bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Effects of Culture Substrates on Human Pluripotent Stem Cells
Authors: Hayashi Yohei , Furue Miho Kusuda
Published: August 2016

In recent years, as human pluripotent stem cells (hPSCs) have been commonly cultured in feeder‐free conditions, a number of cell culture substrates have been applied or developed. However, the functional roles of these substrates in maintaining hPSC self‐renewal remain unclear. Here in this review, we summarize the types of these substrates and their effect on maintaining hPSC self‐renewal. Endogenous extracellular matrix (ECM) protein expression has been shown to be crucial in maintaining hPSC self‐renewal. These ECM molecules interact with integrin cell‐surface receptors and transmit their cellular signaling. We discuss the possible effect of integrin‐mediated signaling pathways on maintaining hPSC self‐renewal. Activation of integrin‐linked kinase (ILK), which transmits ECM‐integrin signaling to AKT (also known as protein kinase B), has been shown to be critical in maintaining hPSC self‐renewal. Also, since naïve pluripotency has been widely recognized as an alternative pluripotent state of hPSCs, we discuss the possible effects of culture substrates and integrin signaling on naïve hPSCs based on the studies of mouse embryonic stem cells. Understanding the role of culture substrates in hPSC self‐renewal and differentiation enables us to control hPSC behavior precisely and to establish scalable or microfabricated culture technologies for regenerative medicine and drug development.
Improved Efficiency and Reliability of NGS Amplicon Sequencing Data Analysis for Genetic Diagnostic Procedures Using AGSA Software
Authors: Poulet Axel , Privat Maud , Ponelle Flora , Viala Sandrine , Decousus Stephanie , Perin Axel , Lafarge Laurence , Ollier Marie , El Saghir Nagi S. , Uhrhammer Nancy , Bignon Yves-Jean , Bidet Yannick
Published: August 2016

Screening forBRCAmutations in women with familial risk of breast or ovarian cancer is an ideal situation for high-throughput sequencing, providing large amounts of low cost data. However, 454, Roche, and Ion Torrent, Thermo Fisher, technologies produce homopolymer-associated indel errors, complicating their use in routine diagnostics. We developed software, named AGSA, which helps to detect false positive mutations in homopolymeric sequences. Seventy-two familial breast cancer cases were analysed in parallel by amplicon 454 pyrosequencing and Sanger dideoxy sequencing for genetic variations of theBRCAgenes. All 565 variants detected by dideoxy sequencing were also detected by pyrosequencing. Furthermore, pyrosequencing detected 42 variants that were missed with Sanger technique. Six amplicons contained homopolymer tracts in the coding sequence that were systematically misread by the software supplied by Roche. Read data plotted as histograms by AGSA software aided the analysis considerably and allowed validation of the majority of homopolymers. As an optimisation, additional 250 patients were analysed using microfluidic amplification of regions of interest (Access Array Fluidigm) of the BRCA genes, followed by 454 sequencing and AGSA analysis. AGSA complements a complete line of high-throughput diagnostic sequence analysis, reducing time and costs while increasing reliability, notably for homopolymer tracts.
Behavioral Problems in Juvenile Idiopathic Arthritis: A Controlled Study to Examine the Risk of Psychopathology in a Chronic Pediatric Disorder
Authors: Memari Amir Hossein , Chamanara Elham , Ziaee Vahid , Kordi Ramin , Raeeskarami Seyed-Reza
Published: August 2016

Children with juvenile idiopathic arthritis (JIA) are prone to the problems that can delay their psychosocial development; however, the existing literature has not reached a consensus on the psychological problems related to JIA. A total of 51 children and adolescents with JIA and 75 healthy controls aged 6 to 18 years were examined using the Child Behavioral Checklist (CBCL). Our results represented that 70 percent of JIA group reached “borderline clinical” range or “clinical” range in internalizing problems, while this percentage in the control group was 18 percent. In addition, our results indicated that JIA group has gotten significantly higher scores (more than twofold) in externalizing behaviors compared to control group. Furthermore, children with JIA showed higher rate of anxiety/depression, withdrawal/depression, somatic complaints, rule breaking behaviors, and aggressive behaviors as well as thought and social problems compared to control group (p<0.001). As a conclusion, children and adolescents with JIA compared to healthy controls may show higher rate of both internalizing and externalizing problems. Furthermore, our novel findings on externalizing, social, and thought problems in JIA warrant further investigation on affected children who may be at greater risk of future psychopathologies.
Stress Recovery Effects of High- and Low-Frequency Amplified Music on Heart Rate Variability
Authors: Nakajima Yoshie , Tanaka Naofumi , Mima Tatsuya , Izumi Shin-Ichi
Published: August 2016

