bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Study on the Potential of Manuka Honey and Platelet-Rich Plasma in Wound Healing
Authors: Sell Scott A. , Wolfe Patricia S. , Spence Andrew J. , Rodriguez Isaac A. , McCool Jennifer M. , Petrella Rebecca L. , Garg Koyal , Ericksen Jeffery J. , Bowlin Gary L.
Published: December 2012

Aim. The purpose of this study was to determine thein vitroresponse of cells critical to the wound healing process in culture media supplemented with a lyophilized preparation rich in growth factors (PRGF) and Manuka honey.Materials and Methods. This study utilized cell culture media supplemented with PRGF, as well as whole Manuka honey and the medical-grade Medihoney (MH), a Manuka honey product. The response of human fibroblasts (hDF), macrophages, and endothelial cells (hPMEC) was evaluated, with respect to cell proliferation, chemotaxis, collagen matrix production, and angiogenic potential, when subjected to culture with media containing PRGF, MH, Manuka honey, and a combination of PRGF and MH.Results. All three cell types demonstrated increases in cellular activity in the presence of PRGF, with further increases in activity seen in the presence of PRGF+MH. hDFs proved to be the most positively responsive cells, as they experienced enhanced proliferation, collagen matrix production, and migration into anin vitrowound healing model with the PRGF+MH-supplemented media.Conclusion. This preliminaryin vitrostudy is the first to evaluate the combination of PRGF and Manuka honey, two products with the potential to increase regeneration individually, as a combined product to enhance dermal regeneration.
Characterization of Maritime Pine Forests with Combination of Simulated P-Band SAR Data and Hyperspectral Data
Authors: Albinet C. , Borderies P. , Gastellu-Etchegorry J. P.
Published: November 2012

This paper describes a sensitivity study performed on simulated radar and optical remote sensing forest data. It presents how the dual model has been built up. The first step is a forest growth model fed with biophysical parameters. The geometrical description is then the input of an optical hyperspectral model, giving reflectance spectra, and a Synthetic Aperture Radar (SAR) model, giving the polarimetric and interferometric observables. As an illustration, the first results obtained by both models outputs are presented, and fusions of these outputs are performed.
A Generalized Gamma Mixture Model for Ultrasonic Tissue Characterization
Authors: Vegas-Sanchez-Ferrero Gonzalo , Aja-Fernandez Santiago , Palencia Cesar , Martin-Fernandez Marcos
Published: December 2012

Several statistical models have been proposed in the literature to describe the behavior of speckles. Among them, the Nakagami distribution has proven to very accurately characterize the speckle behavior in tissues. However, it fails when describing the heavier tails caused by the impulsive response of a speckle. The Generalized Gamma (GG) distribution (which also generalizes the Nakagami distribution) was proposed to overcome these limitations. Despite the advantages of the distribution in terms of goodness of fitting, its main drawback is the lack of a closed-form maximum likelihood (ML) estimates. Thus, the calculation of its parameters becomes difficult and not attractive. In this work, we propose (1) a simple but robust methodology to estimate the ML parameters of GG distributions and (2) a Generalized Gama Mixture Model (GGMM). These mixture models are of great value in ultrasound imaging when the received signal is characterized by a different nature of tissues. We show that a better speckle characterization is achieved when using GG and GGMM rather than other state-of-the-art distributions and mixture models. Results showed the better performance of the GG distribution in characterizing the speckle of blood and myocardial tissue in ultrasonic images.
The Effects of Bariatric Surgery Weight Loss on Knee Pain in Patients with Osteoarthritis of the Knee
Authors: Edwards Christopher , Rogers Ann , Lynch Scott , Pylawka Tamara , Silvis Matthew , Chinchilli Vernon , Mosher Timothy , Black Kevin
Published: December 2012

Studies have shown that osteoarthritis (OA) is highly associated with obesity, and individuals clinically defined as obese (BMI > 30.0 kg/m2) are four times more likely to have knee OA over the general population. The purpose of this research was to examine if isolated weight loss improved knee symptoms in patients with osteoarthritis. Adult patients (n=24; age 18–70; BMI > 35 kg/m2) with clinical and radiographic evidence of knee OA participated in a one-year trial in which WOMAC and KOOS surveys were administered at a presurgery baseline and six and twelve months postsurgery. Statistical analysis was performed using Student's t and Wilcoxon Signed Rank tests. Weight loss six and twelve months following bariatric surgery was statistically significant (P<0.05) compared to presurgery measurements. All variables from both KOOS and WOMAC assessments were significantly improved (P<0.05) when compared to baseline. Isolated weight loss occurring via bariatric surgery resulted in statistically significant improvement in patient’s knee arthritis symptoms at both six and twelve months. Further research will need to be done to determine if symptom relief continues over time, and if the benefits are also applicable to individuals with symptomatic knee arthritis that are overweight but not obese.
Hepatitis B Infection in Microbiology Laboratory Workers: Prevalence, Vaccination, and Immunity Status
Authors: Jha Arun Kumar , Chadha Sanjim , Bhalla Preena , Saini Sanjeev
Published: December 2012

