bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlling Queue Delay
Authors: Nichols Kathleen , Jacobson Van
Published: May 2012

Nearly three decades after it was first diagnosed, the "persistently full buffer problem" recently exposed as part of "bufferbloat", is still with us and made increasingly critical by two trends. First, cheap memory and a "more is better" mentality have led to the inflation and proliferation of buffers. Second, dynamically varying path characteristics are much more common today and are the norm at the consumer Internet edge. Reasonably sized buffers become extremely oversized when link rates and path delays fall below nominal values.
Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media
Authors: Jung Sunghoon , Panchalingam Krishna M. , Rosenberg Lawrence , Behie Leo A.
Published: May 2012

Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.
TRIM22: A Diverse and Dynamic Antiviral Protein
Authors: Hattlmann Clayton J. , Kelly Jenna N. , Barr Stephen D.
Published: May 2012

The tripartite motif (TRIM) family of proteins is an evolutionarily ancient group of proteins with homologues identified in both invertebrate and vertebrate species. Human TRIM22 is one such protein that has a dynamic evolutionary history that includes gene expansion, gene loss, and strong signatures of positive selection. To date, TRIM22 has been shown to restrict the replication of a number of viruses, including encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), and human immunodeficiency virus type 1 (HIV-1). In addition, TRIM22 has also been implicated in cellular differentiation and proliferation and may play a role in certain cancers and autoimmune diseases. This comprehensive paper summarizes our current understanding of TRIM22 structure and function.
Peristaltic Transport of a Jeffrey Fluid with Variable Viscosity through a Porous Medium in an Asymmetric Channel
Authors: Afsar Khan A. , Ellahi R. , Vafai K.
Published: May 2012

The peristaltic flow of a Jeffrey fluid with variable viscosity through a porous medium in an asymmetric channel is investigated. The channel asymmetric is produced by choosing the peristaltic wave train on the wall of different amplitude and phase. The governing nonlinear partial differential equations for the Jeffrey fluid model are derived in Cartesian coordinates system. Analytic solutions for stream function, velocity, pressure gradient, and pressure rise are first developed by regular perturbation method, and then the role of pertinent parameters is illustrated graphically.
Methylation-Mediated Molecular Dysregulation in Clinical Oral Malignancy
Authors: Towle Rebecca , Garnis Cathie
Published: May 2012

Herein we provide a concise review of the state of methylation research as it pertains to clinical oral cancerous and precancerous tissues. We provide context for ongoing research efforts in this field and describe technologies that are presently being applied to analyze clinical specimens. We also discuss the various recurrent methylation changes that have been reported for oral malignancy (including those genes frequently silenced by promoter methylation and the small RNAs with activity modulated by methylation changes) and describe surrogate disease markers identified via epigenetic analysis of saliva and blood specimens from patients with oral cancer.
Single-Port Laparascopic Cholecystectomy: Scarless Cholecystectomy
Authors: Zubaidi Ahmad Mohmmad
Published: May 2012

Objective. Single-incision laparoscopic surgery is a new advanced technology to further minimize the invasiveness of laparoscopy through a single small incision hidden in the umbilicus. The objective is to describe short and long-term outcomes of SILS cholecystectomy.Methodology. Patients with gallbladder pathologies were unselectively enrolled and were prospectively studied between April 2009 and April 2010 and completed a post-operative follow-up for 12 months.Results. There were 22 women and 8 men. Mean age was 46 years. Twenty-one patients had biliary colic, seven had acute cholecystitis, one had gallbladder polyp, and another had resolving acute pancreatitis. Mean operative time was104.3±44minutes. Mean BMI was 30.42 and the average pain score was3.2±1.1. One more port was inserted to help in finishing the procedure in one patient. There was no conversion to a standard laparoscopic or open technique. There was one post-operative bile collection from a missed cyctic duct of Luschka. Mean hospital stay was 1.2 days.Conclusion. Single-port laparoscopic cholecystectomy is feasible. Early conversion to a standard laparoscopic technique is advised to avoid serious complications. The procedure has an obvious cosmetic benefit. Additional prospective trials are necessary to define the benefits of single-port laparoscopic cholecystectomy.
Event-Based Stabilization over Networks with Transmission Delays
Authors: Meng Xiangyu , Chen Tongwen
Published: May 2012

This paper investigates asymptotic stabilization for linear systems over networks based on event-driven communication. A new communication logic is proposed to reduce the feedback effort, which has some advantages over traditional ones with continuous feedback. Considering the effect of time-varying transmission delays, the criteria for the design of both the feedback gain and the event-triggering mechanism are derived to guarantee the stability and performance requirements. Finally, the proposed techniques are illustrated by an inverted pendulum system and a numerical example.
Male Stress Urinary Incontinence: A Review of Surgical Treatment Options and Outcomes
Authors: Trost Landon , Elliott Daniel S.
Published: May 2012

