bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Medial Tibial Stress Syndrome according to the Fascial Distortion Model: A Prospective Case Control Study
Authors: Schulze Christoph , Finze Susanne , Bader Rainer , Lison Andreas
Published: October 2014

Medial tibial stress syndrome (MTSS) is a common problem among athletes and soldiers. There is no proven theory that could explain the pathophysiology of shin splints. The therapies described so far are time-consuming and involve a high risk of relapse. The method according to the fascial distortion model (FDM) addresses local changes in the area of the lower leg fascia. It is suited to reduce pain and functional impairments associated with this symptom complex by applying targeted manual techniques. 32 patients (male: 30; female: 2) participated in this study. Visual analogue scale (VAS) was used for the quantification of pain. Scores were also given to rate the maximum painless exercise tolerance of the patients. Subsequently treatment of the crural fascia was performed. Patients retested ability of running and jumping. Therapy was continued until full exercise tolerance or painlessness was reached. A significant reduction of the VAS pain score from 5.2 to 1.1 could be achieved(P<0.001). The impairment of exercise tolerance could be reduced from 7 to 2 points(P<0.001). The duration of treatment was 6.3 (SD: 4.3) days on average. The FDM therapy is a potential effective method for acute treatment of MTSS.
Classical Bianchi Type I Cosmology in K-Essence Theory
Authors: Socorro J. , Pimentel Luis O. , Espinoza-García Abraham
Published: October 2014

We use one of the simplest forms of the K-essence theory and we apply it to the classical anisotropic Bianchi type I cosmological model, with a barotropic perfect fluid (p=γρ) modeling the usual matter content and with cosmological constantΛ. Classical exact solutions for anyγ≠1andΛ=0are found in closed form, whereas solutions forΛ≠0are found for particular values in the barotropic parameter. We present the possible isotropization of the cosmological model Bianchi I using the ratio between the anisotropic parameters and the volume of the universe. We also include a qualitative analysis of the analog of the Friedmann equation.
Development and Validation of Protein Microarray Technology for Simultaneous Inflammatory Mediator Detection in Human Sera
Authors: Selvarajah Senthooran , Negm Ola H. , Hamed Mohamed R. , Tubby Carolyn , Todd Ian , Tighe Patrick J. , Harrison Tim , Fairclough Lucy C.
Published: October 2014

Biomarkers, including cytokines, can help in the diagnosis, prognosis, and prediction of treatment response across a wide range of disease settings. Consequently, the recent emergence of protein microarray technology, which is able to quantify a range of inflammatory mediators in a large number of samples simultaneously, has become highly desirable. However, the cost of commercial systems remains somewhat prohibitive. Here we show the development, validation, and implementation of an in-house microarray platform which enables the simultaneous quantitative analysis of multiple protein biomarkers. The accuracy and precision of the in-house microarray system were investigated according to the Food and Drug Administration (FDA) guidelines for pharmacokinetic assay validation. The assay fell within these limits for all but the very low-abundant cytokines, such as interleukin- (IL-) 10. Additionally, there were no significant differences between cytokine detection using our microarray system and the “gold standard” ELISA format. Crucially, future biomarker detection need not be limited to the 16 cytokines shown here but could be expanded as required. In conclusion, we detail a bespoke protein microarray system, utilizing well-validated ELISA reagents, that allows accurate, precise, and reproducible multiplexed biomarker quantification, comparable with commercial ELISA, and allowing customization beyond that of similar commercial microarrays.
Antimicrobial Photodynamic Therapy and Dental Plaque: A Systematic Review of the Literature
Authors: Santin G. C. , Oliveira D. S. B. , Galo R. , Borsatto M. C. , Corona S. A. M.
Published: October 2014

Background. The aim of this study was to perform a systematic review of the literature on the efficacy of antimicrobial photodynamic therapy (PDTa) on cariogenic dental biofilm.Types of Studies Reviewed. Studiesin vivo,in vitro, andin situwere included. Articles that did not address PDTa, those that did not involve cariogenic biofilm, those that used microorganisms in the plankton phase, and reviews were excluded. Data extraction and quality assessments were performed independently by two raters using a scale.Results. Two hundred forty articles were retrieved; only seventeen of them met the eligibility criteria and were analyzed in the present review. Considerable variability was found regarding the methodologies and application protocols for antimicrobial PDTa. Two articles reported unfavorable results.Practical Implications. The present systematic review does not allow drawing any concrete conclusions regarding the efficacy of antimicrobial PDTa, although this method seems to be a promising option.
Mapping Soil Surface Macropores Using Infrared Thermography: An Exploratory Laboratory Study
Authors: de Lima João L. M. P. , Abrantes João R. C. B. , Silva Valdemir P. , de Lima M. Isabel P. , Montenegro Abelardo A. A.
Published: October 2014

