection uncertainties on the parametric instability loads of simply supported axially excited cylindrical shells. The Donnell nonlinear shallow shell theory is used for the displacement field of the cylindrical shell and the parameters under investigation are considered as uncertain parameters with a known probability density function in the equilibrium equation. The uncertainties are discretized as Hermite-Chaos polynomials together with the Galerkin stochastic procedure that discretizes the stochastic equation in a set of deterministic equations of motion. Then, a general expression for the transversal displacement is obtained by a perturbation procedure which identifies all nonlinear modes that couple with the linear modes. So, a particular solution is selected which ensures the convergence of the response up to very large deflections. Applying the standard Galerkin method, a discrete system in time domain that considers the uncertainties is obtained and solved by fourth-order Runge-Kutta method. Several numerical strategies are used to study the nonlinear behavior of the shell considering the uncertainties in the parameters. Special attention is given to the influence of the uncertainties on the parametric instability and time response, showing that the Hermite-Chaos polynomial is a good numerical tool.
Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury
Authors: Zhao Yuanyuan , Sun Xiaoxian , Cao Wenming , Ma Jie , Sun Li , Qian Hui , Zhu Wei , Xu Wenrong
Published: May 2015

This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC-) derived exosomes (hucMSC-exosomes) have a protective effect on acute myocardial infarction (AMI). Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein) were intravenously administrated immediately following ligation of the left anterior descending (LAD) coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells). The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.
Single Mobile Micro Droplet-Particle Pairs Spatially Captured by Macro Host Droplets on a Superhydrophobic Surface
Authors: Watson Gregory S. , Cribb Bronwen W. , Watson Jolanta A.
Published: May 2015

In this preliminary study, we demonstrate how small single water droplets can be spatially captured on the surface of individual micron sized hydrophobic coated particles (C18) which adhere to the surface of a nonmobile larger host water droplet resting on a superhydrophobic surface. The formation of the larger droplet, particle adhesion to that droplet, and smaller droplet formation on the particle all take place spontaneously from condensation conditions. These micro droplet-particle pairs are confined to the surface (liquid-air interface) of the larger host droplet; however, they are free to engage with external forces to promote mobility. This response may find applications for particle pair transport on liquid surfaces. We also demonstrate that droplets can be captured or removed from the larger droplet surface via a self-propulsion mechanism.
Undifferentiated Intimal Sarcoma of the Inferior Vena Cava with Extension to the Right Atrium and Renal Vasculature
Authors: Afzal Aasim M. , Alsahhar Jamil , Podduturi Varsha , Schussler Jeffrey M.
Published: May 2015

Primary sarcomas of the great vessels (aorta, pulmonary artery, and inferior vena cava (IVC)) are exceedingly rare. We report a rare case of an undifferentiated intimal sarcoma of the IVC with extension to the right atrium, adrenal, and renal veins. The patient underwent extensive resection, reconstruction of the IVC, and subsequent adjuvant chemotherapy. Patient has tolerated chemotherapy and, at 17 months after resection, the patient remains free of tumor recurrence. Undifferentiated intimal sarcomas remain a rare entity with only five cases of venous undifferentiated intimal sarcomas reported in the literature, two of which occurred in the IVC. Intimal sarcomas tend to carry a poor prognosis with the limited literature available on treatment approaches. Our objective is to highlight this rare entity and possible treatment approach which we utilized. Primary sarcomas of IVC need to be included as part of a complete differential diagnosis in patients with atrial masses or recurrent pulmonary emboli.
Overcoming Recruitment Barriers in Urban Older Adults Residing in Congregate Living Facilities
Authors: Simning Adam , van Wijngaarden Edwin , Conwell Yeates
Published: May 2015

Background. Participation of minority older adults in mental health research has been limited by mistrust, transportation difficulties, lack of knowledge, and insufficient community partnership. We describe strategies utilized to overcome these recruitment barriers.Methods. Our target population included 553 public housing residents of older adult high-rise buildings in Rochester, NY. We had a two-stage cross-sectional study: Stage 1 was a health survey for all residents and Stage 2 was a psychiatric interview of English-speaking residents aged 60 years and older. Recruitment occurred through mailings, onsite activities, and resident referrals.Results. Stage 1 had 358 participants (64.7% response) and Stage 2 had 190 (61.6% target population response), with higher participation among African Americans. We found some strategies effective for overcoming recruitment barriers. First, we partnered with a community agency and organized onsite educational activities to improve residents’ trust. Second, the study occurred entirely onsite, which facilitated participation of functionally impaired residents. Third, onsite activities allowed the residents to learn about the study and complete surveys in person. Fourth, we provided immediate incentives that resulted in many study referrals.Conclusions. Although recruitment of minority older adults presents unique challenges, a multifaceted community-tailored approach mitigated several recruitment barriers in this mental health study.
Beninese Medicinal Plants as a Source of Antimycobacterial Agents: Bioguided Fractionation andIn VitroActivity of Alkaloids Isolated fromHolarrhena floribundaUsed in Traditional Treatment of Buruli Ulcer
Authors: Yemoa Achille , Gbenou Joachim , Affolabi Dissou , Moudachirou Mansourou , Bigot André , Anagonou Séverin , Portaels Françoise , Martin Anandi , Quetin-Leclercq Joëlle
Published: May 2015