Sounds can induce autonomic responses in listeners. However, the modulatory effect of specific frequency components of music is not fully understood. Here, we examined the role of the frequency component of music on autonomic responses. Specifically, we presented music that had been amplified in the high- or low-frequency domains. Twelve healthy women listened to white noise, a stress-inducing noise, and then one of three versions of a piece of music: original, low-, or high-frequency amplified. To measure autonomic response, we calculated the high-frequency normalized unit (HFnu), low-frequency normalized unit, and the LF/HF ratio from the heart rate using electrocardiography. We defined the stress recovery ratio as the value obtained after participants listened to music following scratching noise, normalized by the value obtained after participants listened to white noise after the stress noise, in terms of the HFnu, low-frequency normalized unit, LF/HF ratio, and heart rate. Results indicated that high-frequency amplified music had the highest HFnu of the three versions. The stress recovery ratio of HFnu under the high-frequency amplified stimulus was significantly larger than that under the low-frequency stimulus. Our results suggest that the high-frequency component of music plays a greater role in stress relief than low-frequency components.
Data Acquisition System for In Situ Monitoring of Chemoelectrical Potential in Living Plant Fuel Cells
Authors: Chee Fuei Pien , Chen Cheng Ann , Chang Jackson Hian Wui , Choo Ying Ying , Dayou Jedol
Published: August 2016

Photosynthesis process in plants generates numerous sources of bioenergy. However, only a small fraction is readily exploited for electrical energy. The impact of environmental factors is one of the significant physiological influences on the electrical potential of the plants. Hence, we developed a data acquisition (DAQ) system for instantaneous monitoring of electrical potential in plants and Aloe vera was used as a plant sample. The static response characterization, capability index (P/T), and Pearson’s coefficient of correlation procedures were applied to assess the reliability of the obtained data. This developed system offers the capability of in situ monitoring and detecting gradual changes in the electrical potential of plants up to a correlational strength of greater than 0.7. Interpretation of the electrical signal mechanisms in the Aloe vera plant and the optimization of the electricity can be achieved through the application of this monitoring system. This system, therefore, can serve as a tool to measure and analyze the electrical signals in plants at different conditions.
Perspectives on the Role and Synergies of Architecture and Social and Built Environment in Enabling Active Healthy Aging
Authors: Chrysikou Evangelia , Rabnett Richard , Tziraki Chariklia
Published: August 2016

Research has demonstrated that enabling societal and physical infrastructure and personal accommodations enhance healthy and active aging throughout the lifespan. Yet, there is a paucity of research on how to bring together the various disciplines involved in a multidomain synergistic collaboration to create new living environments for aging. This paper aims to explore the key domains of skills and knowledge that need to be considered for a conceptual prototype of an enabling educational process and environments where healthcare professionals, architects, planners, and entrepreneurs may establish a shared theoretical and experiential knowledge base, vocabulary, and implementation strategies, for the creation of the next generation of living communities of active healthy adults, for persons with disabilities and chronic disease conditions. We focus on synergistic, paradigmatic, simple, and practical issues that can be easily upscaled through market mechanisms. This practical and physically concrete approach may also become linked with more elaborate neuroscientific and technologically sophisticated interventions. We examine the domains of knowledge to be included in establishing a learning model that focuses on the still-understudied impact of the benefits toward active and healthy aging, where architects, urban planners, clinicians, and healthcare facility managers are educated toward a synergistic approach at the operational level.
Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis
Authors: Tantiyavarong Pichaya , Traitanon Opas , Chuengsaman Piyatida , Patumanond Jayanton , Tasanarong Adis
Published: August 2016

Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment.Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis.Results. There were 644 episodes in 455 patients: 378 (58.7%) of early response, 122 (18.9%) of delayed response, and 144 (22.3%) of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (pvalue < 0.001 for all comparisons).Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter.
Characterizations of Fuzzy Ideals in Coresiduated Lattices
Authors: Liu Yan , Zheng Mucong
Published: August 2016