The risk of contracting HBV by health care workers (HCW) is four-times greater than that of general adult population. Studies have demonstrated that vaccine-induced protection persists at least 11 years. High risk groups such as HCWs should be monitored and receive a booster vaccination if their anti-HBsAb levels decrease below 10 mIU/mL. In view of the above this study was undertaken to assess the HBV vaccination of the HCWs and their immunological response. Seventy-two HCWs of the Department of Microbiology, Maulana Azad Medical College, New Delhi, India, were recruited and blood sample was drawn for serological tests (HBSAg, anti-HCV, anti-HBsAb, anti-HBeAb, and anti-HBcAb). Anti-HBs titers of >10 mIU/mL were considered protective. Thirty-four (47.3%) of the participants were completely vaccinated with three doses. 25 (73.5%) of the participants with complete vaccination had protective anti-HBsAb levels as against 8 (53.3%) of those with incomplete vaccination and 9 (39.1%) of those who were not vaccinated at all. One of our participants was acutely infected while 29 participants were susceptible to infection at the time of the study. All HCWs should receive three doses of the vaccine and be monitored for their immune status after every five years. Boosters should be administered to those who become susceptible.
Periodic Solutions of Some Impulsive Hamiltonian Systems with Convexity Potentials
Authors: Chen Dezhu , Dai Binxiang
Published: November 2012

We study the existence of periodic solutions of some second‐order Hamiltonian systems with impulses. We obtain some new existence theorems by variational methods.
Primary Dumbbell-Shaped Lymphoma of the Thoracic Spine: A Case Report
Authors: Meola Antonio , Perrini Paolo , Montemurro Nicola , di Russo Paolo , Tiezzi Giacomo
Published: November 2012

Primary spinal non-Hodgkin’s lymphoma is extremely rare, and the occurrence of spinal dumbbell-shaped lymphoma is exceptional. We present a case of primary spinal dumbbell-shaped lymphoma to clarify the diagnosis and the management of these lesions. A 45-year-old man presented with sensory symptoms for 8 months. Magnetic resonance imaging of the thoracic spine demonstrated a dumbbell-shaped lesion at the D4–D6 level with spinal cord compression and right foraminal extension at D4–D5 level. The patient underwent D4–D6 laminectomy, with a subtotal resection of the mass. Diffuse large B-cell lymphoma was diagnosed in the pathological examination. He underwent local spinal radiotherapy and chemotherapy. Follow-up evaluation at one year demonstrated no evidence of relapse. Although highly unusual, lymphoma should be included in the differential diagnosis for spinal dumbbell-shaped tumours. After surgery and adjuvant therapy a long-term clinical and neuroradiological followup is mandatory.
A Programmable Look-Up Table-Based Interpolator with Nonuniform Sampling Scheme
Authors: Dutra e Silva Júnior Élvio Carlos , Indrusiak Leandro Soares , Alves Finamore Weiler , Glesner Manfred
Published: December 2012

Interpolation is a useful technique for storage of complex functions on limited memory space: some few sampling values are stored on a memory bank, and the function values in between are calculated by interpolation. This paper presents a programmable Look-Up Table-based interpolator, which uses a reconfigurable nonuniform sampling scheme: the sampled points are not uniformly spaced. Their distribution can also be reconfigured to minimize the approximation error on specific portions of the interpolated function’s domain. Switching from one set of configuration parameters to another set, selected on the fly from a variety of precomputed parameters, and using different sampling schemes allow for the interpolation of a plethora of functions, achieving memory saving and minimum approximation error. As a study case, the proposed interpolator was used as the core of a programmable noise generator—output signals drawn from different Probability Density Functions were produced for testing FPGA implementations of chaotic encryption algorithms. As a result of the proposed method, the interpolation of a specific transformation function on a Gaussian noise generator reduced the memory usage to 2.71% when compared to the traditional uniform sampling scheme method, while keeping the approximation error below a threshold equal to 0.000030518.
Seed and Embryo Germination in Ardisia crenata
Authors: Tezuka Takahiro , Yokoyama Hisa , Tanaka Hideyuki , Shiozaki Shuji , Oda Masayuki
Published: December 2012

Ardisia crenata is an evergreen shrub with attractive bright red berries. Although this species is usually propagated by seed, the seeds take a long time to germinate with conventional sowing methods. We investigated the germination capacity of seeds and embryos collected in different months and the effects of seed storage conditions, germination temperature, water permeability of the seed coat, and the endosperm on seed germination. Seeds and embryos collected in late September or later showed good germination rates. Seeds germinated more rapidly after longer periods of storage at low temperature (approximately 5°C), and those stored in dry conditions showed lower emergence frequency than those stored in wet conditions. Seeds germinated at 15–30°C, but not at 5–10°C. Removal of the seed coat enhanced water uptake and seed germination. Seeds with various proportions of the removed seed coat were sown on a medium supplemented with sucrose. The germination frequency increased as the size of the remaining endosperm decreased. However, the opposite results were obtained when seeds were sown on a medium without sucrose. We concluded that the optimal temperature of 25°C is the most critical factor for seed germination in A. crenata.
Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis
Authors: Cavalcanti Yone Vila Nova , Brelaz Maria Carolina Accioly , Lemoine Neves Juliana Kelle de Andrade , Ferraz José Candido , Pereira Valéria Rêgo Alves
Published: November 2012