Buruli ulcer (BU) imposes a serious economic burden on affected households and on health systems that are involved in diagnosing the disease and treating patients. Research is needed to find cost-effective therapies for this costly disease. Plants have always been an important source of new pharmacologically active molecules. Consequently we decided to undertake the study of plants used in traditional treatment of BU in Benin and investigate their antimycobacterial activity as well as their chemical composition. Extracts from forty-four (44) plant species were selected on account of reported traditional uses for the treatment of BU in Benin and were assayed for antimycobacterial activities. Crude hydroethanolic extract from aerial parts ofHolarrhena floribunda(G. Don) T. Durand and Schinz was found to have significant antimycobacterial activity againstM.ulcerans(MIC = 125 µg/mL). We describe here the identification of four steroidal alkaloids fromMycobacterium ulceransgrowth-inhibiting fractions of the alkaloidal extract of the aerial parts ofHolarrhena floribunda. Holadysamine was purified in sufficient amount to allow the determination of its MCI (=50 µg/mL). These results give some support to the use of this plant in traditional medicine.
Use of MALDI-TOF MS for Identification of NontuberculousMycobacteriumSpecies Isolated from Clinical Specimens
Authors: Mediavilla-Gradolph María Concepción , De Toro-Peinado Inmaculada , Bermúdez-Ruiz María Pilar , García-Martínez María de los Ángeles , Ortega-Torres María , Montiel Quezel-Guerraz Natalia , Palop-Borrás Begoña
Published: May 2015

The aim of this study was to compare the results obtained for identification by MALDI-TOF of nontuberculous mycobacteria (NTM) isolated in clinical samples with those obtained by GenoTypeMycobacteriumCM/AS (common mycobacteria/additional species). A total of 66Mycobacteriumisolates from various clinical specimens (mainly respiratory) were tested in this study. They were identified using MALDI-TOF Bruker from strains isolated in Lowenstein, following the recommended protocol of heat inactivation and extraction, and were simultaneously analyzed through hybridization by GenoTypeMycobacteriumfrom liquid culture MGIT. Our results showed that identification by MALDI-TOF was correct in 98.4% (65/66) of NTM isolated in our clinical practice (M. avium, M. intracellulare, M. abscessus, M. chelonae, M. fortuitum, M. mucogenicum, M. kansasii, and M. scrofulaceum). MALDI-TOF was found to be an accurate, rapid, and cost-effective system for identification of mycobacteria species.
IL‐33 Aggravates DSS‐Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses
Authors: Zhu Junfeng , Yang Fangli , Sang Lixuan , Zhai Jingbo , Zhang Xiaoqing , Yue Dan , Li Shengjun , Li Yan , Lu Changlong , Sun Xun
Published: May 2015

Interleukin‐ (IL‐) 33, a member of the IL‐1 cytokine family, is an important modulator of the immune system associated with several immune‐mediated diseases. IL‐33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL‐33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin‐ (IL‐) 33 in dextran sulphate sodium‐ (DSS‐) induced acute colitis in mice using recombinant mouse IL‐33 protein (rIL‐33). We found that DSS‐induced acute colitis was aggravated by rIL‐33 treatment. rIL‐33‐treated DSS mice showed markedly reduced levels of interferon‐ (IFN‐)γ and IL‐17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL‐5 and IL‐13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL‐33 stimulated CD4+T cells and caused the cell to adopt a Th2‐type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL‐33 may be involved in pathogenesis of DSS‐induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL‐33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS‐induced acute colitis.
Efficacy of the Reactive Oxygen Species Generated by Immobilized TiO2in the Photocatalytic Degradation of Diclofenac
Authors: Di Credico B. , Bellobono I. R. , D’Arienzo M. , Fumagalli D. , Redaelli M. , Scotti R. , Morazzoni F.
Published: May 2015