The notions of fuzzy ideals are introduced in coresiduated lattices. The characterizations of fuzzy ideals, fuzzy prime ideals, and fuzzy strong prime ideals in coresiduated lattices are investigated and the relations between ideals and fuzzy ideals are established. Moreover, the equivalence of fuzzy prime ideals and fuzzy strong prime ideals is proved in prelinear coresiduated lattices. Furthermore, the conditions under which a fuzzy prime ideal is derived from a fuzzy ideal are presented in prelinear coresiduated lattices.
Unusual Closed Traumatic Avulsion of Both Flexor Tendons in Zones 1 and 3 of the Little Finger
Authors: Soro Marie-Aimée Päivi , Christen Thierry , Durand Sébastien
Published: August 2016

Closed tendon avulsion of both flexor tendons in the same finger is an extremely rare condition. We encountered the case of a patient who presented a rupture of the flexor digitorum profundus in zone 1 and flexor digitorum superficialis in zone 3 in the little finger. This occurrence has not been reported previously. We hereby present our case, make a review of the literature of avulsion of both flexor tendons of the same finger, and propose a treatment according to the site of the ruptures.
Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment
Authors: Markeb Ahmed A. , El-Maali Nagwa A. , Sayed Douaa M. , Osama Amany , Abdel-Malek Mohamed A. Y. , Zaki Amen H. , Elwanis Mostafa E. A. , Driscoll James J.
Published: August 2016

Purpose. The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells.Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry.Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone.Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis
Authors: Washington Samuel , Osterberg E. Charles , Elliott Sean P. , Hittelman Adam B. , Breyer Benjamin N.
Published: August 2016

We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting.
An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms
Authors: Hua Hong-Li , Zhang Fa-Zhan , Labena Abraham Alemayehu , Dong Chuan , Jin Yan-Ting , Guo Feng-Biao
Published: August 2016

Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset fromSynechococcus elongatus, which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge.
Symptomatic Bilateral Torn Discoid Medial Meniscus Treated with Saucerization and Suture
Authors: Sevillano-Perez Enrique , Espejo-Reina Alejandro , Espejo-Reina María Josefa
Published: August 2016

Discoid meniscus is an anatomical congenital anomaly more often found in the lateral meniscus. A discoid medial meniscus is a very rare anomaly, and even more rare is to diagnose a bilateral discoid medial meniscus although the real prevalence of this situation is unknown because not all the discoid medial menisci are symptomatic and if the contralateral knee is not symptomatic then it is not usually studied. The standard treatment of this kind of pathology is partial meniscectomy. Currently the tendency is to be very conservative so suture and saucerization of a torn discoid meniscus when possible are gaining support. We present the case of a 13-year-old patient who was diagnosed with symptomatic torn bilateral discoid medial meniscus treated by suturing the tear and saucerization. To the best of our knowledge this is the first case reported of bilateral torn discoid medial meniscus treated in this manner in the same patient.
Predictors of Treatment Outcome for Retreatment Pulmonary Tuberculosis Cases among Tribal People of an Eastern India District: A Prospective Cohort Study
Authors: Saha Rajib
Published: August 2016

Objective. The study was conducted to assess the treatment outcome of different category retreatment cases with the aim of finding out the important predictors of unfavorable outcomes.Methodology. This hospital based prospective cohort study was conducted in three tuberculosis units (TUs) of west Midnapore (a district of Eastern India), covering mostly the tribal populated areas. Patients who were registered for Category II antituberculosis treatment between 1st quarter of 2013 (Jan to Mar) and 4th quarter of 2013 (Oct to Dec) were considered as our study cohort and they were followed up till December 2014. The study was started with 177 patients but ultimately ended with 165 patients.Results. Unfavorable outcome was observed among 24.8% patients. Among them mostly 51.2% were defaulter, 22% were failure case, and 26.8% died during treatment. Patients, who were minority by religion, were found 4 times more vulnerable for unfavorable outcome. Unfavorable outcome was found 7 times more common among retreatment TB cases who remain sputum positive after completion of initiation phase of Category II treatment.Conclusion. Programmatic approach should be specified to address the minority by religion population and to reduce the load of sputum positive cases after completion of initiation phase treatment by tracking them.
Effect of Hydroxychloroquine on the Retinal Layers: A Quantitative Evaluation with Spectral-Domain Optical Coherence Tomography
Authors: Uslu Hasim , Gurler Bulent , Yildirim Aydin , Tatar Mehmet Gurkan , Aylin Kantarcı Feride , Goker Hasan , Pehlevan Hatice Seval , Colak Hatice Nur
Published: August 2016