Macropores and water flow in soils and substrates are complex and are related to topics like preferential flow, nonequilibrium flow, and dual-continuum. Hence, the quantification of the number of macropores and the determination of their geometry are expected to provide a better understanding on the effects of pores on the soil’s physical and hydraulic properties. This exploratory study aimed at evaluating the potential of using infrared thermography for mapping macroporosity at the soil surface and estimating the number and size of such macropores. The presented technique was applied to a small scale study (laboratory soil flume).
Analytic and Approximate Solutions of the Space-Time Fractional Schrödinger Equations by Homotopy Perturbation Sumudu Transform Method
Authors: Hamed Sara H. M. , Yousif Eltayeb A. , Arbab Arbab I.
Published: October 2014

A combination of homotopy perturbation method and Sumudu transform is applied to find exact and approximate solution of space and time fractional nonlinear Schrödinger equation. The fractional derivatives are described in the Caputo sense. The solutions are given in the form of convergent series with easily computable components. The results show that the method is effective and convenient for solving nonlinear differential equations of fractional order.
Electrochemically Reduced Water Protects Neural Cells from Oxidative Damage
Authors: Kashiwagi Taichi , Yan Hanxu , Hamasaki Takeki , Kinjo Tomoya , Nakamichi Noboru , Teruya Kiichiro , Kabayama Shigeru , Shirahata Sanetaka
Published: October 2014

Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2(50–200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca2+influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW.
Comprasion of ICare Rebound Tonometer and Goldmann Applanation Tonometer in High Myopia
Authors: Cagatay Halil Huseyin , Ekinci Metin , Yazar Zeliha , Gokce Gokcen , Ceylan Erdinc
Published: October 2014

Purpose.To compare intraocular pressure (IOP) measurements with the Goldmann applanation tonometer (GAT) and the ICare rebound tonometer (RBT) in high myopic eyes.Patients and Methods. This randomized prospective study included 40 eyes of 40 patients with high myopia. All patients’ central corneal thickness (CCT), anterior chamber depth (ACD), axial length (AXL), keratometry, and refractive measurements were recorded and followed by IOP measurement with RBT and GAT.Results. The average CCT, AXL, and ACD were determined to be514.65±32 μm,27.65±2.22 mm, and3.25±0.51 mm, respectively. MeanKwas43.27±1.4 D and mean spherical equivalent was-11.31±4.30 D. The mean IOP values obtained by RBT and GAT were17.18±3.72 mmHg and16.48±3.19 mmHg, respectively. The deviations of RBT readings from corrected GAT values were highly correlated with CCT values (r=0.588,P=0.0001). The mean corrected GAT reading was17.49±3.01 mmHg. Linear regression analysis showed that a CCT change of 10 μm resulted in an RBT reading deviation of 0.57 mmHg. The Bland-Altman scatter-plot and McNemar test showed a clinically good level of agreement between the two tonometers.Conclusion. This study found a good agreement level between the two tonometers in high myopic patients and that RBT measurements are influenced by CCT variations.
Plasmonic and Thermooptical Properties of Spherical Metallic Nanoparticles for Their Thermoplasmonic and Photonic Applications
Authors: Pustovalov Victor K. , Astafyeva Liudmila G. , Fritzsche Wolfgang
Published: October 2014

Investigations and use of nanoparticles (NPs) as photothermal (PT) agents in laser and optical nanotechnology are fast growing areas of research and applications. The potential benefits of NPs applications include possibility for thermal imaging and treatment of materials containing of NPs, applications of NPs for light-to-thermal energy conversion, in catalysis, laser nanomedicine, and chemistry. Efficiency of applications of metallic NPs for laser and optical nanotechnology depends on plasmonic and thermophysical properties of NPs, characteristics of radiation, and surrounding medium. Here we present the results of comparative analysis of NP properties (plasmonic, thermooptical, and others) allowing selecting their parameters for thermoplasmonic and photonic applications. Plasmonic and thermooptical properties of several metallic (aurum, silver, platinum, cobalt, zinc, nickel, titanium, cuprum, aluminum, molybdenum, vanadium, and palladium) NPs are theoretically investigated and analysis of them is carried out. Investigation of the influence of NPs parameters (type of metal, radii, optical indexes, density, and heat capacity of NP material), characteristics of radiation (wavelength and pulse duration), and ambient parameters on plasmonic and thermophysical properties of NPs has been carried out. It was established that maximum value of thermooptical parameter (maximum NP temperature) can be achieved with the use of absorption efficiency factor of NP smaller than its maximum value.
Execution Behavior Modeling Methodology for Large Scale Surveillance System Design and Evaluation
Authors: Oh Jung-Min , Kim Kyung Hoon , Hong Sangjin , Moon Nammee
Published: October 2014