We report on the photodegradation of diclofenac (DCF) by hydrothermal anatase nanocrystals either free or immobilized in porous silica matrix (TS) in connection to the type and amount of reactive oxygen species (ROS), in order to have deeper insight into their role in the photocatalysis and to provide an effective tool to implement the DCF mineralization. TiO2and TS exhibit a remarkable efficiency in the DCF abatement, supporting that the utilization of anatase nanoparticles with the highly reactive{001},{010}, and{101}exposed surfaces can be an effective way for enhancing the photooxidation even of the persistent pollutants. Furthermore, the hydrothermal TiO2, when immobilized in silica matrix, preserves its functional properties, combining high photoactivity with an easy technical use and recovery of the catalyst. The catalysts performances have been related to the presence of OH•,O21, andO2-•species by electron paramagnetic resonance spin-trap technique. The results demonstrated that the ROS concentration increases with the increase of photoactivity and indicated a significant involvement ofO21in the DCF degradation. The efficacy of TiO2when immobilized on a silica matrix was associated with the high ROS life time and with the presence of singlet oxygen, which contributes to the complete photomineralization of DCF.
Structural, Optical, Electrical, and Magnetic Properties of PVA:Gd3+ and PVA:Ho3+ Polymer Films
Authors: Reddy M. Obula , Chandra Babu B.
Published: May 2015

Polymer films of PVA:Gd3+ and PVA:Ho3+ have been synthesized by a solution casting method in order to study their structural, optical, electrical, and magnetic properties. The semicrystalline nature of the polymer films has been confirmed from XRD analysis. The FTIR analysis confirms the complex formation of the polymer with the metal ions. Dielectric studies of these films have also been carried out at various set temperatures in the frequency from 100 Hz to 1 MHz for carrying out impedance spectroscopy analysis to evaluate the electrical conductivity which arises due to a single conduction mechanism and thus to have a single semicircle pattern from these polymer films. The DC electrical conductivity increases with an increase in the temperature and it could be due to high mobility of free charges (polarons and free ions) at higher temperatures. The conductivity trend follows the Arrhenius equation for PVA:Gd3+ and for PVA:Ho3+ polymer films. PVA:Gd3+ polymer films show ferromagnetic nature, and PVA:Ho3+ polymer films have revealed paramagnetic nature based on the trends noticed in the magnetic characteristic profiles.
Adenomatoid Tumor of the Tunica Albuginea in a Boy: A Case Report and Literature Review
Authors: Guo Kaimin , Tian Runhui , Liu Lingyun , Du Congqi , Li Fubiao , Wang Hongliang
Published: May 2015

Adenomatoid tumors (AT) are the most common paratesticular neoplasms and account for approximately 30% of all paratesticular masses. Most of them occur in the third or fourth decade and present as well-defined firm and painless masses. We report here a case of adenomatoid tumor from tunica albuginea. This patient is a 12-year-old boy with left testicular pain for 6 months. Scrotal ultrasonography revealed a solid mass of paratesticular origin. The histology and immunohistochemistry confirmed the final diagnosis. A right tumor resection was performed. Because of its rarity, the clinical and histopathologic appearance is seldom illustrated. Here we present a case report and a comprehensive literature review with the objective of providing useful information on this entity.
Caries Experience Differs between Females and Males across Age Groups in Northern Appalachia
Authors: Shaffer John R. , Leslie Elizabeth J. , Feingold Eleanor , Govil Manika , McNeil Daniel W. , Crout Richard J. , Weyant Robert J. , Marazita Mary L.
Published: May 2015

Sex disparities in dental caries have been observed across many populations, with females typically exhibiting higher prevalence and more affected teeth. In this study we assessed the sex disparities in two Northern Appalachian populations from West Virginia (WV,N=1997) and Pennsylvania (PA,N=1080) by comparing caries indices between males and females across four phases of dental development: primary dentition in children aged 1–5 years, mixed dentition in children aged 6–11 years, permanent dentition in adolescents aged 12–17 years, and permanent dentition in adults aged 18–59 years. No significant sex differences were observed for children aged 1–5 years. Contrary to national and international trends, WV girls aged 6–11 years had 1.5 fewer affected teeth than boys(p<0.001). However, by ages 12–17, caries indices in the WV girls matched those in boys. In both WV and PA adults, women and men had similar total counts of affected teeth (i.e., DMFT), although women had more dental restorations(p<0.001)and men had more current decay(p<0.001). These results suggest that in some Appalachian populations, young girls benefit from protection against caries that is lost during adolescence and that adult women utilize dental health care to a greater degree than men.
Study on the Dynamic Biological Characteristics of Sca-1+Hematopoietic Stem and Progenitor Cell Senescence
Authors: Geng Shan , Mu Xin-Yi , Chen Xiong-Bin , Hou Ji-Ying , Jia Dao-Yong , Xu Chun-Yan , Wang Ya-Ping
Published: May 2015