Purpose.To evaluate the effect of hydroxychloroquine on retinal pigment epithelium- (RPE-) Bruch’s membrane complex, photoreceptor outer segment, and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses using spectral-domain optical coherence tomography (SD-OCT).Methods.In this prospective case-control study, 51 eyes of 51 hydroxychloroquine patients and 30 eyes of 30 healthy subjects were included. High-quality images were obtained using a Cirrus HD-OCT with 5-line raster mode; the photoreceptor inner segment (IS) and outer segment (OS), sum of the segments (IS + OS), and RPE-Bruch’s membrane complex were analyzed.Results.The thicknesses of the IS + OS and OS layers were significantly lower in the hydroxychloroquine subjects compared to the control subjects (P<0.05). RPE-Bruch’s membrane complex thicknesses were significantly higher in the hydroxychloroquine subjects than for those of the control subjects (P<0.05). The minimum and temporal-inferior macular GCIPL thicknesses were significantly different between the patients with hydroxychloroquine use and the control subjects (P=0.04andP=0.03, resp.).Conclusions.The foveal photoreceptor OS thinning, loss of GCIPL, and RPE-Bruch’s membrane thickening were detected in patients with hydroxychloroquine therapy. This quantitative approach using SD-OCT images may have important implications to use as an early indicator of retinal toxicity without any visible signs of hydroxychloroquine retinopathy.
Method of Fusion Diagnosis for Dam Service Status Based on Joint Distribution Function of Multiple Points
Authors: Jiang Zhenxiang , He Jinping
Published: August 2016

The traditional methods of diagnosing dam service status are always suitable for single measuring point. These methods also reflect the local status of dams without merging multisource data effectively, which is not suitable for diagnosing overall service. This study proposes a new method involving multiple points to diagnose dam service status based on joint distribution function. The function, including monitoring data of multiple points, can be established with t-copula function. Therefore, the possibility, which is an important fusing value in different measuring combinations, can be calculated, and the corresponding diagnosing criterion is established with typical small probability theory. Engineering case study indicates that the fusion diagnosis method can be conducted in real time and the abnormal point can be detected, thereby providing a new early warning method for engineering safety.
Fracture Resistance of Endodontically Treated Maxillary Premolars Restored by Various Direct Filling Materials: An In Vitro Study
Authors: Mincik Jozef , Urban Daniel , Timkova Silvia , Urban Renata
Published: August 2016

The aim of this study is to compare the effect of various restorative materials on fracture resistance in maxillary premolars. Premolars (n=64) with no restorations or cracks were selected. MOD cavities were prepared considering the buccolingual width to be equal to half of the intercuspal distance. The specimens were randomly divided into 8 groups, 8 specimens each:group Aintact teeth,group Bunfilled cavity,group Ccomposite made by oblique layering technique,group Dcomposite with 2 mm cusp coverage,group Ebulk-filled posterior composite,group Fglass-ionomer,group Gamalgam, andgroup Hcomposite with proximal boxes. The specimens were subjected to an axial compression load with the mean values of fracture resistance in group A: 1289 N, group B: 181.75 N, group C: 445.38 N, group D: 645.88 N, group E: 355.13 N, group F: 352.00 N, group G: 191.38 N, and group H: 572.00 N. There was no significant difference between groups B and G, between C and D, E, and F, and between group D and H. All other measurements were statistically significant. We conclude that composite restoration with cusp coverage is the most ideal nonprosthetic solution for endodontically treated teeth. Cusp coverage increases the fracture resistance compared to the conventional cavity design.
PEDOT:PSS-Containing Nanohydroxyapatite/Chitosan Conductive Bionanocomposite Scaffold: Fabrication and Evaluation
Authors: Lari Alireza , Sun Tao , Sultana Naznin
Published: August 2016