This paper presents a performance and evaluation environment for complex surveillance system design. The system consists of environment model, execution model, and application and evaluation model. The environment model interprets the script and creates objects in a surveillance environment so that various situations can be evaluated. The execution model modifies generated data with the perspective of each sensor and reflects algorithm execution behavior. The application model allows building large scale collaborative operations. The system behavior is parameterized for simple representations. The feasibility of the proposed method is illustrated through the case studies for improving the prototype surveillance system.
On Full-State Hybrid Projective Synchronization of General Discrete Chaotic Systems
Authors: Ouannas Adel
Published: October 2014

The problems of full-state hybrid projective synchronization (FSHPS) and inverse full-state hybrid projective synchronization (IFSHPS) for general discrete chaotic systems are investigated in 2D. Based on nonlinear control method and Lyapunov stability theory, new controllers are designed to study FSHPS and IFSHPS, respectively, for 2D arbitrary chaotic systems in discrete-time. Numerical example and simulations are used to validate the main results of this paper.
Clinic Type and Patient Characteristics Affecting Time to Resolution after an Abnormal Cancer-Screening Exam
Authors: Krok-Schoen Jessica L. , Kurta Michelle L. , Weier Rory C. , Young Greg S. , Carey Autumn B. , Tatum Cathy M. , Paskett Electra D.
Published: October 2014

Background: Research shows that multilevel factors influence healthcare delivery and patient outcomes. The study goal was to examine how clinic type [academic medical center (AMC) or federally qualified health center (FQHC)] and patient characteristics influence time to resolution (TTR) among individuals with an abnormal cancer-screening test enrolled in a patient navigation (PN) intervention.

Methods: Data were obtained from the Ohio Patient Navigation Research Project, a group-randomized trial of 862 patients from 18 clinics in Columbus, Ohio. TTR of patient after an abnormal breast, cervical, or colorectal screening test and the clinics' patient and provider characteristics were obtained. Descriptive statistics and Cox shared frailty proportional hazards regression models of TTR were used.

Results: The mean patient age was 44.8 years and 71% of patients were white. In models adjusted for study arm, FQHC patients had a 39% lower rate of resolution than AMC patients (P = 0.004). Patient factors of having a college education, private insurance, higher income, and being older were significantly associated with lower TTR. After adjustment for factors that substantially affected the effect of clinic type (patient insurance status, education level, and age), clinic type was not significantly associated with TTR.

Conclusions: These results suggest that TTR among individuals participating in PN programs are influenced by multiple socioeconomic patient-level factors rather than clinic type. Consequently, PN interventions should be tailored to address socioeconomic status factors that influence TTR.

Impact: These results provide clues regarding where to target PN interventions and the importance of recognizing predictors of TTR according to clinic type. Cancer Epidemiol Biomarkers Prev; 24(1); 162–8. ©2014 AACR.
Lung Cancer Detectability by Test, Histology, Stage, and Gender: Estimates from the NLST and the PLCO Trials
Authors: ten Haaf Kevin , van Rosmalen Joost , de Koning Harry J.
Published: October 2014

Background: Implementing optimal lung cancer screening programs requires knowledge of the natural history and detectability of lung cancer. This information can be derived from the results of clinical trials with the aid of microsimulation models.

Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) program and individual-level data from the National Lung Screening Trial (NLST) and the Prostate, Lung, Colon, and Ovarian Cancer Screening trial (PLCO) were used to investigate the sensitivity (by histology and stage) of CT and chest radiography (CXR) and the mean preclinical sojourn time (MPST) of lung cancer (by gender, histology, and stage). The MISCAN-Lung model was used to reproduce the lung cancer incidence by method of detection (clinically or screen-detected), gender, histology, and stage in both trials and SEER, by calibrating CT and CXR sensitivity and natural history parameters.

Results: CT sensitivity ranges from 8.83% to 99.35% and CXR sensitivity from 2.51% to 97.31%, depending on histology and stage. CT sensitivity for stage IA is more than 3-fold higher compared with CXR, for all histologies. The total MPST estimates for lung cancer progressing through preclinical stages IA to IV range from 3.09 to 5.32 years for men and 3.35 to 6.01 years for women. The largest difference in total MPST between genders was estimated for adenocarcinoma.

Conclusions: We estimate longer MPSTs for lung cancer compared with previous research, suggesting a greater window of opportunity for lung cancer screening.