Host immune response againstMycobacterium tuberculosisis mediated by cellular immunity, in which cytokines and Th1 cells play a critical role. In the process of control of the infection by mycobacteria, TNF-alpha seems to have a primordial function. This cytokine acts in synergy with IFN-gamma, stimulating the production of reactive nitrogen intermediates (RNIs), thus mediating the tuberculostatic function of macrophages, and also stimulating the migration of immune cells to the infection site, contributing to granuloma formation, which controls the disease progression. IFN-gamma is the main cytokine involved in the immune response against mycobacteria, and its major function is the activation of macrophages, allowing them to exert its microbicidal role functions. Different from TNF-alpha and IFN-gamma, IL-10 is considered primarily an inhibitory cytokine, important to an adequate balance between inflammatory and immunopathologic responses. The increase in IL-10 levels seems to support the survival of mycobacteria in the host. Although there is not yet conclusive studies concerning a clear dichotomy between Th1 and Th2 responses, involving protective immunity and susceptibility to the disease, respectively, we can suggest that the knowledge about this responses based on the prevailing cytokine profile can help to elucidate the immune response related to the protection againstM. tuberculosis.
Thermal-Aware Test Schedule and TAM Co-Optimization for Three-Dimensional IC
Authors: Shih Chi-Jih , Hsu Chih-Yao , Kuo Chun-Yi , Li James , Rau Jiann-Chyi , Chakrabarty Krishnendu
Published: November 2012

Testing is regarded as one of the most difficult challenges for three-dimensional integrated circuits (3D ICs). In this paper, we want to optimize the cost of TAM (test access mechanism) and the test time for 3D IC. We used both greedy and simulated annealing algorithms to solve this optimization problem. We compare the results of two assumptions:soft-die modeandhard-die mode. The former assumes that the DfT of dies cannot be changed, while the latter assumes that the DfT of dies can be adjusted. The results show that thermal-aware cooptimization is essential to decide the optimal TAM and test schedule. Blindly adding TAM cannot reduce the total test cost due to temperature constraints. Another conclusion is that soft-die mode is more effective than hard-die mode to reduce the total test cost for 3D IC.
A First Analysis of Metallome Biosignatures of Hyperthermophilic Archaea
Authors: Cameron Vyllinniskii , House Christopher H. , Brantley Susan L.
Published: December 2012

To date, no experimental data has been reported for the metallome of hyperthermophilic microorganisms although their metal requirements for growth are known to be unique. Here, experiments were conducted to determine (i) cellular trace metal concentrations of the hyperthermophilic ArchaeaMethanococcus jannaschiiandPyrococcus furiosus, and (ii) a first estimate of the metallome for these hyperthermophilic species via ICP-MS. The metal contents of these cells were compared to parallel experiments using the mesophilic bacteriumEscherichia coligrown under aerobic and anaerobic conditions. Fe and Zn were typically the most abundant metals in cells. Metal concentrations forE. coligrown aerobically decreased in the order Fe > Zn > Cu > Mo > Ni > W > Co. In contrast,M. jannaschiiandP. furiosusshow almost the reverse pattern with elevated Ni, Co, and W concentrations. Of the three organisms, a biosignature is potentially demonstrated for the methanogenM. jannaschiithat may, in part, be related to the metallome requirements of methanogenesis. The bioavailability of trace metals more than likely has varied through time. If hyperthermophiles are very ancient, then the trace metal patterns observed here may begin to provide some insights regarding Earth's earliest cells and in turn, early Earth chemistry.
Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Barkam Corinna , Kamal Haytham , Dammann Elke , Diedrich Helmut , Buchholz Stefanie , Eder Matthias , Krauter Jürgen , Ganser Arnold , Stadler Michael
Published: December 2012

Valganciclovir (VGC), an oral prodrug of ganciclovir (GCV), has been shown to clear cytomegalovirus (CMV) viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT), apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79%) than non-VGC therapies (69%). The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss) requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients), we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%), we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0–66)) compared to non-VGC (25 days (0–115)), without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.
A Concise and Comprehensive Description of Shoulder Pathology and Procedures: The 4D Code System
Authors: Lafosse Laurent , Van Isacker Tom , Wilson Joseph B. , Shi Lewis L.
Published: December 2012