Conductive poly(3,4-ethylenedioxythiophene)-poly(4-styrene sulfonate) (PEDOT:PSS) was incorporated into nanohydroxyapatite/chitosan (nHA/CS) composite scaffolds through a freezing and lyophilization technique. The bionanocomposite conductive scaffold was then characterized using several techniques. A scanning electron microscope image showed that the nHA and PEDOT:PSS were dispersed homogeneously in the chitosan matrix, which was also confirmed by energy-dispersive X-ray (EDX) analysis. The conductive properties were measured using a digital multimeter. The weight loss and water-uptake properties of the bionanocomposite scaffolds were studiedin vitro. Anin vitrocell cytotoxicity test was carried out using mouse fibroblast (L929) cells cultured onto the scaffolds. Using a freezing and lyophilization technique, it was possible to fabricate three-dimensional, highly porous, and interconnected PEDOT:PSS/nHA/CS scaffolds with good handling properties. The porosity was 74% and the scaffold’s conductivity was9.72±0.78 μS. The surface roughness was increased with the incorporation of nHA and PEDOT:PSS into the CS scaffold. The compressive mechanical properties increased significantly with the incorporation of nHA but did not change significantly with the incorporation of PEDOT:PSS. The PEDOT:PSS-containing nHA/CS scaffold exhibited significantly higher cell attachment. The PEDOT:PSS/nHA/CS scaffold could be a potential bionanocomposite conductive scaffold for tissue engineering.
Tympanosclerosis Presenting as Mass: Workup and Differential
Authors: Barry Jonnae Y. , Reghunathan Saranya , Jacob Abraham
Published: August 2016

Introduction. Tympanosclerosis is a commonly encountered entity within ENT clinics and primary care settings. Recognizing ear pathology is essential for correct management. Oftentimes the diagnosis is clear; however in certain cases further workup to rule out other more insidious disease processes is warranted.Case Report. We present a case of tympanosclerosis which presented as an ear mass without classic appearance of tympanosclerosis. Through imaging and biopsy the diagnosis of tympanosclerosis was made. The patient was treated surgically with good outcome.Discussion. Various ear pathologies, with different treatment algorithms, may present as clinically similar to one another. Differential diagnosis for this case included tympanosclerosis, cholesteatoma, or other middle ear masses. We review these entities and discuss their pathophysiology and implications on management.
Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease
Authors: Bryan Phillips-Farfán , Karla Carvajal , Edgar Alejandro Medina-Torres , Sara Elva Espinosa-Padilla , Gemma Fabrias , Luz Camacho
Published: August 2016

Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed.
ABBV-399, a c-Met Antibody–Drug Conjugate that Targets Both MET–Amplified and c-Met–Overexpressing Tumors, Irrespective of MET Pathway Dependence
Authors: Wang Jieyi , Anderson Mark G. , Oleksijew Anatol , Vaidya Kedar S. , Boghaert Erwin R. , Tucker Lora , Zhang Qian , Han Edward K. , Palma Joann P. , Naumovski Louie , Reilly Edward B.
Published: August 2016

Purpose: Despite the importance of the MET oncogene in many malignancies, clinical strategies targeting c-Met have benefitted only small subsets of patients with tumors driven by signaling through the c-Met pathway, thereby necessitating selection of patients with MET amplification and/or c-Met activation most likely to respond. An ADC targeting c-Met could overcome these limitations with potential as a broad-acting therapeutic.

Experimental Design: ADC ABBV-399 was generated with the c-Met–targeting antibody, ABT-700. Antitumor activity was evaluated in cancer cells with overexpressed c-Met or amplified MET and in xenografts including patient-derived xenograft (PDX) models and those refractory to other c-Met inhibitors. The correlation between c-Met expression and sensitivity to ABBV-399 in tumor and normal cell lines was assessed to evaluate the risk of on-target toxicity.

Results: A threshold level of c-Met expressed by sensitive tumor but not normal cells is required for significant ABBV-399–mediated killing of tumor cells. Activity extends to c-Met or amplified MET cell line and PDX models where significant tumor growth inhibition and regressions are observed. ABBV-399 inhibits growth of xenograft tumors refractory to other c-Met inhibitors and provides significant therapeutic benefit in combination with standard-of-care chemotherapy.

Conclusions: ABBV-399 represents a novel therapeutic strategy to deliver a potent cytotoxin to c-Met–overexpressing tumor cells enabling cell killing regardless of reliance on MET signaling. ABBV-399 has progressed to a phase I study where it has been well tolerated and has produced objective responses in c-Met–expressing non–small cell lung cancer (NSCLC) patients. Clin Cancer Res; 23(4); 992–1000. ©2016 AACR.
Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept
Authors: Peyrode Caroline , Weber Valérie , Voissière Aurélien , Maisonial-Besset Aurélie , Vidal Aurélien , Auzeloux Philippe , Gaumet Vincent , Borel Michèle , Dauplat Marie-Mélanie , Quintana Mercedes , Degoul Françoise , Rédini Françoise , Chezal Jean-Michel , Miot-Noirault Elisabeth
Published: August 2016