Impact: This study provides detailed insights into the natural history of lung cancer and CT screening effectiveness. Cancer Epidemiol Biomarkers Prev; 24(1); 154–61. ©2014 AACR.
RRAD Promotes EGFR-Mediated STAT3 Activation and Induces Temozolomide Resistance of Malignant Glioblastoma
Authors: Yeom Seon-Yong , Nam Do-Hyun , Park Chaehwa
Published: October 2014

Glioblastoma multiforme (GBM) is an extremely aggressive brain cancer with a median survival of less than 2 years. GBM is characterized by abnormal activation of receptor tyrosine kinase and constitutively activated STAT3. Although EGFR phosphorylation and STAT3 activation are essential for the maintenance of GBM cancer stem cells, the molecular mechanism underlying endosome-mediated STAT3 activation is not fully understood. In the current study, we showed that GTP-binding protein RRAD (RAS associated with diabetes, RAD) physically associates with EGFR, and EEA1, enhancing the stability and endosome-associated nuclear translocation of EGFR. Functionally, RRAD contributes to the activation of STAT3 and expression of the stem cell factors OCT4, NANOG, and SOX2, thereby enhancing self-renewing ability, tumor sphere formation, EMT, and in vivo tumorigenesis. Most importantly, RRAD contributes to poor survival in patients with GBM. RRAD expression is correlated with temozolomide resistance, and, conversely, depletion of RRAD leads to sensitization of highly temozolomide-resistant GBM cells. Our data collectively support a novel function of RRAD in STAT3 activation and provide evidence that RRAD acts as a positive regulator in the EGFR signaling pathway. These results demonstrate a critical role for RRAD in GBM tumorigenesis and provide a rationale for the development of pharmacologic inhibitors of RRAD in GBM. Mol Cancer Ther; 13(12); 3049–61. ©2014 AACR.
The Chemokine (CCL2–CCR2) Signaling Axis Mediates Perineural Invasion
Authors: He Shizhi , He Shuangba , Chen Chun-Hao , Deborde Sylvie , Bakst Richard L. , Chernichenko Natalya , McNamara William F. , Lee Sei Young , Barajas Fernando , Yu Zhenkun , Al-Ahmadie Hikmat A. , Wong Richard J.
Published: October 2014

Perineural invasion is a form of cancer progression where cancer cells invade along nerves. This behavior is associated with poor clinical outcomes; therefore, it is critical to identify novel ligand–receptor interactions between nerves and cancer cells that support the process of perineural invasion. A proteomic profiler chemokine array was used to screen for nerve-derived factors secreted from tissue explants of dorsal root ganglion (DRG), and CCL2 was identified as a lead candidate. Prostate cancer cell line expression of CCR2, the receptor to CCL2, correlated closely with MAPK and Akt pathway activity and cell migration towards CCL2 and DRG. In vitro nerve and cancer coculture invasion assays of perineural invasion demonstrated that cancer cell CCR2 expression facilitates perineural invasion. Perineural invasion is significantly diminished in coculture assays when using DRG harvested from CCL2−/− knockout mice as compared with control CCL2+/+ mice, indicating that CCR2 is required for perineural invasion in this murine model of perineural invasion. Furthermore, 20 of 21 (95%) patient specimens of prostate adenocarcinoma with perineural invasion exhibited CCR2 expression by immunohistochemistry, while just 3 of 13 (23%) lacking perineural invasion expressed CCR2. In summary, nerve-released CCL2 supports prostate cancer migration and perineural invasion though CCR2-mediated signaling.

Implications: These results reveal CCL2–CCR2 signaling as a key ligand–receptor mechanism that mediates cancer cell communication with nerves during perineural invasion and highlight a potential future therapeutic target. Mol Cancer Res; 13(2); 380–90. ©2014 AACR.
SPAK and OSR1 Dependent Down-Regulation of Murine Renal Outer Medullary K+ Channel ROMK1
Authors: Elvira Bernat , Munoz Carlos , Borras Jose , Chen Hong , Warsi Jamshed , Ajay Sumant Singh , Shumilina Ekaterina , Lang Florian
Published: October 2014

Background/Aims: The kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) participate in the regulation of the NaCl cotransporter NCC and the Na+,K+,2Cl- cotransporter NKCC2. The kinases are regulated by WNK (with-no-K[Lys]) kinases. Mutations of genes encoding WNK kinases underly Gordon's syndrome, a monogenic disease leading to hypertension and hyperkalemia. WNK kinases further regulate the renal outer medullary K+ channel ROMK1. The present study explored, whether SPAK and/or OSR1 have similarly the potential to modify the activity of ROMK1. Methods: ROMK1 was expressed in Xenopus oocytes with or without additional expression of wild-type SPAK, constitutively active T233ESPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1 and catalytically inactive D164AOSR1. Channel activity was determined utilizing dual electrode voltage clamp and ROMK1 protein abundance in the cell membrane utilizing chemiluminescence of ROMK1 containing an extracellular hemagglutinin epitope (ROMK1-HA). Results: ROMK1 activity and ROMK1-HA protein abundance were significantly down-regulated by wild-type SPAK and T233ESPAK, but not by D212ASPAK. Similarly, ROMK1 activity and ROMK1-HA protein abundance were significantly down-regulated by wild-type OSR1 and T185EOSR1, but not by D164AOSR1. Conclusion: ROMK1 protein abundance and activity are down-regulated by SPAK and OSR1.
Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy
Authors: Wang Jinling , Cao Juan
Published: October 2014

Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs) between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus) database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO) enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap) database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.
Marital Status and Cognitive Impairment among Community-Dwelling Chinese Older Adults: The Role of Gender and Social Engagement
Authors: Feng Lei , Ng Xue-Ting , Yap Philip , Li Jialiang , Lee Tih-Shih , Håkansson Krister , Kua Ee-Heok , Ng Tze-Pin
Published: October 2014

Aims: To examine the association between marital status and cognitive impairment among community-dwelling Chinese older adults. Methods: We analyzed data from 2,498 Chinese aged 55 and older from the Singapore Longitudinal Aging Study cohort. Cognitive impairment was defined as a Mini-Mental State Examination total score of 23 or below. Odds ratios of associations were reported and adjusted for potential confounders in logistic regression models. Results: The prevalence of cognitive impairment was 12.2% (n = 306). Being single was associated with about 2.5 times increased odds of cognitive impairment compared to being married (adjusted OR = 2.53, 95% CI: 1.41-4.55). The association between marital status and cognitive impairment was much stronger in men compared to that in women, and was indeed statistically significant only for men. Among the single and widowed persons social engagement was associated with a lower risk of cognitive impairment. Compared with subjects in the lowest tertile of social engagement scores, the odds of having cognitive impairment was lowered by 50% for subjects in the second and the third tertile. Conclusion: Being single or widowed was associated with higher odds of cognitive impairment compared to being married in a cohort of older Chinese men but not women.
Frontomaxillary Facial Angle Measurement in Trisomy 21 and Euploid Fetuses: Two- and Three-Dimensional Assessment during Routine First Trimester Screening
Authors: Alphonse Jennifer , Cox Jenny , Clarke Jillian L. , Schluter Philip J. , McLennan Andrew
Published: October 2014

Objective: To assess 2D and 3D frontomaxillary facial angle (FMFA) measurements in euploid and trisomy 21 fetuses. Materials and Methods: Over a 2-year period, women with singleton pregnancies attending a private prenatal screening and diagnosis practice in Sydney, Australia, were invited to participate in this study where 2D images and 3D volumes of the fetal face were collected during routine first trimester screening. In pregnancies where trisomy 21 was confirmed, FMFA measurements were performed in 2D and 3D and compared with those from a euploid cohort. Results: Overall, 250 women carrying euploid and 22 women carrying trisomy 21 fetuses participated. Trisomy 21 fetuses had significantly larger FMFA measurements than euploid fetuses in both 2D and 3D assessments. 95% of 3D and 100% of 2D FMFA measurements for the trisomy 21 fetuses were above the mean FMFA measurement of the euploid fetuses. There was no relationship between increasing crown-rump length and FMFA measurement. Conclusion: 2D and 3D FMFA measurements in trisomy 21 fetuses are statistically greater (p < 0.001) than those in euploid fetuses. This supports FMFA as a possible additional marker for trisomy 21 for first trimester screening.
Plaque pH in Caries-Free and Caries-Active Young Individuals before and after Frequent Rinses with Sucrose and Urea Solution
Authors: Hassan Haidar , Lingström Peter , Carlén Anette
Published: October 2014

Objective: To examine pH in the approximal dental biofilm after acid and alkali formation from sucrose and urea, after an adaptation period to these substances, in caries-free (CF) and caries-active (CA) individuals. Saliva flow and buffer capacity, and aciduric bacteria in saliva and plaque were also examined. Material and Methods: Twenty adolescents and young adults (15-21 years) with no caries (n = 10, Dm + iMFS = 0) or ≥1 new manifest lesions/year (n = 10, DmMFS = 3.4 ± 1.8) participated. After plaque sampling, interproximal plaque pH was measured using the strip method before (baseline) and up to 30 min (final pH) after random distribution of a 1-min rinse with 10 ml of 10% sucrose or 0.25% urea. This procedure was repeated after a 1-week adaptation period of rinsing 5 times/day with 10 ml of the selected solution. After a 2-week washout period the second solution was similarly tested. Mutans streptococci, lactobacilli and pH 5.2-tolerant bacteria were analyzed by culturing. Results: In the CF group, acid adaptation resulted in lowering of baseline and final plaque pH values after a sugar challenge, and in increased numbers of bacteria growing at pH 5.2, which was increased also after alkali adaptation. In the CA group, the final pH was decreased after acid adaptation. No clear effects of alkali adaptation were seen in this group. Conclusion: One-week daily rinses with sucrose and urea had the most pronounced effect on the CF group, resulting in increased plaque acidogenicity from the sugar rinses and increased number of acid-tolerant plaque bacteria from both rinses.
Sphingoid Bases Inhibit Acid-Induced Demineralization of Hydroxyapatite
Authors: Valentijn-Benz Marianne , van ''t Hof Wim , Bikker Floris J. , Nazmi Kamran , Brand Henk S. , Sotres Javier , Lindh Liselott , Arnebrant Thomas , Veerman Enno C.I.
Published: October 2014

Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p < 0.001). On the other hand, sphingomyelin, acetyl PHS, octanoyl PHS and stearoyl PHS had no anti-erosive effects. Atomic force measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H+ ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products. © 2014 S. Karger AG, Basel
Pilot Trial of Systemic Methotrexate plus R-CHOP Regimen with Intrathecal Methotrexate for Simultaneous Central Nervous System and Systemic Diffuse Large B Cell Lymphoma
Authors: Yoo Kwai Han , Lee Ji Yun , Lim Sung Hee , Ko Young Hyeh , Kim Seok Jin , Kim Won Seog
Published: October 2014

Background: The simultaneous presentation of systemic diffuse large B cell lymphoma (DLBCL) with central nervous system (CNS) disease is not well controlled by either R-CHOP or systemic methotrexate (MTX) alone. Methods: We conducted a pilot trial with 6 patients who were initially diagnosed with systemic DLBCL with CNS involvement. Patients were treated with a systemic MTX plus R-CHOP regimen. Results: The overall response rate was 4/6 (66.7%). The CNS response rate and systemic response rate were 4/6 (66.7%) and 5/6 (83.3%), respectively. The median response duration of the 4 patients with complete remission at completion was 25.5 months, and the median survival of all patients was 25.1 months. CNS lesions progressed in all relapsed and refractory patients, while systemic disease progression was observed in 1 patient. No fatal hematologic adverse effects, hepatotoxicity or nephrotoxicity were observed. Conclusions: The dose of systemic MTX (1∼1.5 g/m2) or dose intensity (4-week interval in 4 patients) used in this trial was considered insufficient. Therefore, the dose of MTX or interval of each chemotherapy cycle should be modified in future trials to control CNS disease involved with DLBCL. © 2014 S. Karger AG, Basel
Pancreaticoduodenectomy with Harmonic Focust Curved Shears for Cancer
Authors: Salvia Roberto , Malleo Giuseppe , Marchegiani Giovanni , Butturini Giovanni , Esposito Alessandro , Bassi Claudio
Published: October 2014

Ultrasonically activated shears enable the effective cutting and hemostasis of tissue, and have been shown to offer significant benefits in surgical procedures requiring fine dissection. Harmonic Focust, one of the latest ultrasonic devices, is a clip-like, light-weight, hand-held instrument with curved thin shears. Experience with Harmonic Focus in pancreatic surgery is limited. We have performed more than 1,000 pancreatic resections with this device. It may well represent a valuable tool for the extensive tissue and vascular dissection that is required in pancreaticoduodenectomy. In particular, Harmonic Focus performs very well in lymph node dissection, which is central in cancer surgery. In this report, we describe pancreaticoduodenectomy for pancreatic-head and periampullary cancer with the Harmonic Focus device. i 2014 S. Karger AG, Basel
Ischemic Preconditioning Inhibits Mitochondrial Permeability Transition Pore Opening through the PTEN/PDE4 Signaling Pathway
Authors: Zheng Xiaoxu , Zu Lingyun , Becker Lewis , Cai Zheqing P.
Published: October 2014

Objectives: Ischemic preconditioning (IPC) induces cardioprotection against ischemia-reperfusion (IR) injury by inhibiting the mitochondrial permeability transition pore (mPTP). Here, we tested the hypothesis that IPC-induced cardioprotection is mediated by the phosphatase PTEN and PDE4 (phosphodiesterase 4). Methods: Isolated hearts from wild-type mice (WT, n = 110) and myocyte-specific PTEN-knockout mice (PKO, n = 94) were exposed to IPC or control conditions followed by IR. Subcellular fractionation was performed by sucrose gradient ultracentrifugation. Results: IPC limited myocardial infarct size (IS) in WT mice. The PDE4 inhibitor rolipram abolished the protective effect of IPC. However, small IS was found in PKO hearts after IR, and IPC did not decrease IS but enlarged it in PKO hearts. IPC promoted PDE4D localization to caveolin-3-enriched fractions in WT mice by increasing Akt levels at the caveolae. In PKO hearts, basal PDE4D levels were elevated at the caveolae, and IPC decreased PDE4D levels. Consistent with the subcellular PDE4D protein levels and its activity, elevation in intracellular Ca2+ levels in the ischemic heart and opening of mPTP after IR were inhibited by IPC in WT mice, but not by IPC in PKO mice. Conclusions: IPC inhibits mPTP opening by regulating the PTEN/PDE4 signaling pathway.
Insulin-Like Growth Factor-1 and Anti-Vascular Endothelial Growth Factor in Retinopathy of Prematurity: Has the Time Come
Authors: Stahl Andreas , Hellstrom Ann , Smith Lois E.H.
Published: October 2014