The researches in the dynamic changes of the progress of HSCs aging are very limited and necessary. In this study, male C57BL/6 mice were divided into 5 groups by age. We found that the superoxide damage of HSPCs started to increase from the middle age (6 months old), with notably reduced antioxidation ability. In accordance with that, the senescence of HSPCs also started from the middle age, since the self-renewal and differentiation ability remarkably decreased, and senescence-associated markers SA-β-GAL increased in the 6-month-old and the older groups. Interestingly, the telomere length and telomerase activity increased to a certain degree in the 6-month-old group. It suggested an intrinsic spontaneous ability of HSPCs against aging. It may provide a theoretical and experimental foundation for better understanding the senescence progress of HSPCs. And the dynamic biological characteristics of HSPCs senescence may also contribute to the clinical optimal time for antiaging drug intervention.
Recommending High Utility Queries via Query-Reformulation Graph
Authors: Wang JianGuo , Huang Joshua Zhexue , Wu Dingming
Published: May 2015

Query recommendation is an essential part of modern search engine which aims at helping users find useful information. Existing query recommendation methods all focus on recommending similar queries to the users. However, the main problem of these similarity-based approaches is that even some very similar queries may return few or even no useful search results, while other less similar queries may return more useful search results, especially when the initial query does not reflect user’s search intent correctly. Therefore, we propose recommending high utility queries, that is, useful queries with more relevant documents, rather than similar ones. In this paper, we first construct a query-reformulation graph that consists of query nodes, satisfactory document nodes, and interruption node. Then, we apply an absorbing random walk on the query-reformulation graph and model the document utility with the transition probability from initial query to the satisfactory document. At last, we propagate the document utilities back to queries and rank candidate queries with their utilities for recommendation. Extensive experiments were conducted on real query logs, and the experimental results have shown that our method significantly outperformed the state-of-the-art methods in recommending high utility queries.
Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study
Authors: van Halsema Clare L. , Chihota Violet N. , Gey van Pittius Nicolaas C. , Fielding Katherine L. , Lewis James J. , van Helden Paul D. , Churchyard Gavin J. , Grant Alison D.
Published: May 2015

Background. The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population.Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively.Results. Of 232 individuals included (228 (98%) male, median age 44 years),M. gordonae(60 individuals),M. kansasii(50), andM. aviumcomplex (MAC: 38) were the commonest species. Of 38 MAC isolates, only 2 (5.3%) were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77%) among those tested. No differences were found in probability of death or medical separation by NTM species.Conclusions.M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment.
Electrophoretic Deposition of SnO2Nanoparticles and Its LPG Sensing Characteristics
Authors: Günkaya Göktuğ , Gürbüz Mevlüt , Doğan Aydın
Published: May 2015

HomogenizedSnO2nanoparticles (60 nm) in acetylacetone mediums, both with and without iodine, were deposited onto platinum coated alumina substrate and interdigital electrodes using the electrophoretic deposition (EPD) method for gas sensor applications. Homogeneous and porous film layers were processed and analyzed at various coating times and voltages. The structure of the deposited films was characterized by a scanning electron microscopy (SEM). The gas sensing properties of theSnO2films were investigated using liquid petroleum gas (LPG) for various lower explosive limits (LEL). The results showed that porous, crack-free, and homogeneousSnO2films were achieved for 5 and 15 sec at 100 and 150 V EPD parameters using an iodine-free acetylacetone basedSnO2suspension. The optimum sintering for the depositedSnO2nanoparticles was observed at 500°C for 5 min. The results showed that the sensitivity of the films was increased with the operating temperature. The coated films with EPD demonstrated a better sensitivity for the 20 LEL LPG concentrations at a 450°C operating temperature. The maximum sensitivity of theSnO2sensors at 450°C to 20 LEL LPG was 30.
MR-Guided Near-Infrared Spectral Tomography Increases Diagnostic Performance of Breast MRI
Authors: Mastanduno Michael A. , Xu Junqing , El-Ghussein Fadi , Jiang Shudong , Yin Hong , Zhao Yan , Wang Ke , Ren Fang , Gui Jiang , Pogue Brian W. , Paulsen Keith D.
Published: May 2015

Purpose: The purpose of this study was to determine the diagnostically most important molecular biomarkers quantified by magnetic resonance-guided (MR) near-infrared spectral tomography (NIRST) that distinguish malignant breast lesions from benign abnormalities when combined with outcomes from clinical breast MRI.