To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosarcoma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [3H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99mTc-NTP 15-5 scintigraphic imaging of PGs, 1H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the tolerability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma. Mol Cancer Ther; 15(11); 2575–85. ©2016 AACR.
Stem Cell-Mediated Regeneration of the Adult Brain
Authors: Jessberger Sebastian
Published: August 2016

Acute or chronic injury of the adult mammalian brain is often associated with persistent functional deficits as its potential for regeneration and capacity to rebuild lost neural structures is limited. However, the discovery that neural stem cells (NSCs) persist throughout life in discrete regions of the brain, novel approaches to induce the formation of neuronal and glial cells, and recently developed strategies to generate tissue for exogenous cell replacement strategies opened novel perspectives how to regenerate the adult brain. Here, we will review recently developed approaches for brain repair and discuss future perspectives that may eventually allow for developing novel treatment strategies in acute and chronic brain injury.
Comorbidities, Hospitalization, and Living Status of Dialysis Patients Over 80 Years
Authors: Leimbach Til , Kron Joachim , Pommer Wolfgang , Urbach Birgit , Kron Susanne
Published: August 2016

Background: An increasing number of patients start dialysis when they are over 80 years or reaches their eighties on dialysis. The burden of dialysis can affect their quality of life. Methods: Clinical and social data of all patients aged 80 years or older who underwent chronic dialysis treatment in a single center were analyzed. Results: Fifty-nine patients aged between 80 and 92 years were in chronic dialysis treatment on December 31, 2015. Median time on dialysis was 57 months (3-330 months). Hospitalization rate and days in hospital were lower in this group than in younger patients (1.05 vs. 1.34 hospitalizations; 8.3 vs. 9.0 hospital days per patient and year) despite the presence of many comorbidities. The median patency of the currently used arteriovenous shunt was 70 months (6-194 months). Social status was comparable with the population of the rest of the same average age range. Conclusion: Dialysis patients aged ≥80 years have a satisfactory quality of life with no more complications than younger patients.
A Systematic Review of the Definitions of Vascular Cognitive Impairment, No Dementia in Cohort Studies
Authors: Harrison Stephanie L. , Tang Eugene Y.H. , Keage Hannah A.D. , Taylor John-Paul , Allan Louise , Robinson Louise , Jagger Carol , Rockwood Kenneth , Stephan Blossom C.M.
Published: August 2016

Background/Aims: No set operational criteria for vascular cognitive impairment, no dementia (VCI-ND) have yet been established. The aim of this study is to undertake a systematic review to compare definitions of VCI-ND that have been used in cohort studies. Methods: Medline, PsycINFO and Embase were searched from inception to October 13, 2015. Initially, 3,142 records were screened, and 30 were included in this review. Results: No single set of criteria for defining VCI-ND was identified. VCI-ND was broadly defined as an absence of dementia, cognitive impairment in at least one cognitive domain with signs of vascular involvement, and intact activities of daily living. Conclusion: Defining criteria will enable individuals with VCI-ND to be efficiently compared across cohort studies to more accurately determine the prevalence and risk of dementia.
Oral Drugs Related with Muscle Wasting and Sarcopenia. A Review
Authors: Campins Lluis , Camps Marcella , Riera Ariadna , Pleguezuelos Eulogio , Yebenes Juan Carlos , Serra-Prat Mateu
Published: August 2016

Sarcopenia is a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and function. Reported prevalence of this geriatric syndrome, differs depending on the definition, the population and the method used to identify sarcopenia. The causes of sarcopenia are multifactorial, and can include genetic influence, immobility or disuse, endocrine factors, inflammation and nutritional deficiencies. These disorders involve an imbalance between anabolic and catabolic pathways that rules muscle mass. Many drugs taken regularly for common conditions may interact with some mechanisms that can alter the balance between protein synthesis and degradation. This may lead to a harmful or a beneficial effect on muscle mass and strength. Widely prescribed drugs could play an important role during the time of onset and development of sarcopenia. In this paper, we reviewed the current understanding of how can drugs contribute positively or negatively on sarcopenia and muscle wasting. We decided to focus this review on oral common drugs, which are usually prescribed in older adults, leaving aside other drugs as hormone therapy.
Predicting Lung Volume Reduction after Endobronchial Valve Therapy Is Maximized Using a Combination of Diagnostic Tools
Authors: Koster T. David , van Rikxoort Eva M. , Huebner Ralf-Harto , Doellinger Felix , Klooster Karin , Charbonnier Jean-Paul , Radhakrishnan Sri , Herth Felix J.F. , Slebos Dirk-Jan
Published: August 2016