Background. We introduce a novel description system of shoulder pathoanatomy. Its goal is to provide a comprehensive three-dimensional picture, with an additional component of time; thus, we call it the 4D code.Methods. Each line of the code starts with right versus left and a time designation. The pillar components are recorded regardless of pathology; they include subscapularis, long head of biceps tendon, supraspinatus, infraspinatus, and teres minor. Secondary elements can be added if there is observed pathology, including acromioclavicular joint, glenohumeral joint, labrum, tear configuration, location and extent of partial cuff tear, calcific tendonitis, fatty infiltration, and neuropathy.Results. We provide two illustrative examples of patients which show the ease and effectiveness of the 4D code. With a few simple lines, significant amount of information about patients’ pathology, surgery, and recovery can be easily conveyed.Discussion. We utilize existing validated classification systems for parts of the shoulder and provide a frame work to build a comprehensive picture. The alphanumeric code provides a simple language that is universally understood. The 4D code is concise yet complete. It seeks to improve efficiency and accuracy of the communication, documentation, and visualization of shoulder pathology within individual practices and between providers.
Diagnosis of Early Gastric Cancer by Magnifying Endoscopy with NBI from Viewpoint of Histological Imaging: Mucosal Patterning in terms of White Zone Visibility and Its Relationship to Histology
Authors: Yagi Kazuyoshi , Nozawa Yujiro , Endou Shinsaku , Nakamura Atsuo
Published: December 2012

The diagnosis of early gastric cancer by magnifying endoscopy with NBI is based on two components: microvascular pattern and mucosal pattern. Mucosal patterns are characterized by a whitish edge, which has been named the white zone. Some cancerous areas showing a distinct white zone form clear mucosal patterns, whereas others showing a nondistinct white zone do not form mucosal patterns. The aim of the present study was to clarify the histological differences between these two types of area. In transverse sections of gastric epithelium, the lengths of intervening parts in areas showing a distinct white zone, a nondistinct white zone, and an invisible white zone were measured, and the depths of the crypts in these three types of area were also measured. The intervening parts in areas with a nondistinct or invisible white zone were shorter than those in areas with a distinct white zone (), and the crypts in the former areas were shallower than those in the latter (). Areas in which the intervening part were long and the crypts deep tended to show a distinct white zone, whereas areas with short intervening parts or shallow crypts tended to show a nondistinct or non-visible white zone.
Expression, Purification, and Evaluation of Diagnostic Potential and Immunogenicity of a Recombinant NS3 Protein from All Serotypes of Dengue Virus
Authors: Álvarez-Rodríguez Laura Mónica , Ramos-Ligonio Angel , Rosales-Encina José Luis , Martínez-Cázares María Teresa , Parissi-Crivelli Aurora , López-Monteon Aracely
Published: December 2012

Dengue is one of the major public health concerns in the world. Since all the four serotypes are actively circulating in Mexico, there is a need to develop an efficient diagnosis system to improve case management of the patients. There exist few studies evaluating the use of the NS3 protein as a protective antigen against dengue virus (DENV). In this paper we show the expression of a recombinant NS3 protein from all serotypes of dengue virus (GST-DVNS3-1-4) and report a reliable “in-house detection system” for the diagnosis of dengue infection which was field-tested in a small village (Tezonapa) in the state of Veracruz, Mexico. The fusion proteins were immunogenic, inducing antibodies to be able to recognize to antigens up to a 1 : 3200 dilution. The purified proteins were used to develop an in-house detection system (ELISA) and were further tested with a panel of 239 serum samples. The in-house results were in excellent agreement with the commercial kits withκ=0.934±0.064(95%  CI = 0.808–1.061), andκ=0.872±0.048(95%  CI = 0.779–0.965) for IgM and IgG, respectively. The agreement between the NS1 antigen detection versus the rNS3 ELISA,κ=0.837±0.066(95%  CI = 0.708–0.966), was very good. Thus, these results demonstrate that recombinant NS3 proteins have potential in early diagnosis of dengue infections.
Low Molecular Weight Z-Tetraol Boundary Lubricant Films in Hard Disk Drives
Authors: Waltman R. J. , Deng H.
Published: December 2012

Lower molecular weight Z-Tetraol films exhibit increased mechanical spacing in the slider-disk interface due to a lower z-profile. An increased resistance to lubricant disturbance on the disk surface (e.g., lube moguls) with decreasing film thickness is attributed to an increasing contribution from the polar component of the disjoining pressure. Evaporative loss at temperatures typically encountered in a hard-disk drive also increases with decreasing molecular weight but is strongly dependent on the initial bonded fraction.
Latest Development on Membrane Fabrication for Natural Gas Purification: A Review
Authors: Mohshim Dzeti Farhah , Mukhtar Hilmi bin , Man Zakaria , Nasir Rizwan
Published: December 2012