Experimental Design: The study was HIPAA compliant and approved by the Dartmouth Institutional Review Board, the NIH, the United States State Department, and Xijing Hospital. MR-guided NIRST evaluated hemoglobin, water, and lipid content in regions of interest defined by concurrent dynamic contrast-enhanced MRI (DCE-MRI) in the breast. MRI plus NIRST was performed in 44 subjects (median age, 46, age range, 20–81 years), 28 of whom had subsequent malignant pathologic diagnoses, and 16 had benign conditions. A subset of 30 subject examinations yielded optical data that met minimum sensitivity requirements to the suspicious lesion and were included in the analyses of diagnostic performance.

Results: In the subset of 30 subject examinations meeting minimum optical data sensitivity criterion, the MR-guided NIRST separated malignant from benign lesions using total hemoglobin (HbT; P < 0.01) and tissue optical index (TOI; P < 0.001). Combined MRI plus TOI data caused one false positive and 1 false negative, and produced the best diagnostic performance, yielding an AUC of 0.95, sensitivity of 95%, specificity of 89%, positive predictive value of 95%, and negative predictive value of 89%, respectively.

Conclusions: MRI plus NIRST results correlated well with histopathologic diagnoses and could provide additional information to reduce the number of MRI-directed biopsies. Clin Cancer Res; 21(17); 3906–12. ©2015 AACR.
Maintenance Treatment with Cetuximab and BAY86-9766 Increases Antitumor Efficacy of Irinotecan plus Cetuximab in Human Colorectal Cancer Xenograft Models
Authors: Troiani Teresa , Napolitano Stefania , Martini Giulia , Martinelli Erika , Cardone Claudia , Normanno Nicola , Vitagliano Donata , Morgillo Floriana , Fenizia Francesca , Lambiase Matilde , Formisano Luigi , Bianco Roberto , Ciardiello Davide , Ciardiello Fortunato
Published: May 2015

Purpose: The use of cetuximab in the treatment of metastatic colorectal cancer is limited by development of resistance.

Experimental Design: We have investigated in three models of highly epidermal growth factor receptor (EGFR)–dependent colorectal cancer xenografts, the effect of maintenance therapy with different kinase inhibitors alone or in combination with cetuximab, after cytotoxic treatment induction with irinotecan plus cetuximab.

Results: SW48, LIM 1215, and GEO colorectal cancer cell lines were engrafted into nude mice and treated for 3 weeks with irinotecan and/or cetuximab. The combined treatment induced a significant reduction of tumor size. A subsequent experiment was performed in all three xenograft models in which after an induction treatment with irinotecan plus cetuximab, mice were randomly assigned to one of the following treatments: control, cetuximab, regorafenib, a selective PIK3CA inhibitor (PIK3CAi), a selective MEK inhibitor (MEKi), and/or the combination of each inhibitor with cetuximab. The cetuximab plus MEKi treatment determined the best antitumor activity with suppression of tumor growth. This effect was prolonged for 13 to 15 weeks after cessation of therapy and was accompanied by prolonged survival. Antitumor activity was accompanied by inhibition of the MAPK and MEK pathways. Moreover, in the cetuximab plus MEKi-treated SW48 xenograft group, KRAS mutations as a mechanism of acquired resistance were detected in 25% of cases compared with 75% KRAS mutations in the MEKi-treated group.

Conclusions: A possible strategy to prevent and/or overcome resistance to anti-EGFR inhibitors in metastatic colorectal cancer is a maintenance therapy with cetuximab plus MEKi after an initial treatment with irinotecan plus cetuximab. Clin Cancer Res; 21(18); 4153–64. ©2015 AACR.
Association between Apolipoprotein E Variants and Obesity-Related Traits in Mexican School Children
Authors: Rodríguez-Carmona Yanelli , Pérez-Rodríguez Marcela , Gámez-Valdez Eli , López-Alavez Francisco J. , Hernández-Armenta Claudia I. , Vega-Monter Norma , Leyva-García Gerardo , Monge-Cázares Tulia , Barrera Valencia Daniela , Balderas Monroy Marisol , Pfeffer Frania , Meléndez Guillermo , Pérez Lizaur Ana Bertha , Pardío Jeanette , Tejero María Elizabeth
Published: May 2015