Introduction and Objective. Iatrogenic male stress urinary incontinence (SUI) affects a percentage of men undergoing urologic procedures with a significant impact on quality of life. The treatment of male SUI has evolved significantly with multiple current options for treatment available. The current paper discusses preoperative evaluation of male SUI, available surgical options with reported outcomes, and postoperative complication management.Methods. A pubMed review of available literature was performed and summarized on articles reporting outcomes of placement of the artificial urinary sphincter (AUS) or male slings including the bone anchored sling (BAS), retrourethral transobturator sling (RTS), adjustable retropubic sling (ARS), and quadratic sling.Results. Reported rates of success (variably defined) for BAS, RTS, ARS, and AUS are 36–67%, 9–79%, 13–100%, and 59–91% respectively. Complications reported include infection, erosion, retention, explantation, and transient pain. Male slings are more commonly performed in cases of low-to-moderate SUI with decreasing success with higher degrees of preoperative incontinence.Conclusions. An increasing number of options continue to be developed for the management of male SUI. While the AUS remains the gold-standard therapy for SUI, male sling placement is a proven viable alternative therapy for low-to-moderate SUI.
Diverse Spectrum of Presentation of Coronary Slow Flow Phenomenon: A Concise Review of the Literature
Authors: Chaudhry Muhammad A. , Smith Marcus , Hanna Elias B. , Lazzara Ralph
Published: May 2012

The coronary slow flow phenomenon (CSFP) is a disease entity characterized by slow progression of angiographic contrast in the coronary arteries in the absence of stenosis in the epicardial vessels. CSFP has a diverse presentation from mild chest discomfort to ST-segment elevation myocardial infarction. It can also have severe morbidity and mortality implications and can significantly hamper the quality of life of those affected. In this paper we present two patients with CSFP highlighting the diverse spectrum of presentation. A concise review of the literature is also provided emphasizing the epidemiology, pathogenesis, diagnostic parameters, treatment modalities, and clinical significance of this phenomenon.
Changes in Cardiac Autonomic Regulation after Acute Lung Exposure to Carbon Nanotubes: Implications for Occupational Exposure
Authors: Legramante Jacopo M. , Sacco Sergio , Crobeddu Patrizio , Magrini Andrea , Valentini Federica , Palleschi Giuseppe , Pallante Marco , Balocchi Rita , Iavicoli Ivo , Bergamaschi Antonio , Galante Alberto , Campagnolo Luisa , Pietroiusti Antonio
Published: May 2012

Carbon nanotubes (CNTs) are among the most relevant engineered nanomaterials (ENMs). Given the expected rise of exposure to ENMs, there is concern that they may adversely affect health of exposed people. Aim of the study was to test the hypothesis that single wall carbon nanotubes (SWCNTs) pulmonary exposure acutely affect the autonomic cardiovascular regulation in conscious rats. We studied Wistar‐Kyoto rats in which a telemetry transmitter for continuous arterial pressure (AP) and heart rate (HR) recordings was surgically implanted. SWCNTs dispersed in phosphate buffer saline (PBS) or PBS alone were randomly administered intratracheally. Immediately before, and 24 hours after each instillation a 30 min AP recording was performed. The sequence analysis was performed to evaluate the baroreflex function. In the control group, PBS instillation did not induce any significant changes. At variance the SWCNT exposure induced a significant reduction of baroreflex system (BRS) (3.5 ± 0.6 versus 2.6 ± 0.40 msec/mmHg) without significant changes in the occurrence of baroreflex sequences (7.5 ± 0.47% versus 7.4 ± 0.38%). Our results show that SWCNT pulmonary exposure might affect the cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events.
Pseudogenes
Authors: Tutar Yusuf
Published: May 2012

Pseudogenes are ubiquitous and abundant in genomes. Pseudogenes were once called “genomic fossils” and treated as “junk DNA” several years. Nevertheless, it has been recognized that some pseudogenes play essential roles in gene regulation of their parent genes, and many pseudogenes are transcribed into RNA. Pseudogene transcripts may also form small interfering RNA or decrease cellular miRNA concentration. Thus, pseudogenes regulate tumor suppressors and oncogenes. Their essential functions draw the attention of our research group in my current work on heat shock protein 90: a chaperone of oncogenes. The paper reviews our current knowledge on pseudogenes and evaluates preliminary results of the chaperone data. Current efforts to understand pseudogenes interactions help to understand the functions of a genome.
Ecklonia cavaInhibits Glucose Absorption and Stimulates Insulin Secretion in Streptozotocin-Induced Diabetic Mice
Authors: Kim Hye Kyung
Published: May 2012