Background: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis. Objectives: We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy. Methods: CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group. Results: A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%. Conclusion: Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy.
New Onset Hypertension Linked to Generic Cyclosporine Substitution in Post-Renal Transplant Patient
Authors: Al Dhaybi Omar , Bakris George
Published: August 2016

This is case report and review of the literature focused on generic substitutions of cyclosporine and its consequences. The pharmacokinetics and pharmacodynamics of the generic substitutions are clear different than the parent compound Sandimmune and can lead to different outcomes, as was the case in this report. A detailed accounting of the patients history led to the discovery of the problem and sorting back to a the branded drug supported the hypothesis.
Serum Endotoxin Activity Measured with Endotoxin Activity Assay Is Associated with Serum Interleukin-6 Levels in Patients on Chronic Hemodialysis
Authors: Bossola Maurizio , Di Stasio Enrico , Sanguinetti Maurizio , Posteraro Brunella , Antocicco Manuela , Pepe Gilda , Mello Enrica , Bugli Francesca , Vulpio Carlo
Published: August 2016

Background: This study aims to evaluate, in patients on chronic hemodialysis (PHD), the levels of endotoxin through a chemiluminescent bioassay based on the oxidative burst reaction of activated neutrophils to complement coated LPS-IgM immune complexes and define the variables possibly correlated. Methods: In 61 PHD, we measured serum endotoxin activity (EA) with the Endotoxin Activity Assay (EAA™) and we defined the possible association with demographic, clinical and laboratory variables. Results: Mean serum EA was 0.43 ± 0.26 UI. EA was low (<0.40) in 29 patients (47.5%), intermediate (0.40-0.60) in 14 (23%) and high (>0.60) in 18 (29.5%). A significant exponential relationship was detected between EA and serum interleukin-6 (IL-6) levels (r = 0.871). At the multiple regression analysis, intermediate-high EA was directly associated only with serum IL-6 levels. In a second model of multiple regression analysis without the variable serum IL-6 levels, intermediate-high EA was directly associated with constipation and serum troponin levels and inversely associated with serum albumin and the monthly number of sevelamer tablets. Conclusions: A high percentage of PHD has intermediate or high EA. Intermediate-high EA is significantly associated with serum IL-6 levels.
CD4 Decay Rate as an Indicator of the Time Interval between Initial Infection and First Diagnosis among Drug-Naïve Human Immunodeficiency Virus Seropositive Individuals in Lagos, Nigeria
Authors: Motayo Babatunde Olanrewaju , Aturaka Samson O. , Olusola Babatunde A. , Ogiogwa I. Joseph , Shidali Nataniel N. , Akingbade Olusola , Faneye Adedayo O.
Published: August 2016

Objective: The aim of this study was to determine the time interval between human immunodeficiency virus (HIV) infection and the first diagnosis among drug-naïve individuals in Badagry, Nigeria. Subjects and Methods: A sample of 213 subjects who tested HIV positive for the first time were enrolled in this study. The HIV diagnosis was performed using Startpak® and Determine® kits, and a CD4 count was carried out using a FACS Count® flow cytometer. The mean CD4 values were determined by gender and age groups. The time interval between initial HIV infection and first testing was calculated based on the average CD4 decay rate per calendar year, and data analysis was performed using SPSS software. Results: At diagnosis, the mean CD4 values showed that females recorded 270 cells/µl and males 244 cells/µl. By age range, individuals <25 years recorded 437 cells/µl, those between 25 and 40 years of age had 237 cells/µl, and those aged ≥41 years had 192 cells/µl. There was a significant difference between CD4 cell categorization and age range (p < 0.001). Subjects aged between 25 and 40 years recorded the highest distribution of all CD4 cell counts. The time interval between infection and testing for females was 8.1 years and for males 6.7 years. Within the age group <25 years the interval was 5.1 years, whilst it was 8.1 years for those aged ≥41 years. Conclusion: Most of the population presented for testing during the advanced stages of infection. We suggest an upscaling of HIV voluntary counseling and testing to encourage early detection and better treatment outcomes.
Lógicas das competências: Perspectivas para o Currículo em Ação
Authors: Medeiros Mário
Published: August 2016