Background/Aim: Genetic variation in apolipoprotein E (ApoE) has a key role in lipid metabolism. However, its contribution to the amount and distribution of body fat is under investigation. The aim of this study was to analyze the association between genetic variation in ApoE and obesity-related traits in Mexican school children. Material and Methods: Anthropometric, body composition and physical activity measures were conducted using standard methods in 300 children (177 girls/123 boys) who fulfilled the inclusion criteria. DNA was isolated from saliva. ApoE genotypes were analyzed by allelic discrimination. The association between variation in ApoE and anthropometric and body composition measures was investigated using the General Linear Model. Results: The mean ± SD values for age, body mass index (BMI) and waist circumference (WC) were 9.05 ± 0.80 years, 19.01 ± 3.83 and 67.98 ± 10.97 cm, respectively. Approximately 46% of the participants were overweight or obese. A significant association between ApoE isoforms and WC was found after controlling for age, sex and the percentage of physical activity (p = 0.025). Significant main effects were found for vigorous physical activity and light physical activity influencing the adiposity-related BMI (p < 0.001) and WC (p = 0.044), respectively. Conclusions: Variation in ApoE and physical activity intensity were associated with adiposity-related phenotypes in Mexican school children.
Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium
Authors: Kinaan Mustafa , Ding Hong , Triggle Chris R.
Published: May 2015

The anti-diabetic and oral hypoglycaemic agent metformin, first used clinically in 1958, is today the first choice or ‘gold standard' drug for the treatment of type 2 diabetes and polycystic ovary disease. Of particular importance for the treatment of diabetes, metformin affords protection against diabetes-induced vascular disease. In addition, retrospective analyses suggest that treatment with metformin provides therapeutic benefits to patients with several forms of cancer. Despite almost 60 years of clinical use, the precise cellular mode(s) of action of metformin remains controversial. A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK. Discrepancies, however, between the concentrations of metformin used in in vitro studies versus therapeutic levels suggest that caution should be applied before extending inferences derived from cell-based studies to therapeutic benefits seen in patients. Conceivably, the effects, or some of them, may be at least partially independent of AMPK and/or mitochondrial respiration and reflect a direct effect of either metformin or a minor and, as yet, unidentified putative metabolite of metformin on a target protein(s)/signalling cascade. In this review, we critically evaluate the data from studies that have investigated the pharmacokinetic properties and the cellular and clinical basis for the oral hypoglycaemic, insulin-sensitising and vascular protective effects of metformin.
Antinociceptive Efficacy of Retigabine in the Monosodium Lodoacetate Rat Model for Osteoarthritis Pain
Authors: Li Han , Wang Fei , Wang Xiaofeng , Sun Ran , Chen Jingqing , Chen Baicheng , Zhang Yingze
Published: May 2015

Background: The goal of pharmacological osteoarthritis (OA) treatments is to reduce pain and thus increase patient joint function and quality of life. Retigabine, a potent Kv7/M channel activator, shows analgesic efficacy in animal models of chronic inflammatory and neuropathic pain. We hypothesized that retigabine may also mitigate OA pain. To determine the effects of retigabine on pain behavior associated with monosodium iodoacetate (MIA)-induced OA. Methods: The OA model was established with an intra-articular injection of MIA through the right patellar ligament, animals were treated with retigabine, and pain-related behaviors were assessed. Results: Retigabine significantly increased the mechanical threshold and prolonged the withdrawal latency of OA rats at 3-14 days. Retigabine also increased the mechanical threshold and prolonged the withdrawal latency of OA pain in a dose-dependent manner, with the strongest antinociceptive effect occurring at 60 min. The antinociceptive effects of retigabine were fully antagonized by the Kv7/M channel blocker XE991. Conclusion: Retigabine showed antinociceptive effects for OA pain in the MIA model at different times during pain development. Retigabine may be an alternative therapeutic treatment for OA.
Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study
Authors: Engelmann Beatrice , Bischof Julia , Dirk Anne-Luise , Friedrich Nele , Hammer Elke , Thiele Thomas , Führer Dagmar , Homuth Georg , Brabant Georg , Völker Uwe
Published: May 2015

Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT4 levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT4, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.
Kinect-Based Five-Times-Sit-to-Stand Test for Clinical and In-Home Assessment of Fall Risk in Older People
Authors: Ejupi Andreas , Brodie Matthew , Gschwind Yves J. , Lord Stephen R. , Zagler Wolfgang L. , Delbaere Kim
Published: May 2015