Aims of study. Present study investigated the effect ofEcklonia cava(EC) on intestinal glucose uptake and insulin secretion.Materials and methods. Intestinal Na+-dependent glucose uptake (SGU) and Na+-dependent glucose transporter 1 (SGLT1) protein expression was determined using brush border membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in pancreatic β-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1 expression were determined in streptozotocin (STZ)-induced diabetic mice.Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with the IC50value of 345 μg/mL. SGLT1 protein expression was dose dependently down regulated with EC treatment. Furthermore, insulinotrophic effect of EC extract was observed at high glucose media in isolated pancreatic β-islet cellsin vitro. We next conducted the antihyperglycemic effect of EC in STZ-diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC treatment in diabetic mice. As a result, EC supplementation improved postprandial glucose regulation, assessed by oral glucose tolerance test, in diabetic mice.Conclusion. These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition.
Cytokines and HCV-Related Disorders
Authors: Fallahi Poupak , Ferri Clodoveo , Ferrari Silvia Martina , Corrado Alda , Sansonno Domenico , Antonelli Alessandro
Published: May 2012

Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses. However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-gamma-inducible CXC chemokine ligand (CXCL)-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.
A Generalized q‐Mittag‐Leffler Function by q‐Captuo Fractional Linear Equations
Authors: Abdeljawad Thabet , Benli Betül , Baleanu Dumitru
Published: May 2012

Some Caputo q‐fractional difference equations are solved. The solutions are expressed by means of a new introduced generalized type of q‐Mittag‐Leffler functions. The method of successive approximation is used to obtain the solutions. The obtained q‐version of Mittag‐Leffler function is thought as the q‐analogue of the one introduced previously by Kilbas and Saigo (1995).
Surgical Approach and Laser Applications in BRONJ Osteoporotic and Cancer Patients
Authors: Vescovi Paolo , Merigo Elisabetta , Meleti Marco , Manfredi Maddalena , Fornaini Carlo , Nammour Samir
Published: May 2012

Bisphosphonates-related Osteonecrosis of the Jaw (BRONJ) has been reported with increasing frequency in literature over last years, but its therapy is still a dilemma. One hundred ninety patients affected by BRONJ were observed between January 2004 and November 2011 and 166 treated sites were subdivided in five groups on the basis of the therapeutical approach (medical or surgical, traditional or laser-assisted approach, with or without Low Level Laser Therapy (LLLT)). Clinical success has been defined for each treatment performed as clinical improvement or complete mucosal healing. Combination of antibiotic therapy, conservative surgery performed with Er:YAG laser and LLLT applications showed best results for cancer and noncancer patients. Nonsurgical approach performed on 69 sites induced an improvement in 35 sites (50.7%) and the complete healing in 19 sites (27.5%), while surgical approach on 97 sites induced an improvement in 84 sites (86.6%) and the complete healing in 78 sites (80.41%). Improvement and healing were recorded in 31 (81.5%) and 27 (71.5%) out of the 38 BRONJ sites treated in noncancer patients and in 88 (68.75%) and in 69 (53.9%) out of the 128 in cancer patients.
Thermodynamic and Isotherm Analysis on the Removal of Malachite Green Dye Using Thespesia Populnea Bark
Authors: Prabakaran R. , Arivoli S.
Published: May 2012

Activated carbon was synthesized from Thespesia Populnea Bark, a low cost material, by sulphuric acid activation; it was tested for its ability to eliminate malachite green in aqueous solution. The parameters studied included contact time, initial dye concentration, carbon dose, pH and temperature. The adsorption followed first order rate equation. In addition, it was found that the adsorption process was described by Freundlich and Langmuir isotherm models. Those models were applied to the equilibrium data. The absorption capacities (Qm) obtained from the Langmuir isotherm plots were 349.20, 365.43, 476.44, and 389.96 mg/g at 30°, 40°, 50°, and 60°C, respectively, at an initial pH 6.0. The temperature variation study showed that the malachite green dye absorption was endothermic and spontaneous with increased randomness at the solid solution interface. The thermodynamic parameters like ∆H°, ∆S°, and ∆G° were calculated from the slope and intercept of the linear plots.
Reconstruction of Riser Profiles by an Underwater Robot Using Inertial Navigation
Authors: Menegaldo Luciano Luporini , Panzieri Stefano , Neves Cassiano
Published: May 2012

This paper proposes a kinematic model and an inertial localization system architecture for a riser inspecting robot. The robot scrolls outside the catenary riser, used for underwater petroleum exploration, and is designed to perform several nondestructive tests. It can also be used to reconstruct the riser profile. Here, a realistic simulation model of robot kinematics and its environment is proposed, using different sources of data: oil platform characteristics, riser static configuration, sea currents and waves, vortex-induced vibrations, and instrumentation model. A dynamic finite element model of the riser generates a nominal riser profile. When the robot kinematic model virtually scrolls the simulated riser profile, a robot kinematic pattern is calculated. This pattern feeds error models of a strapdown inertial measurement unit (IMU) and of a depth sensor. A Kalman filter fuses the simulated accelerometers data with simulated external measurements. Along the riser vertical part, the estimated localization error between the simulated nominal and Kalman filter reconstructed robot paths was about 2 m. When the robot model approaches the seabed it assumes a more horizontal trajectory and the localization error increases significantly.
InterconnectedTiO2Nanowire Networks for PbS Quantum Dot Solar Cell Applications
Authors: Xu Fan , Benavides Jaime , Ma Xin , Cloutier Sylvain G.
Published: May 2012