(analítico): A polissemia do conceito de competência coloca dificuldades operacionais que podem se expressar em resultados opostos ao que se espera da organização do trabalho e de práticas pedagógicas orientadas por ele. Assumir um sentido mais preciso, mais circunscrito, mais nítido desse conceito só é possível se visualizarmos a lógica ou referencial teórico-metodológico em que ele se inscreve. Esse artigo é uma tentativa de contribuir para o aclaramento desses referenciais. Nele, utilizamo-nos da Hermenêutica de Suspeição e de Recuperação para identificar as Lógicas dentro das quais o conceito de competências induz a diferentes práticas. Identificadas as Lógicas Condutivista, Funcionalista, Cognitiva/Construtivista bem como as possibilidades e limites que elas apresentam, terminamos por propor a Lógica Sócio-Crítica Interacional que entendemos ser uma alternativa melhor sintonizada com propostas educativas mais democráticas.
Trayectorias, misiones e identidades de la Universidad latinoamericana
Authors: Marín-Gutiérrez María Piedad
Published: August 2016

(descriptivo): El presente artículo es fruto de la revisión y sistematización de la literatura como estado del arte, que intenta analizar el saber preexistente y lo acumulado en investigaciones con mayor relevancia y/o pertinencia sobre: ¿cuáles son las identidades de la universidad latinoamericana entre la razón, el mercado y el contexto? Busqué abordar las categorías identidad, misión, gestión, comunicación organizacional y publicitaria, que fueron la base para el rastreo bibliográfico que dio forma a una estructura categorial de análisis. El presente escrito evidencia la evolución y tránsito de la Universidad en Latinoamérica mostrando múltiples panoramas y realidades, en algunos casos contradictorios, pero que son propios de una universidad constituida por identidades plurales.
Habilidades sociales: Su importancia en mujeres con diagnóstico de Síndrome de Turner
Authors: Sartori María Soledad , Carolina López Marcela
Published: August 2016

(descriptivo): La Psicología Positiva postula la importancia de trabajar desde una mirada integradora de cada persona incluyendo sus fortalezas y debilidades. Esta mirada resulta importante al trabajar con poblaciones físicas, psicológicas y socialmente vulnerables. El Síndrome de Turner es un trastorno cromosómico determinado por la deleción del cromosoma X en el sexo femenino, siendo la talla y la disgenesia gonadal sus principales características físicas. Las mismas tienen un gran impacto en el desarrollo psicológico de esta población generando problemas en la capacidad de establecer relaciones sociales óptimas. El objetivo del presente trabajo es referenciar la importancia del desarrollo de habilidades sociales en el Síndrome de Turner, principalmente durante la niñez y la adolescencia, considerando que las mismas operan como un recurso salugénico para evitar trastornos mayores en la vida adulta.
Procesos de aprendizaje en niños de 6 a 10 años de edad con antecedente de nacimiento prematuro
Authors: Ríos-Flórez Jorge Alexander , Cardona-Agudelo Viviana
Published: August 2016

(analítico): En este estudio sobre los procesos de aprendizaje en niños y niñas prematuros, buscamos establecer las características del desempeño del niño o la niña pretérmino en las actividades base del aprendizaje, en comparación con un grupo de niños y niñas nacidos a término,entre 6 y 10 años de edad. Seleccionamos la muestra según un modelo no probabilístico y voluntario, con un total de 160 participantes, divididos en un grupo clínico de 80 niños y niñas prematuros y otro grupo de 80 niños y niñas nacidos a término. El enfoque empleado para esta investigación es de tipo cuantitativo y el diseño que utilizamos fue comparativo-correlacional, con la aplicación de subtest para evaluar procesos de escritura, lectura, cálculo y lenguaje, siendo la comprensión y la discriminación fonológica las principales dificultades para las personas prematuras, así como procesos de cálculo mental.
Análisis longitudinal del impacto de un programa de alfabetización temprana
Authors: Rosemberg Celia Renata , Stein Alejandra
Published: August 2016

(analítico): Se presenta un estudio longitudinal del desempeño de niños que participaron de un programa de promoción del desarrollo lingüístico en el jardín de infantes y en 1° grado del nivel primario. Un grupo de niños participantes (198) fue evaluado en vocabulario pasivo y productivo, escritura y lectura; su desempeño fue comparado con el de un grupo control (43).Se observó un mejor desempeño de los niños participantes, tanto en el jardín de infantes como en 1°grado. El análisis de regresión múltiple mostró que algunas de las habilidades evaluadas en el Nivel Inicial predicen el desempeño de los niños en 1° grado. Los resultados destacan la relevancia de una intervención planificada y sistemática en el Nivel Inicial con el fin de conseguir logros observables en el desempeño de los niños.