Treatment of retinopathy of prematurity (ROP) is currently evolving. Novel therapeutic options are emerging that have the potential to complement existing therapies and improve treatment outcomes. However, any new therapeutic option must be thoroughly evaluated before existing (and successful) treatment paradigms can be amended. This is particularly so when switching from locally effective therapies like photoablative laser therapy to systemic pharmacological treatments, which may have hitherto unknown widespread side effects. This review compiles the current knowledge of where and when the two most advanced pharmacological treatment options for ROP, insulin-like growth factor-1 supplementation and anti-vascular endothelial growth factor treatment, may have their place in future therapy regimens for ROP. The requirement for clinical studies is emphasized: these are needed to address safety considerations before any of these interventions can achieve the status of standard clinical care in the very vulnerable population of ROP infants.
Neovascularization Precedes Occlusion in Moyamoya Disease: Angiographic Findings in 172 Pediatric Patients
Authors: Kim Suk Jae , Son Tae Ok , Kim Keon Ha , Jeon Pyoung , Hyun Seung Hyup , Lee Kyung-Han , Yeon Je Young , Kim Jong-Soo , Hong Seung-Chyul , Shin Hyung Jin , Bang Oh Young
Published: October 2014

Background: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. Methods: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. Results: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. Conclusion: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.
Effect of Physical Exercise on Cognitive Performance in Older Adults with Mild Cognitive Impairment or Dementia: A Systematic Review
Authors: Öhman Hanna , Savikko Niina , Strandberg Timo E. , Pitkälä Kaisu H.
Published: October 2014

Numerous studies have shown that physical exercise has positive effects on cognition in healthy adults. Less is known about the effectiveness of exercise interventions in older individuals already suffering from mild cognitive impairment (MCI) or dementia. The aim of this study was to systematically review the evidence from randomized controlled trials (RCTs) of the effects of physical exercise on cognition in older subjects with MCI or dementia. PubMed, Cochrane and DARE databases were systematically searched for RCTs using terms related to cognition and physical exercise. Altogether, 22 trials were found. The studies on older subjects with MCI reported some positive effects of physical exercise on cognition, mainly on global cognition, executive function, attention and delayed recall. However, most studies performed on older subjects with dementia showed no effect of exercise on cognition. The studies had methodological problems in defining dementia/MCI diagnosis, blinding, inadequate sample sizes and not reporting dropouts, compliance or complications. More studies of good quality on older adults with dementia are needed.
β Integrins Mediate FAK Y397 Autophosphorylation of Resistance Arteries during Eutrophic Inward Remodeling in Hypertension
Authors: Heerkens Egidius H.J. , Quinn Lisa , Withers Sarah B. , Heagerty Anthony M.
Published: October 2014

Human essential hypertension is characterized by eutrophic inward remodeling of the resistance arteries with little evidence of hypertrophy. Upregulation of αVβ3 integrin is crucial during this process. In order to investigate the role of focal adhesion kinase (FAK) activation in this process, the level of FAK Y397 autophosphorylation was studied in small blood vessels from young TGR(mRen2)27 animals as blood pressure rose and eutrophic inward remodeling took place. Between weeks 4 and 5, this process was completed and accompanied by a significant increase in FAK phosphorylation compared with normotensive control animals. Phosphorylated (p)FAK Y397 was coimmunoprecipitated with both β1- and β3-integrin-specific antibodies. In contrast, only a fraction (<10-fold) was coprecipitated with the β3 integrin subunit in control vessels. Inhibition of eutrophic remodeling by cRGDfV treatment of TGR(mRen2)27 rats resulted in the development of smooth-muscle-cell hypertrophy and a significant further enhancement of FAK Y397 phosphorylation, but this time with exclusive coassociation of pFAK Y397 with integrin β1. We established that phosphorylation of FAK Y397 with association with β1 and β3 integrins occurs with pressure-induced eutrophic remodeling. Inhibiting this process leads to an adaptive hypertrophic vascular response induced by a distinct β1-mediated FAK phosphorylation pattern.
Recurrent Stroke in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial
Authors: Pullicino Patrick M. , Qian Min , Sacco Ralph L. , Freudenberger Ron , Graham Susan , Teerlink John R. , Mann Douglas , Di Tullio Marco R. , Ponikowski Piotr , Lok Dirk J. , Anker Stefan D. , Lip Gregory Y.H. , Estol Conrado J. , Levin Bruce , Mohr Jay P. , Thompson John L.P. , Homma Shunichi ,   for the WARCEF Investigators
Published: October 2014