In the last few decades, membrane technology has been a great attention for gas separation technology especially for natural gas sweetening. The intrinsic character of membranes makes them fit for process escalation, and this versatility could be the significant factor to induce membrane technology in most gas separation areas. Membranes were synthesized with various materials which depended on the applications. The fabrication of polymeric membrane was one of the fastest growing fields of membrane technology. However, polymeric membranes could not meet the separation performances required especially in high operating pressure due to deficiencies problem. The chemistry and structure of support materials like inorganic membranes were also one of the focus areas when inorganic membranes showed some positive results towards gas separation. However, the materials are somewhat lacking to meet the separation performance requirement. Mixed matrix membrane (MMM) which is comprising polymeric and inorganic membranes presents an interesting approach for enhancing the separation performance. Nevertheless, MMM is yet to be commercialized as the material combinations are still in the research stage. This paper highlights the potential promising areas of research in gas separation by taking into account the material selections and the addition of a third component for conventional MMM.
Development and Validation of a Specific Stability Indicating High Performance Liquid Chromatographic Methods for Related Compounds and Assay of Solifenacin Succinate
Authors: Reddy B. V. Rami , Reddy B. Srinivasa , Raman N. V. V. S. S. , Reddy K. Subhash , Rambabu C.
Published: December 2012

Gradient, reverse phase liquid chromatographic methods were developed separately for the related compounds and solifenacin succinate, an active pharmaceutical ingredient used for the treatment of overactive bladder. Gradient LC method was employed for related compounds. The mobile phase‐A contains a 0.01 M phosphate buffer pH: 3.5 ± 0.05 with orthophosphoric acid (88%) and mobile phase‐B contains a mixture of acetonitrile and water in the ratio of 90 : 10(v/v). The flow rate was 1.0 mL/minute, column temperature was kept at 35°C, and detection was monitored at 220 nm. In the developed HPLC method the resolution between solifenacin succinate and its closely eluting impurity, that is, solifenacin N‐oxide was found to be greater than 3.0. The drug was subjected to stress conditions such as hydrolysis, oxidation, photolysis, and thermal degradation. Considerable degradation was found to occur in only oxidative stress condition. Degradation product formed during oxidative stress condition was found to be impurity‐C and it can be identified by LC‐MS. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP‐LC method was validated as per ICH guidelines. We also developed LC‐MS/MS method for determination and identification of these impurities in solifenacin succinate.
Intravenous Methadone for Severe Cancer Pain: A Presentation of 10 Cases
Authors: Lossignol D. , Libert I. , Michel B. , Rousseau C. , Obiols-Portis M.
Published: November 2012

Purpose. Methadone, a synthetic opioid agonist, is an effective alternative to strong opioids (morphine, hydromorphone, oxycodone, and buprenorphine) and is widely available as an oral formulation. Few data have been published so far on the use of intravenous (i.v.) methadone for the management of severe or refractory cancer pain. Methods. We followed 10 consecutives cancer patients with severe pain, treated with IV methadone. All had advanced disease and had already received strong opioids, some in association with ketamine. Pain was assessed at T0, T24 hours, and at the end of the treatment. Results. All patients benefited from the switch to IV methadone with a reduction of pain on VAS after 24 hours (median: 4/10; range 0–5) until the end of the treatment (all cases <3/10). The median starting dose was 100 mg/day (range 20–400) and the final dose remained stable with a median of 100 mg/day (range 27–700). The median duration of IV methadone was 11 days (range 2–59). No cardiac toxicity had been observed. Conclusions. IV methadone is an effective pain relieving alternative for the treatment of severe cancer pain, especially in refractory pain syndrome. Moreover, we did not observe any toxicity (neurological or cardiac) or any other major side effects and the treatment was overall well tolerated. More extensive comparative studies should be planned.
Complementary and Alternative Medicine in the Treatment of Chronic Pelvic Pain in Women: What Is the Evidence?
Authors: Paiva Sara , Carneiro Márcia Mendonça
Published: November 2012

Chronic pelvic pain (CPP) is defined as pain of at least 6 months’ duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.
Nonlinear Response of High Arch Dams to Nonuniform Seismic Excitation Considering Joint Effects
Authors: Akbari Masoomeh , Hariri-Ardebili Mohammad Amin , Mirzabozorg Hasan
Published: December 2012

Nonuniform excitation due to spatially varying ground motions on nonlinear responses of concrete arch dams is investigated. A high arch dam was selected as numerical example, reservoir was modelled as incompressible material, foundation was assumed as mass-less medium, and all contraction and peripheral joints were modelled considering the ability of opening/closing. This study used Monte-Carlo simulation approach for generating spatially nonuniform ground motion. In this approach, random seismic characteristics due to incoherence and wave passage effects were investigated and finally their effects on structural response were compared with uniform excitation at design base level earthquake. Based on the results, nonuniform input leads to some differences than uniform input. Moreover using nonuniform excitation increase, stresses on dam body.
GA201 (RG7160): A Novel, Humanized, Glycoengineered Anti-EGFR Antibody with Enhanced ADCC and Superior In Vivo Efficacy Compared with Cetuximab
Authors: Gerdes Christian A. , Nicolini Valeria Gonzalez , Herter Sylvia , van Puijenbroek Erwin , Lang Sabine , Roemmele Michaela , Moessner Ekkehard , Freytag Olivier , Friess Thomas , Ries Carola H. , Bossenmaier Birgit , Mueller Hans Joachim , Umaña Pablo
Published: December 2012

Purpose: Anti-EGF receptor (EGFR) antibodies and small-molecule tyrosine kinase inhibitors have shown activity in epithelial tumors; however, agents that work by blocking the EGFR growth signal are ineffective when the oncogenic stimulus arises downstream, such as in tumors with KRAS mutations. Antibodies of the IgG1 subclass can also kill tumor cells directly through antibody-dependent cell-mediated cytotoxicity (ADCC), and the efficacy of this is determined by the interaction of the Fc portion of the target cell–bound antibody and Fc receptors present on immune effector cells.