We present a simple method for the fabrication of an interconnected porousTiO2nanostructured film via dip coating in a colloidal suspension of ultrathinTiO2nanowires followed by high-temperature annealing. The spheroidization of the nanowires and the fusing of the loosely packed nanowire films at the contact points lead to the formation of nanopores. Using this interconnectedTiO2nanowire network for electron transport, a PbS/TiO2heterojunction solar cell with a large short-circuit current of 2.5 mA/cm2, aVocof 0.6 V, and a power conversion efficiency of 5.4% is achieved under 8.5 mW/cm2white light illumination. Compared to conventional planarTiO2film structures, these results suggest superior electron transport properties while still providing the large interfacial area between PbS quantum dots andTiO2required for efficient exciton dissociation.
General Switch-and-Stay Combing for Space Diversity over Rayleigh Fading Channels
Authors: Chau Yawgeng A. , Chen Yao-Hua
Published: May 2012

Three multibranch switch-and-stay combining (MSSC) schemes are analyzed for Rayleigh fading channels, where different decision statistics for antenna switching (i.e., switch statistic) are used. Letaandrdenote the fading factor and the received baseband signal of a diversity branch, respectively. In contrast to the traditional MSSC that uses the faded signal-to-noise ratio (SNR) of diversity branches as the corresponding switch statistic, to enhance the receiver performance,|r|,|ar|, and a new linear combination of a and|r|are used as switch statistics of the three MSSC schemes, respectively. For performance evaluation, the bit error rate (BER) of BPSK is derived for the three MSSC schemes over both independent-and-identical distributed (i.i.d.) and independent-and-nonidentical distributed (i.n.d.) Rayleigh fading channels. To pursue optimal performance, the locally optimal switch threshold (ST) of each MSSC scheme is obtained for generali.n.d.fading channels. In addition, the locally optimal ST becomes the globally optimal ST fori.i.d.channels. Numerical results based on the analysis and simulations are presented. In contrast to the MSSC overi.i.d.fading channels, we will show that the performance of MSSC schemes can be improved by increasing the number of branches, ifi.n.d.channels are considered.
Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
Authors: Taylor Michael D. , Clewell Harvey J. , Andersen Melvin E. , Schroeter Jeffry D. , Yoon Miyoung , Keene Athena M. , Dorman David C.
Published: May 2012

Recently, a variety of physiologically based pharmacokinetic (PBPK) models have been developed for the essential element manganese. This paper reviews the development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats, nonhuman primates, and adult, pregnant, lactating, and neonatal humans) and relevant risk assessment applications. Each PBPK model incorporates critical features including dose-dependent saturable tissue capacities and asymmetrical diffusional flux of manganese into brain and other tissues. Varied influx and efflux diffusion rate and binding constants for different brain regions account for the differential increases in regional brain manganese concentrations observed experimentally. We also present novel PBPK simulations to predict manganese tissue concentrations in fetal, neonatal, pregnant, or aged individuals, as well as individuals with liver disease or chronic manganese inhalation. The results of these simulations could help guide risk assessors in the application of uncertainty factors as they establish exposure guidelines for the general public or workers.
Medical Gases: A Novel Strategy for Attenuating Ischemia—Reperfusion Injury in Organ Transplantation?
Authors: Siriussawakul Arunotai , Chen Lucinda I. , Lang John D.
Published: May 2012

Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ transplantation. It can lead to early graft nonfunction and contribute to acute and chronic graft rejection. Advanced molecular biology has revealed the highly complex nature of this phenomenon and few definitive therapies exist. This paper reviews factors involved in the pathophysiology of IRI and potential ways to attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and hydrogen sulfide have been increasingly explored as plausible novel medical gases that can attenuate IRI via multiple mechanisms, including microvascular vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we review recent advances in research utilizing inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate on its future applications specific to solid organ transplantation.
All-Fiber DBR-Based Sensor Interrogation System for Measuring Acoustic Waves
Authors: Comanici Maria Iulia , Zhang Lv , Chen Lawrence R. , Gu Xijia , Wang Lutang , Kung Peter
Published: May 2012

We investigate the use of all-fiber distributed Bragg reflector (DBR) lasers for fiber optic sensing. We measure the steady-state strain response and show that it is very similar to that for a simple fiber Bragg grating (FBG). The lasers can be wavelength multiplexed and support multisensor operation without crosstalk. We also verify the principle of wavelength-to-power mapping, which can simplify sensor interrogation. Finally, we demonstrate that all-fiber DBR lasers can be used to detect acoustic waves.
Improving Accuracy for 3D RFID Localization
Authors: Han Jinsong , Zhao Yiyang , Cheng Yan Shun , Wong Tse Lung , Wong Chun Hung
Published: May 2012