Background: Accidental falls remain an important problem in older people. The five-times-sit-to-stand (5STS) test is commonly used as a functional test to assess fall risk. Recent advances in sensor technologies hold great promise for more objective and accurate assessments. Objective: The aims of this study were: (1) to examine the feasibility of a low-cost and portable Kinect-based 5STS test to discriminate between fallers and nonfallers and (2) to investigate whether this test can be used for supervised clinical, supervised and unsupervised in-home fall risk assessments. Methods: A total of 94 community-dwelling older adults were assessed by the Kinect-based 5STS test in the laboratory and 20 participants were tested in their own homes. An algorithm was developed to automatically calculate timing- and speed-related measurements from the Kinect-based sensor data to discriminate between fallers and nonfallers. The associations of these measurements with standard clinical fall risk tests and the results of supervised and unsupervised in-home assessments were examined. Results: Fallers were significantly slower than nonfallers on Kinect-based measures. The mean velocity of the sit-to-stand transitions discriminated well between the fallers and nonfallers based on 12-month retrospective fall data. The Kinect-based measures collected in the laboratory correlated strongly with those collected in the supervised (r = 0.704-0.832) and unsupervised (r = 0.775-0.931) in-home assessments. Conclusion: In summary, we found that the Kinect-based 5STS test discriminated well between the fallers and nonfallers and was feasible to administer in clinical and supervised in-home settings. This test may be useful in clinical settings for identifying high-risk fallers for further intervention or for regular in-home assessments in the future.
Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs
Authors: Zhuang Zaishou , Tang Mengmeng , Zheng Yangming , Hu Lufeng , Lin Feiyan
Published: May 2015

Background: Dimethoate (DM), one of the most widely used systemic organophosphate insecticide, has been reported to exert toxic effects after long-time subchronic exposure. This study aims at investigating the toxic effect of DM on liver after repeated administration of low doses of DM in rats. Methods: Twenty Sprague-Dawley rats were randomly divided into the control group (n = 10) and the DM group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were evaluated by the Cocktail method. Results: The level of AChE (acetylcholinesterase) was significantly decreased, hepatic functions were damaged and the mRNA level of CYP2D1 was significantly increased in the DM group (p < 0.05). The pharmacokinetics of probe drug revealed AUC(0-t), AUC(0-∞), t1/2 and Cmax of metoprolol was shorten in the DM group (p < 0.05). However, there were no statistical differences in MRT, t1/2, CL and Tmax for phenacetin, tolbutamide and midazolam. Conclusions: A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks.
Computer-Aided Diagnosis of Depression Using EEG Signals
Authors: Acharya U. Rajendra , Sudarshan Vidya K. , Adeli Hojjat , Santhosh Jayasree , Koh Joel E.W. , Adeli Amir
Published: May 2015

The complex, nonlinear and non-stationary electroencephalogram (EEG) signals are very tedious to interpret visually and highly difficult to extract the significant features from them. The linear and nonlinear methods are effective in identifying the changes in EEG signals for the detection of depression. Linear methods do not exhibit the complex dynamical variations in the EEG signals. Hence, chaos theory and nonlinear dynamic methods are widely used in extracting the EEG signal features for computer-aided diagnosis (CAD) of depression. Hence, this article presents the recent efforts on CAD of depression using EEG signals with a focus on using nonlinear methods. Such a CAD system is simple to use and may be used by the clinicians as a tool to confirm their diagnosis. It should be of a particular value to enable the early detection of depression.
Short Children with CHARGE Syndrome: Do They Benefit from Growth Hormone Therapy?
Authors: Dörr Helmuth G. , Boguszewski Margaret , Dahlgren Jovanna , Dunger David , Geffner Mitchell E. , Hokken-Koelega Anita C. , Lindberg Anders , Polak Michel , Rooman Raoul ,   on behalf of KIGS International Board
Published: May 2015

Aim: The aim of this study was to evaluate the response to recombinant growth hormone (GH) treatment in short children with CHARGE syndrome. Patients: We identified 51 children (28 boys and 23 girls) in KIGS (Pfizer International Growth Database). The median chronological age was 7.6 years at the start of GH therapy and 13.2 years at the latest visit. Evaluation for GH deficiency (n = 33) was based on the following: peak GH level 7.3 μg/l and IGF-I level -2.01 standard deviation score (SDS). Sixteen subjects (9 boys) were followed longitudinally for 2 years. Results: Birth length (median SDS, -0.47) and weight (-0.97) were slightly reduced. At the start of GH therapy, height was -3.6 SDS, BMI -0.7 SDS, and the GH dose was 0.26 mg/kg/week. At the latest visit after 2.7 years of GH therapy, height had increased to -2.2 SDS and BMI to -0.5 SDS. In the longitudinal group, height increased from -3.72 SDS at the start of GH therapy to -2.92 SDS after 1 year to -2.37 SDS after 2 years of therapy (start - 2 years: p < 0.05), height velocity increased from -1.69 to 2.98 to 0.95 SDS, and BMI and GH dose (mg/kg/week) remained almost unchanged. Conclusions: Our data show a positive effect of conventional doses of GH on short-term growth velocity for the longitudinal as well as for the total group, without any safety issues.
Modulation of Clr Ligand Expression and NKR-P1 Receptor Function during Murine Cytomegalovirus Infection
Authors: Aguilar Oscar A. , Mesci Aruz , Ma Jaehun , Chen Peter , Kirkham Christina L. , Hundrieser Joachim , Voigt Sebastian , Allan David S.J. , Carlyle James R.
Published: May 2015