Experimental Design: We report the development of GA201, a novel anti-EGFR monoclonal antibody with enhanced ADCC properties. GA201 was derived by humanization of the rat ICR62 antibody. The Fc region of GA201 was glycoengineered to contain bisected, afucosylated carbohydrates for enhanced binding to FcγRIIIA.

Results: In vitro binding of GA201 to EGFR inhibited EGF ligand binding, EGFR/HER2 heterodimerization, downstream signaling, and cell proliferation to a similar extent as cetuximab. However, GA201 exhibited superior binding to both the low- and high-affinity variants of FcγRIIIA. This resulted in significantly enhanced induction of ADCC compared with cetuximab against both KRAS-wild-type and -mutant tumor cells lines. This enhanced ADCC translated into superior in vivo efficacy in a series of mouse xenograft models. Efficacy of GA201 was further increased when administered in combination with chemotherapy (irinotecan).

Conclusions: These data suggest that GA201 may be more effective than cetuximab in patients with EGFR-positive solid tumors and may also represent a first-in-class treatment of patients with KRAS-mutated tumors. Clin Cancer Res; 19(5); 1126–38. ©2012 AACR.
Milatuzumab-Conjugated Liposomes as Targeted Dexamethasone Carriers for Therapeutic Delivery in CD74+ B-cell Malignancies
Authors: Mao Yicheng , Triantafillou Georgia , Hertlein Erin , Towns William , Stefanovski Matthew , Mo Xiaokui , Jarjoura David , Phelps Mitch , Marcucci Guido , Lee Ly James , Goldenberg David M. , Lee Robert J. , Byrd John C. , Muthusamy Natarajan
Published: December 2012

Purpose: Corticosteroids are widely used for the treatment of B-cell malignancies, including non–Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia; however, this class of drug is associated with undesirable off-target effects. Herein, we developed novel milatuzumab-conjugated liposomes as a targeted dexamethasone carrier for therapeutic delivery in CD74+ B-cell malignancies and explored its effect against the disease.

Experimental Design: The targeting efficiency of milatuzumab-targeted liposomes to CD74+ cells was evaluated in vitro. The effect of CD74-targeted liposomal dexamethasone was compared with free dexamethasone in primary CLL cells and cell lines in vitro. The therapeutic efficacy of CD74-targeted liposomal dexamethasone was evaluated in a Raji-severe combined immunodeficient (SCID) xenograft model in vivo.

Results: Milatuzumab-targeted liposomes promoted selective incorporation of carrier molecules into transformed CD74-positive B cells as compared with CD74-negative T-cells. The CD74-dexamethasone–targeted liposomes (CD74-IL-DEX) promoted and increased killing in CD74-positive tumor cells and primary CLL cells. Furthermore, the targeted drug liposomes showed enhanced therapeutic efficacy against a CD74-positive B-cell model as compared with free, or non-targeted, liposomal dexamethasone in SCID mice engrafted with Raji cells in vivo.

Conclusions: These studies provide evidence and support for a potential use of CD74-targeted liposomal dexamethasone as a new therapy for B-cell malignancies. Clin Cancer Res; 19(2); 347–56. ©2012 AACR.
ARID1A Mutations in Cancer: Another Epigenetic Tumor Suppressor?
Authors: Wu Jennifer N. , Roberts Charles W.M.
Published: December 2012

Although disordered chromatin organization has long been recognized as a feature of cancer, the molecular underpinnings of chromatin structure, epigenetic regulation, and their relationships to transcription are only beginning to be understood. Cancer genome sequencing studies have revealed a novel theme: frequent mutation of epigenetic regulators. Among these, the ARID1A/BAF250A subunit of the SWI/SNF (BRG1-associated factors) chromatin remodeling complex has emerged as recurrently mutated in a broad array of tumor types. We review the genomic and functional data supporting classification of ARID1A as a tumor suppressor.