Radio Frequency Identification (RFID) becomes a prevalent labeling and localizing technique in the recent years. Deploying indoor RFID localization systems facilitates many applications. Previous approaches, however, are most based on 2D design and cannot provide 3D location information. The lack of one-dimensional information may lead 2D-based systems to inaccurate localization. In this paper, we develop an indoor 3D RFID localization system based on active tag array. In particular, we employ the geometric mean to filter the explicit 3D location information with high accuracy. The experimental results show that our system is efficient in tracking objects and improving the localization accuracy.
Activation of Right Ventral Prefrontal Cortex Using a Predictive Cue during Visual Spatial Orienting of Attentional Processes: An fMRI Study
Authors: Li Chunlin , Wu Jinglong
Published: May 2012

Visual spatial orienting of attention can be investigated with location-cueing paradigms in which a cue provides correct information about the location of the upcoming target. Target detection is facilitated when the target appears at the expected cued location. In this study, we examined the brain activation of the spatial orienting response based on attentional “benefits.” During an fMRI experiment, two types of attentional tasks were used. Both predictive and nonpredictive cues were used and followed by an upcoming target. Behavioral data showed a faster reaction time with the predictive cue when compared with that of the nonpredictive cue. The fMRI results of these two tasks were compared, whereby isolated brain areas activated when the targets appeared at the attended position after a specific spatial expectation was induced by the cue were compared with when equivalent targets appeared after no spatial expectation was induced by the cue. The results showed that the right ventral prefrontal cortex was activated to a similar degree as the dorsal frontoparietal spatial attentional network.
Chitosan-Hyaluronate Hybrid Gel Intraarticular Injection Delays Osteoarthritis Progression and Reduces Pain in a Rat Meniscectomy Model as Compared to Saline and Hyaluronate Treatment
Authors: Patchornik Shachar , Ram Edward , Ben Shalom Noah , Nevo Zvi , Robinson Dror
Published: May 2012

Chitosan-Hyaluronate hybrid gel (CHHG) is a self-forming thermo-responsive hydrogel. The current study was undertaken in order to assess the effect of CHHG on rat's surgically induced osteoarthritis.Methods. Thirteen rats were included in the study. In all rats weight-bearing was assessed using a Linton Incapacitance tester. All rats underwent bilateral medial partial meniscectomy. Four rats received a saline injection in the control knee and a 200-microliter injection of CHHG in the experimental knee. Five rats received a high-molecular weight hyaluronate injection to the control knee and a 200-microliter injection of CHHG in the experimental knee. Four rats underwent the same surgical procedure, allowed to recuperate for seven days and then CHHG and hyaluronate were injected. The animals were followed for 6 weeks. Two weeks after injection of a therapeutic substance the amount of weight-bearing on each knee was evaluated using a Linton Incapacitance meter.Results. Two weeks after induction of osteoarthritis there is less pain in the CHHG-treated knee than in the control-treated knee, as determined using a Lintron Incapacitance meter. After six-weeks the histological appearance of the CHHG-treated knee was superior to that of the controls. This is indicated by thicker cartilage remaining on the medial femoral condyle as well as less cyst formation in the CHHG-treated knee.Discussion. CHHG appears to delay progression of osteoarthritis and lessen pain in a rat surgically-induced knee osteoarthritis model. These results support other published results, indicating that there is an ameliorative effect of chitosan on human and rabbit osteoarthritis.
Magnolol Protects against MPTP/MPP+-Induced Toxicity via Inhibition of Oxidative Stress inIn VivoandIn VitroModels of Parkinson’s Disease
Authors: Muroyama Akiko , Fujita Aya , Lv Cheng , Kobayashi Shota , Fukuyama Yoshiyasu , Mitsumoto Yasuhide
Published: May 2012

The aim of this study is to investigate the role of magnolol in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-) induced neurodegeneration in mice and 1-methyl-4-phenylpyridinium ion-(MPP+-) induced cytotoxicity to human neuroblastoma SH-SY5Y cells and to examine the possible mechanisms. Magnolol (30 mg/kg) was orally administered to C57BL/6N mice once a day for 4 or 5 days either before or after MPTP treatment. Western blot analysis revealed that MPTP injections substantially decreased protein levels of dopamine transporter (DAT) and tyrosine hydroxylase (TH) and increased glial fibrillary acidic protein (GFAP) levels in the striatum. Both treatments with magnolol significantly attenuated MPTP-induced decrease in DAT and TH protein levels in the striatum. However, these treatments did not affect MPTP-induced increase in GFAP levels. Moreover, oral administration of magnolol almost completely prevented MPTP-induced lipid peroxidation in the striatum. In human neuroblastoma SH-SY5Y cells, magnolol significantly attenuated MPP+-induced cytotoxicity and the production of reactive oxygen species. These results suggest that magnolol has protective effects via an antioxidative mechanism in bothin vivoandin vitromodels of Parkinson’s disease.
Smoking Behavior and Exposure to Tobacco Toxicants during 6 Months of Smoking Progressively Reduced Nicotine Content Cigarettes
Authors: Benowitz Neal L. , Dains Katherine M. , Hall Sharon M. , Stewart Susan , Wilson Margaret , Dempsey Delia , Jacob Peyton
Published: May 2012