Viruses are known to induce pathological cellular states that render infected cells susceptible or resistant to immune recognition. Here, we characterize an MHC-I-independent natural killer (NK) cell recognition mechanism that involves modulation of inhibitory NKR-P1B:Clr-b receptor-ligand interactions in response to mouse cytomegalovirus (MCMV) infection. We demonstrate that mouse Clr-b expression on healthy cells is rapidly lost at the cell surface and transcript levels in a time- and dose-dependent manner upon MCMV infection. In addition, cross-species infections using rat cytomegalovirus (RCMV) infection of mouse fibroblasts and MCMV infection of rat fibroblasts suggest that this response is conserved during host-pathogen interactions. Active viral infection appears to be necessary for Clr-b loss, as cellular stimulation using UV-inactivated whole virus or agonists of many innate pattern recognition receptors failed to elicit efficient Clr-b downregulation. Notably, Clr-b loss could be partially blocked by titrated cycloheximide treatment, suggesting that early viral or nascent host proteins are required for Clr-b downregulation. Interestingly, reporter cell assays suggest that MCMV may encode a novel Clr-b-independent immunoevasin that functionally engages the NKR-P1B receptor. Together, these data suggest that Clr-b modulation is a conserved innate host cell response to virus infection that is subverted by multiple CMV immune evasion strategies.
Sebum Secretion of the Trunk and the Development of Truncal Acne in Women: Do Truncal Acne and Sebum Affect Each Other?
Authors: Kim Bo Ri , Chun Mi Young , Kim Sung Ae , Youn Sang Woong
Published: May 2015

Background: There are few published data on truncal acne because most studies have focused on facial acne. Aims: The objective of this study was to investigate truncal sebum secretion levels in patients with acne vulgaris and to evaluate the relationship between sebum secretion and the development of acne lesions. Methods: The sebum casual levels at five different facial sites and ten truncal sites were measured in 35 Korean females with acne using a Sebumeter®. We performed an analysis of the correlation between sebum excretion and acne lesion number. Results: We found that all of the truncal sites analyzed had lower sebum secretion levels than the facial sites. There was no significant correlation between sebum secretion and acne lesions on the trunk. Conclusion: Pathogenic factors other than sebum may have a predominant role in the development of truncal acne.
Do We Need Tailored Smoking Cessation Interventions for Smokers with COPD? A Comparative Study of Smokers with and without COPD Regarding Factors Associated with Tobacco Smoking
Authors: van Eerd Eva A.M. , van Rossem Carolien R. , Spigt Mark G. , Wesseling Geertjan , van Schayck Onno C.P. , Kotz Daniel
Published: May 2015

Background: The prevalence of tobacco smoking in patients with chronic obstructive pulmonary disease (COPD) is high. It is assumed that this group of smokers has more difficulties quitting than smokers without COPD. In order to increase the effectiveness of smoking cessation treatments in smokers with COPD it is important to identify any smoking-related factors which are specific to this group of smokers. Objective: To compare smokers with COPD with smokers without COPD regarding factors associated with tobacco smoking and quitting. Methods: We conducted a questionnaire survey in all smoking patients with a recorded diagnosis of COPD from a large Dutch primary health care network. We compared this group with twice as many age-, sex- and health care centre-matched smokers without COPD. Results: Respondents were 107 smokers with COPD and 86 smokers without COPD. The number of attempts to quit was similar in both groups but more smokers with COPD had ever used pharmacological, behavioural and alternative smoking cessation treatments. Furthermore, smokers with COPD more often received triggers to quit from their environment and from their general practitioner, and they were more concerned about, and aware of, the health risks of smoking. Importantly, smokers with COPD reported higher levels of depression and cigarette dependence and a lower self-efficacy to refrain from smoking than smokers without COPD. Conclusion: Smokers with COPD differ from smokers without COPD on several factors which are associated with tobacco smoking and quitting. Taking into account these differences may help to increase the effectiveness of smoking cessation treatments for the specific group of smokers with COPD.