Significance: Mutations in chromatin remodeling complex genes are increasingly recognized in many cancer types. However, the mechanisms by which chromatin remodeling complexes contribute to gene expression and the cancer phenotype are poorly understood. Understanding how mutation of chromatin remodelers facilitates transformation may offer the potential for development and implementation of novel therapies for cancer. Cancer Discov; 3(1); 35–43. ©2012 AACR.
The CLOCK C3111T Polymorphism Is Associated with Reward Dependence in Healthy Japanese Subjects
Authors: Tsuchimine Shoko , Yasui-Furukori Norio , Kaneda Ayako , Kaneko Sunao
Published: December 2012

Background: The Circadian Locomotor Output Cycles Kaput (CLOCK) T3111C polymorphism has been associated with several psychiatric disorders, including mood disorders and schizophrenia, which are linked to specific personality traits. We investigated the relationship between the personality traits measured by the Temperament and Character Inventory (TCI) and the C3111T polymorphism of the CLOCK gene in healthy Japanese subjects. Methods: The sample population contained 1,092 healthy subjects (age = 27.4 ± 8.7 years) who completed the TCI. Genomic DNA was isolated from whole blood and genotyped using the TaqMan allele-specific assay method. The associations between the gene polymorphisms and TCI scores were evaluated by one-way analysis of variance and multiple regression analysis. We also compared the TCI scores between the C allele carrier (C/T and C/C genotypes) and non-carrier (T/T genotype) groups using Student’s t test. Males and females were analyzed separately. Results: There was no significant association between the C3111T genotype and any TCI score, but multiple regression analyses revealed significant but opposite associations between reward dependence and the C3111T polymorphism in males and females (p = 0.032, β = 0.087 and p = 0.05, β = –0.087, respectively). Similarly, when we compared the TCI scores of CLOCK C3111T C carrier and non-carrier subjects, we found that male C allele carriers had significantly higher reward dependence scores than non-carriers (p = 0.02). Conclusion: Our findings suggest that the CLOCK C3111T polymorphism may affect personality traits in healthy Japanese subjects.
Multimodality Treatment for Early-Stage Hepatocellular Carcinoma: A Bridging Therapy for Liver Transplantation
Authors: Ashoori N. , Bamberg F. , Paprottka P. , Rentsch M. , Kolligs F.T. , Siegert S. , Peporte A. , Al-Tubaikh J.A. , D’Anastasi M. , Hoffmann R.T. , Reiser M.F. , Jakobs T.F.
Published: November 2012

Purpose: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. Materials and Methods: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4–5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. Results: During a median follow-up time of 29 (4.0–95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36 (44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5–37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. Conclusion: We conclude that TACE combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach.
Effect of Ultrasound Treatment on Brain Edema in a Traumatic Brain Injury Model with the Weight Drop Method
Authors: Yoon Soo Han , Kwon Soon Keun , Park So Ra , Min Byoung-Hyun
Published: December 2012

Background: For the treatment of traumatic brain edema, an efficient modality has not yet emerged. There have been many studies to date which have reported the employment of low-frequency ultrasound for blood-brain barrier disruption (BBBD). However, the authors have observed that low-intensity ultrasound increases water permeability without cellular damage in cartilage cells. We have therefore attempted to observe the effects of applying this low-intensity ultrasound to an experimental animal model. Methods: A traumatic brain injury rat model was established according to the weight drop method developing the traumatic brain edema. The degree of BBBD was measured by the changes in the water content and spectrophotometric absorbance of Evans blue dye in the cerebrum after low-frequency ultrasound. Results: The cerebral water content levels showed that the BBBD gradually increased after impact and thereafter decreased after 6 h. After low-frequency ultrasound exposure, the values of water content and spectrophotometric absorbance of Evans blue dye were the lowest at 0 h, and were increased at 2 and 5 h of ultrasonic exposure (after impact). Conclusion: We suggest that traumatic brain edema in the rat model may be alleviated by low-frequency ultrasound, and low-frequency ultrasound might be proposed as a novel treatment modality for brain edema.
TPH1, MAOA, Serotonin Receptor 2A and 2C Genes in Citalopram Response: Possible Effect in Melancholic and Psychotic Depression
Authors: Arias Bárbara , Fabbri Chiara , Gressier Florence , Serretti Alessandro , Mitjans Marina , Gastó Cristóbal , Catalán Rosa , De Ronchi Diana , Fañanás Lourdes
Published: December 2012

Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal. Methods: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD. Results: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F(6, 378) = 2.90; p = 0.009) and melancholic (F(6, 381) = 2.86; p = 0.0097) features. Conclusions: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features.
Assessment of Cognitive Impairments and Seizure Characteristics in Electroconvulsive Therapy with and without Sodium Valproate in Manic Patients
Authors: Haghighi Mohammad , Bajoghli Hafez , Bigdelou Gholamreza , Jahangard Leila , Holsboer-Trachsler Edith , Brand Serge
Published: December 2012