Background: Recent federal legislation gives the U.S. Food and Drug Administration authority to regulate the nicotine content of cigarettes. A nationwide strategy for progressive reduction of the nicotine content of cigarettes is a potential way to reduce the addictiveness of cigarettes, to prevent new smokers from becoming addicted, and to facilitate quitting in established smokers. We conducted a trial of progressive nicotine content tapering over 6 months to determine the effects on smoking behaviors and biomarkers of tobacco smoke exposure and cardiovascular effects.

Methods: One hundred and thirty-five healthy smokers were randomly assigned to one of two groups. A research group smoked their usual brand of cigarettes followed by five types of research cigarettes with progressively lower nicotine content, each smoked for one month. A control group smoked their own brand of cigarettes for the same period of time.

Results: Nicotine intake, as indicated by plasma cotinine concentration, declined progressively as the nicotine content of cigarettes was reduced. Cigarette consumption and markers of exposure to carbon monoxide and polycyclic aromatic hydrocarbons, as well as cardiovascular biomarkers remained stable, whereas urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) excretion decreased. No significant changes in biomarkers of exposure or cardiovascular effects were observed in controls.

Conclusions: Our data support the proposition that the intake of nicotine from cigarettes of smokers can be substantially lowered without increasing exposure to other tobacco smoke toxins.

Impact: These findings support the feasibility and safety of gradual reduction of the nicotine content in cigarettes. Cancer Epidemiol Biomarkers Prev; 21(5); 761–9. ©2012 AACR.
The Impact of Race and Comorbidity on Survival in Endometrial Cancer
Authors: Olson Sara H. , Atoria Coral L. , Cote Michele L. , Cook Linda S. , Rastogi Radhai , Soslow Robert A. , Brown Carol L. , Elkin Elena B.
Published: May 2012

Background: Poorer survival from endometrial cancer in blacks than in whites is well documented. The aims of this study were to determine whether diabetes, hypertension, or other conditions influence survival and whether accounting for these conditions reduces this racial disparity.

Methods: Using the SEER-Medicare database, we investigated the influence of diabetes, hypertension, and other comorbid conditions on survival in black and white women age ≥66 with endometrial cancer. We used Cox proportional hazards regression to evaluate the influence of comorbidities on survival for blacks and whites separately and to study survival differences between blacks and whites after adjustment for diabetes, hypertension, and other medical conditions, as well as for demographics, tumor characteristics, and treatment.

Results: In both racial subgroups, women with diabetes or other conditions had poorer overall survival, whereas hypertensive black women experienced better survival [HR, 0.74; 95% confidence interval (CI), 0.60–0.92]. For disease-specific survival, diabetes was associated with poorer survival in white women (HR, 1.19; 95% CI, 1.06–1.35) but not in blacks (HR, 0.97; 95% CI, 0.73–1.30); hypertension and other conditions were not significantly related to survival. After adjustment, black women had poorer survival than white women, with HRs of 1.16 (95% CI, 1.05–1.28) for overall and 1.27 (95% CI, 1.08–1.49) for disease-specific survival.

Conclusions: Diabetes influences disease-specific survival in white women but not in blacks. The racial disparity in survival is not explained by the presence of other health conditions.

Impact: Further research should focus on the unknown factors that lead to poorer survival in black women compared with whites. Cancer Epidemiol Biomarkers Prev; 21(5); 753–60. ©2012 AACR.
Body Mass Index and Colon Cancer Screening: A Systematic Review and Meta-Analysis
Authors: Maruthur Nisa M. , Bolen Shari , Gudzune Kimberly , Brancati Frederick L. , Clark Jeanne M.
Published: May 2012

Background: Obesity is associated with increased colon cancer mortality and lower rates of mammography and Pap testing.

Methods: We conducted a systematic review to determine whether obesity is associated with lower rates of colon cancer screening. We searched the PubMed, CINAHL, and Cochrane Library databases. Two investigators reviewed citations, abstracts, and articles independently. Two investigators abstracted study information sequentially and evaluated quality independently using standardized forms. We included all studies in our qualitative syntheses. We used random effects meta-analyses to combine those studies providing screening results by the following body mass index (BMI) categories: Normal, 18.5–24.9 kg/m2 (reference); overweight, 25–29.9 kg/m2; class I obesity, 30–34.9 kg/m2; class II obesity, 35–39.9 kg/m2; and class III obesity, ≥ 40 kg/m2.

Results: Of 5,543 citations, we included 23 articles. Almost all studies were cross-sectional and ascertained BMI and screening through self-report. BMI was not associated with colon cancer screening overall. The subgroup of obese white women reported lower rates of colon cancer screening compared with those with a normal BMI with combined ORs (95% CI) of 0.87 (0.82–0.93), 0.80 (0.65–0.99), and 0.73 (0.58–0.94) for class I, II, and III obesity, respectively. Results were similar among white men with class II obesity.