Background and Purpose: WARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods: We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results: Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) <15% and 70 of 2,079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p < 0.001) and EF <15% vs. ≥15% (p = 0.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF <15% and 0.95/100PY in patients with EF ≥15% (p = 0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF <15% decreasing to 2.62/100PY with EF <30%. Conclusions: In a WARCEF exploratory analysis, prior stroke and EF <15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF.
PTEN Deficiency as a Predictive Biomarker of Resistance to HER2-Targeted Therapy in Advanced Gastric Cancer
Authors: Zhang Xianglan , Park Ji Soo , Park Kyu Hyun , Kim Ki Hyang , Jung Minkyu , Chung Hyun Cheol , Rha Sun Young , Kim Hyo Song
Published: October 2014

Background: To investigate the role of the phosphoinositide 3-kinase (PI3K) pathway activation in human epidermal growth factor receptor 2 (HER2)-targeted therapy. Methods: We evaluated the predictive roles of PI3K, catalytic alpha (PIK3CA), and phosphatase and tensin homolog (PTEN) in HER2-based therapy (either trastuzumab or lapatinib). PTEN expression and PIK3CA mutation were analyzed using immunohistochemistry and pyrosequencing. Results: Forty-eight patients received trastuzumab (n = 39) or lapatinib (n = 9) combination chemotherapy. PTEN loss was found in 47.9% (n = 23), but no PIK3CA mutations were identified. Twenty-six (54.1%) patients responded to HER2-based therapy, without a significant difference between patients with PTEN loss and those without (52.2 vs. 56.0%). Among the patients with responsive disease, time to best response did not differ by PTEN status, but the duration of response was significantly shorter for patients with PTEN loss (median 4.2 vs. 6.1 months, p = 0.04). In addition, patients with PTEN loss had a significantly shorter progression-free survival time (median 4.9 vs. 7.3 months, p = 0.047). Conclusions: PTEN deficiency is an important predictive marker for early resistance to HER2 inhibitor treatment in gastric cancer patients. This finding may be useful for the development of drug combinations and identification of patients who need a modified treatment strategy. © 2014 S. Karger AG, Basel
Collapsing Focal Segmental Glomerulosclerosis Resulting from a Single Dose of Zoledronate
Authors: Neyra Javier A. , Vaidya Omkar U. , Hendricks Allen , Sambandam Kamalanathan K.
Published: October 2014

Bisphosphonates are commonly used for the treatment of osteoporosis, Paget's disease, multiple myeloma and hypercalcemia. Collapsing focal segmental glomerulosclerosis (FSGS) is known to occur uncommonly with exposure to bisphosphonates, specifically pamidronate and alendronate; it has rarely and equivocally been reported with zoledronate therapy. We describe the case of a 36-year-old African American female with metastatic breast cancer who presented with nephrotic-range proteinuria and acute kidney injury within 2 weeks of exposure to a single dose of zoledronate. The patient had a partial recovery of her renal function and showed improved proteinuria to a subnephrotic level after discontinuing zoledronate. In contrast to 2 prior reports of zoledronate-induced collapsing FSGS, the causative role of the exposure described here is certain. Our case necessitates the addition of zoledronate to the list of known causes of collapsing FSGS. Furthermore, it highlights the importance of periodically monitoring renal function and urine protein excretion with the use of zoledronate, which allows prompt diagnosis and withdrawal of the drug to increase the probability of renal recovery.
Preeclampsia and Maternal Cardiovascular Disease: Consequence or Predisposition?
Authors: Osol George , Bernstein Ira
Published: October 2014

Formerly preeclamptic women stand a higher chance of developing cardiovascular disease (CVD) later in life and may experience a shortened life span. This review updates the pathophysiology and definition of this complex disease and highlights the protective role of pregnancy by considering the relationship between pregnancy interval and likelihood of disease recurrence. The evidence for persistent maternal cardiovascular impairment following preeclampsia (PE) is considered, e.g. postpartum changes in CVD occurrence, blood pressure elevation and changes in the renin-angiotensin-aldosterone system). Since maternal endothelial dysfunction is a hallmark of PE, we summarize the evidence for reduced flow-mediated dilation in women with previous PE, and consider the utility and shortcomings of this clinical measure. In addition to viewing postpartum changes as a consequence of this disease, we consider the alternative view that PE might be the manifestation of a maternal phenotype that already has some predisposition to or is in the earlier stages of CVD; in this case, some of the postpartum residual deficits (or their antecedents) may have already been present prior to pregnancy. Finally, we consider the use of novel biomarkers for predicting or detecting PE prior to the appearance of clinical symptoms.