Objectives: The aim of the present study was two-fold: (1) to compare, in a controlled double-blind quasi-randomized clinical trial, treatment improvements, treatment outcome, and cognitive impairments in patients suffering from current manic episodes, while treated with electroconvulsive therapy (ECT) with and without concurrent sodium valproate therapy, and (2) to compare ECT seizure characteristics in patients with and without concurrent sodium valproate therapy. Methods: A total of 40 inpatients (mean age = 31.80 years, SD = 8.06; 75% males) suffering from bipolar disorders and currently in a manic state took part in the study. They were quasi-randomly assigned either to the target (continuation of sodium valproate administration) or to the control group (discontinuation of sodium valproate administration). All patients underwent bifrontal ECT for at least 6 sessions. Improvements and cognitive impairments were assessed, and seizure characteristics (duration, threshold) were also recorded. Results: Manic episodes improved significantly over time, and irrespective of the group (target vs. control group). Cognitive impairments did not alter over time or between groups. Seizure duration did not change over time or between groups. Seizure threshold did not change over time, but was lower in the target than in the control group. Conclusions: Continuing the administration of sodium valproate neither adversely affects, nor enhances cognitive impairments or seizure duration, but reduces seizure threshold during ECT in patients suffering from manic episodes. Moreover, gender appeared to be more strongly associated with cognitive impairment and seizure activity than treatment approaches in these psychiatric conditions.
Effect of Conventional Mouthrinses on Initial Bioadhesion to Enamel and Dentin in situ
Authors: Hannig C. , Gaeding A. , Basche S. , Richter G. , Helbig R. , Hannig M.
Published: November 2012

Aim: The study aimed to investigate the effect of a customary fluoride solution, containing sodium fluoride and amine fluoride, on initial biofilm formation on enamel and dentin in situ compared directly to chlorhexidine. Methods: Bovine enamel and dentin specimens were mounted on maxillary splints carried by 9 subjects. After 1 min of pellicle formation, rinses with tap water (control), chlorhexidine (meridol med CHX 0.2%, GABA) and a fluoride mouthrinse (elmex, GABA) were performed for 1 min. Subsequently, the slabs were carried for another 8 h. The adherent bacteria were determined by DAPI staining, live-dead staining and determination of colony-forming units after desorption; glucan formation was visualized with concanavalin A. Additionally, energy-dispersive X-ray spectroscopy (EDX) analysis of the in situ biofilm layers was conducted, and contact angle measurements were performed. Statistical evaluation was performed by means of the Kruskal-Wallis test followed by the Mann-Whitney U test (p < 0.05). Results: In the control group, significantly higher amounts of adherent bacteria were detected on dentin (4.8 × 106 ± 5.4 × 106 bacteria/cm2) than on enamel (1.2 × 106 ± 1.5 × 106 bacteria/cm2, DAPI). Chlorhexidine significantly reduced the amount of adherent bacteria (dentin: 2.8 × 105 ± 3.4 × 105 bacteria/cm2; enamel: 4.2 × 105 ± 8.7 × 105 bacteria/cm2). Rinses with the fluoride solution also significantly reduced bacterial adherence to dentin (8.1 × 105 ± 1.5 × 106 bacteria/cm2). Fluoride could not be detected by EDX analysis of the biofilms. Fluoride mouthrinsing did not influence the wettability of the pellicle-covered enamel surface. Conclusion: In addition to the reduction of demineralization and antibacterial effects, fluorides inhibit initial biofilm formation on dental hard tissues considerably, especially on dentin.
Prevalence of Chronic Kidney Disease in Patients with Spinal Cord Injuries/Disorders
Authors: Fischer Michael J. , Krishnamoorthi V. Ram , Smith Bridget M. , Evans Charlesnika T. , St. Andre Justin R. , Ganesh Shanti , Huo Zhiping , Stroupe Kevin T.
Published: December 2012

Background and Objectives: Chronic kidney disease (CKD) and spinal cord injury and disorders (SCI/D) are common and costly conditions among Veterans. However, little is known about CKD among adults with SCI/D. Methods: We conducted cross-sectional analyses of Veterans with SCI/D across all VA facilities in 2006. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and categorized by standard eGFR strata. eGFR was calculated in two ways: (a) the Modification of Diet in Renal Disease (MDRD) equation and (b) the MDRD equation + an empirically derived correction factor for SCI/D (MDRD-SCI/D). Logistic regression models were used to examine the relationship between patient characteristics and CKD. Results: Among 9,333 SCI/D Veterans with an available eGFR, the proportion with CKD was substantially higher based on the MDRD-SCI/D equation (35.2%) than based on the MDRD equation (10.2%). In adjusted analyses, while older age (OR for >65 years = 2.53; 95% CI: 2.21–2.89), female sex (OR 2.18; 95% CI: 1.62–2.92), and a non-traumatic cause for injury (OR 1.39; 95% CI: 1.23–1.57) were associated with an increased odds of CKD, black race (OR 0.64; 95% CI: 0.56–0.72) and a duration of injury of ≥10 years (OR 0.76; 95% CI: 0.67–0.86) were associated with a decreased odds of CKD. Diagnostic codes for CKD and nephrology visits were infrequent for SCI/D Veterans with CKD (27.51 and 6.58%, respectively). Conclusion: Using a recently validated version of the MDRD equation with a correction factor for SCI/D, over 1 in 3 Veterans with SCI/D had CKD, which is more than 3-fold higher than when traditional MDRD estimation is used.