Conclusions: Overall, BMI was not associated with colon cancer screening. Obese white men and women may be less likely to undergo colon cancer screening compared with those with a normal BMI.

Impact: Further investigation of this disparity may reduce the risk of obesity-related colon cancer death. Cancer Epidemiol Biomarkers Prev; 21(5); 737–46. ©2012 AACR.
Hazard of Recurrence among Women after Primary Breast Cancer Treatment—A 10-Year Follow-up Using Data from SEER-Medicare
Authors: Cheng Lee , Swartz Michael D. , Zhao Hui , Kapadia Asha S. , Lai Dejian , Rowan Paul J. , Buchholz Thomas A. , Giordano Sharon H.
Published: May 2012

Background: Few studies have used SEER-Medicare data to describe recurrence of breast cancer after primary treatment for U.S. women.

Methods: We used SEER-Medicare data to estimate the annual hazard rate (HR) of recurrence for women with breast cancer between 1991 and 1997 with 10 years of follow-up. The Kaplan–Meier method was used to derive the HR. Multivariate Cox proportional hazards model was used to estimate the relative hazard of the recurrence-associated prognostic factors.

Results: Of 20,027 women, 36.8% had recurrence within 10 years, with most of these recurrences (81.9%) occurring within 5 years after diagnosis. Women with stage III cancer showed the highest HR peak and largest magnitude than women with stage I or II disease (both P < 0.01) within the first 5 years. Women with negative tumor hormone receptor status had a higher peak hazard of developing recurrence within the first 5 years (P < 0.01), but the hazards were remarkably lower beyond 5 years of follow-up than in women with positive or unknown hormone receptor status (P > 0.05). Women with poorly differentiated histologic grade tumors showed higher HR in the first 5 years than women with other grades after primary treatment (both P < 0.01). The increased risk of recurrence of breast cancer was associated with advanced stage, moderate and poorly differently grades, and negative hormone receptor status (all P < 0.01).

Conclusion: The HRs of the recurrence are dynamic over 10 years and are markedly determined by prognostic factors at diagnosis.

Impact: Our study suggests that the optimal follow-up may differ among women. Cancer Epidemiol Biomarkers Prev; 21(5); 800–9. ©2012 AACR.
Cigarette Smoking and Renal Cell Carcinoma Risk among Black and White Americans: Effect Modification by Hypertension and Obesity
Authors: Cote Michele L. , Colt Joanne S. , Schwartz Kendra L. , Wacholder Sholom , Ruterbusch Julie J. , Davis Faith , Purdue Mark , Graubard Barry I. , Chow Wong-Ho
Published: May 2012

Background: Incidence of kidney cancer has been increasing over the past three decades, with more rapid increases and higher incidence rates among blacks than whites in the United States. An association between cigarette smoking and renal cell carcinoma (RCC), the most common form of kidney cancer, has been reported for whites, but the association in blacks is less clear.

Methods: The association between smoking and RCC was examined in 1,217 incident cases and 1,235 population controls frequency-matched on age, race, gender, and study site in the Kidney Cancer Study in Detroit, MI, and Chicago, IL.

Results: In white individuals, increasing duration and number of pack-years of both were associated with increased risk of RCCs after adjusting for age, gender, education, study site, body mass index (BMI) and history of hypertension (Ptrend = 0.0002 and Ptrend = 0.002, respectively). Among black individuals, RCC risk increased with duration of smoking (Ptrend = 0.02) but not other measures. Compared with current smokers, RCC risk decreased with increasing years of smoking cessation among both whites and blacks (Ptrend = 0.01 and 0.02, respectively). When examining risk according to hypertension history, associations between smoking and RCC risk were observed only among individuals who reported never having been diagnosed with hypertension. Similarly, cigarette smoking was associated with increased risk of RCCs among nonobese individuals but not among those with BMI ≥ 30 kg/m2.

Conclusion: Our observation that smoking is associated with RCC only in nonobese individuals and those with no history of hypertension are novel findings.

Impact: The complex relationships between RCCs, smoking, hypertension, and obesity require additional confirmation. Cancer Epidemiol Biomarkers Prev; 21(5); 770–9. ©2012 AACR.
Socioeconomic Position and Stage of Cervical Cancer in Danish Women Diagnosed 2005 to 2009
Authors: Ibfelt Else , Kjær Susanne K. , Johansen Christoffer , Høgdall Claus , Steding-Jessen Marianne , Frederiksen Kirsten , Frederiksen Birgitte Lidegaard , Osler Merete , Dalton Susanne Oksbjerg
Published: May 2012

Background: To reduce social disparities in cervical cancer survival, it is important to understand the mechanisms by which social position influence cancer prognosis. We investigated the relations between socioeconomic factors, comorbidity, time since last Papanicolau smear, and stage at diagnosis in Danish women with cervical cancer.

Methods: We identified 1,651 cervical cancer cases diagnosed 2005 to 2009 from the Danish Gynaecological Cancer Database. Date of diagnosis, clinical cancer stage, tumor histology, and treating hospital were retrieved; Pap smear registrations were obtained from the Danish Pathology Register; data on comorbid conditions from the Danish National Patients Register; and data on education, income, and cohabitation from Statistics Denmark. Logistic regression models were used to analyze the relations between socioeconomic factors and cancer stage in a four-step model, with stepwise inclusion of mediators.

Results: The risk for advanced (stage II–IV) compared with early-stage cancer (stage I) was increased for women with short and medium education (OR = 2.40; 1.67–3.45 and 1.76; 1.44–2.16), women living without a partner (OR = 1.31; 1.10–1.55), and older women (OR = 1.07; 1.06–1.08 increase per year). The relations between socioeconomic factors and cancer stage were partly mediated by time since last Pap smear test and to a lesser extent by comorbidity.

Conclusions: Shorter education, living alone, and older age were related to advanced stage cervical cancer, due partly to Pap smear testing and less to comorbidity.

Impact: It is relevant to further investigate how to decrease delay in cervical cancer diagnosis among disadvantaged groups. Cancer Epidemiol Biomarkers Prev; 21(5); 835–42. ©2012 AACR.
Prostate Stem Cell Antigen Polymorphisms and Susceptibility to Gastric Cancer: A Systematic Review and Meta-analysis
Authors: Wang Tao , Zhang Lina , Li Haixin , Wang Bangmao , Chen Kexin
Published: May 2012

Background: Many studies have reported that prostate stem cell antigen (PSCA) polymorphisms (rs2294008 and/or 2976392) are significantly associated with gastric cancer (GC) risk, although the published results are inconsistent. We conducted a systematic review and meta-analysis for relevant literatures to quantitatively evaluate the relationship between PSCA polymorphisms and GC susceptibility.

Methods: Extensive searches were conducted in three databases up to November 1, 2011. ORs and 95% CIs were used to assess the strength of the associations. The data were further stratified by ethnicity, histopathology, subsite, and study design. All of the associations were evaluated with dominant model and recessive model, respectively. Heterogeneity and publication bias were also assessed by Q test, I2, and funnel plot accordingly.

Results: Nine articles including 11 case–control data sets were included, with 10,746 GC cases and 9,158 controls for rs2294008 and 6,060 cases and 4,824 controls for rs2976392. The results showed that risk allele carriers were significantly associated with GC risk compared with nonrisk allele homozygotes. In stratification analyses, these associations remained significant for majority of subgroups except for Caucasians and noncardia tumor in dominant model, and cardia tumor in both dominant and recessive model. Random model was used when heterogeneity among studies was detected. No publication bias was observed.

Conclusions: The two loci of PSCA (rs2294008 and rs2976392) were both significantly associated with GC susceptibility and in linkage disequilibrium.

Impact: More prospective studies on PSCA polymorphisms at multicenters with sufficient sample size and less heterogeneity will be needed for further validations. Cancer Epidemiol Biomarkers Prev; 21(5); 843–50. ©2012 AACR.
Contribution of Screening and Survival Differences to Racial Disparities in Colorectal Cancer Rates
Authors: Lansdorp-Vogelaar Iris , Kuntz Karen M. , Knudsen Amy B. , van Ballegooijen Marjolein , Zauber Ann G. , Jemal Ahmedin
Published: May 2012

Background: Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the United States. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival.

Methods: We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks, aged 50 years and older, from 1975 to 2007 assuming they had: (i) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); (ii) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and (iii) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates.

Results: Differences in screening accounted for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. Thirty-six percent of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little more than 50% of the disparity in CRC mortality between blacks and whites.

Conclusion: Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites.

Impact: Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden. Cancer Epidemiol Biomarkers Prev; 21(5); 728–36. ©2012 AACR.
Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer’s Disease
Authors: Biscaro Barbara , Lindvall Olle , Tesco Giuseppina , Ekdahl Christine T. , Nitsch Roger M.
Published: May 2012

Background: Activated microglia with macrophage-like functions invade and surround β-amyloid (Aβ) plaques in Alzheimer’s disease (AD), possibly contributing to the turnover of Aβ, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of microglia on neurogenesis in brains with Aβ pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1). Results: Minocycline increased the survival of new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as compared to vehicle-treated transgenic littermates, accompanied by improved behavioral performance in a hippocampus-dependent learning task. Both brain levels of Aβ and Aβ-related morphological deficits in the new neurons labeled with GFP-expressing retrovirus were unaffected in minocycline-treated mice. Conclusions: These results suggest a role for microglia in Aβ-related functional deficits and in suppressing the survival of new neurons, and show that modulation of microglial function with minocycline can protect hippocampal neurogenesis in the presence of Aβ pathology.