bluuebunny/crossref_metadata_2025 huggingface dataset:
Tris(4‐anisyl)phosphine as an Efficient and Practical Reagent for the Synthesis of (E)‐2‐Benzylidenesuccinates
Authors: Jiang Huanfeng , Wang Wei , Liu Weibing , Qiao Chunli
Published: March 2010

Condensation of maleic anhydride or dimethyl maleate with benzylaldehydes controlled by tris(4‐anisyl)‐phosphine to synthesize dimethyl (E)‐2‐benzylidenesuccinates has been systematically investigated. The protocol gives the product with high stereoselectivity in moderate to good yields under mild conditions. A plausible mechanism has been proposed.
MCM‐41 Catalyzed Efficient Regioselective Synthesis of β‐Aminoalcohol under Solvent‐free Conditions
Authors: Heravi Majid M. , Bakhtiari Khadijeh , Alinejhad Hamideh , Saeedi Mina , Malakooti Reihane
Published: March 2010

β‐Aminoalcohols were synthesized in high yields by reaction of epoxides with amines in the presence of MCM‐41 as a green and reusable catalyst under solvent‐free conditions.
Highly Selective Vapor‐Phase Acylation of Veratrole over H3PO4/TiO2‐ZrO2: Using Ethyl Acetate as a Green and Efficient Acylating Agent
Authors: Javad Kalbasi Roozbeh , Abbaspourrad Alireza , Massah Ahmad Reza , Zamani Farzad
Published: March 2010

A simple sol‐gel method with and without surfactant was applied to prepare TiO2‐ZrO2 mixed oxides containing Ti and Zr at a molar ratio of 1:1. Several catalysts containing w=15% –35% H3PO4 were set up using these mixed oxides. The physical and chemical properties of catalysts were investigated by BET, SEM and pyridine adsorption‐desorption. The catalytic performance of each material was determined for the vapor‐phase acylation of veratrole (1,2‐dimethoxybenzene) to 3,4‐dimethoxyacetophenone (3,4‐DMAP), which was found to be the major product of the reaction of veratrole with ethyl acetate, with alkylated products being the minor products. 2,3‐Dimethoxyacetophenone (2,3‐DMAP) was not detected in the product stream. In the best experimental conditions, the alkylated products were less than 0.7%. This reaction may represent an environmentally friendly alternative to use the ethyl acetate as the acylating reagent. The feed molar ratios of veratrole/ethyl acetate were varied over a wide range of 0.1 to 1, and the optimum feed ratio of veratrole/ethyl acetate was 1:3. Space velocity employed in the veratrole acylation reported as WHSV (veratrole) was 1.2 h−1. The acylation reactions were carried out in the temperature range of 423 to 673 K and the optimum H3PO4 content for acylation was w=15%.
Development and Application of Ultra Performance Liquid Chromatography Method to the Quantification of the Biotransformation of Methyl Paraben in Eisenia foetida
Authors: Mincea Manuela , Şerban Simona , Rusu Irina , Talpos̨ Ioan , Ostafe Vasile
Published: March 2010

A simple and quick ultra performance liquid chromatography method (UPLC) has been developed for determination of methyl paraben (MP) and its major metabolites p‐hydroxybenzoic acid (pHBA) and phenol (Phe), following its biotransformations in Eisenia foetida. After different exposure time to paper contact test, the presence of methyl paraben and his biotransformation products in adult earthworms was monitored. Determination of its metabolites was achieved with a BEH (bridged ethane‐silicon hybrid) C18 column (2.1×50 mm i.d., 1.7 µm particle size), using methanol/water/phosphoric acid as mobile phase, under a gradient elution program, and a PDA (photo‐diode array) detection (quantification with MaxPlot in the range 210–400 nm). The absorption of MP did not exceed 30% and in the first 4–6 h after exposure only minute amounts of pHBA and Phe were detected in the worm homogenates. After 48 h of exposures, almost 70% of absorbed MP was already metabolized to Phe and around 20% could be found as pHBA.
Treatment selection for patients with metastatic renal cell carcinoma
Authors: Atkins Michael B. , Choueiri Toni K. , Cho Daniel , Regan Meredith , Signoretti Sabina
Published: March 2010

The availability of approved agents with distinct mechanisms of action has encouraged investigations to identify optimal treatment strategies for specific patients and specific tumor features. Study of tumors from patients treated with interleukin‐2 (IL‐2) has suggested that response was unlikely in patients with tumors with papillary features or low carbonic anhydrase IX (CAIX) expression. A model combining histologic features and CAIX expression separated patients into 2 groups of roughly equal size, with 96% of the responding patients being in the favorable prognostic group. Additional studies have begun to identify molecular features that might predict response to IL‐2 therapy. In contrast, clinical trial data suggest that temsirolimus was relatively more active than interferon in patients with tumors containing non–clear cell features. Furthermore, pathologic examination showed no correlation of response with CAIX expression, but an apparent association with high expression of either phospho‐AKT or phospho‐S6, proteins either upstream or downstream of mammalian target of rapamycin. Preliminary investigations of tumor specimens from patients receiving vascular endothelial growth factor–targeted therapy suggested that high hypoxia‐inducible factor expression might predict response. In addition, response appeared more likely in tumors with mutated or methylated VHL genes; however, substantial antitumor activity was still observed in patients with VHL wild‐type tumors, particularly in patients treated with either sunitinib or axitinib, rather than bevacizumab or sorafenib. Although these data provide some guidance in treatment selection, considerably more research is needed to identify and validate selection models for particular treatment approaches, and to enable rational and optimal utilization of the available treatment options. Cancer 2009;115(10 suppl):2327‐33. © 2009 American Cancer Society.
Combination targeted therapy in advanced renal cell carcinoma
Authors: Sosman Jeffrey , Puzanov Igor
Published: March 2010

Several novel therapies have been approved recently in advanced renal cell carcinoma (RCC). These agents inhibit pathways downstream of loss of the von Hippel‐Lindau gene VHL. They target the vascular endothelial growth factor (VEGF) ligand, VEGF receptor (VEGFR), mammalian target of rapamycin (mTOR), and other potentially important pathways. Even with improvements in survival, disease progresses in all patients. There is a critical need to increase complete responses (now rare). One such strategy is combining several agents to block different levels of the VEGF‐VEGFR axis (vertical blockade). Alternatively, combination of a VEGF‐VEGFR inhibitor with an mTOR inhibitor is attractive. Finally, horizontal blockade of VEGFR with epidermal growth factor receptor and/or platelet‐derived growth factor receptor, all signaling pathways activated by hypoxia‐inducible factor, is another approach. Already trials have revealed difficulties with combination therapy. By combining agents, the toxicity of 1 or both can be enhanced. The authors of this article report their experience with sorafenib plus bevacizumab, which produced increases in hand‐foot syndrome, hypertension, and proteinuria, all known toxic effects. Clinical activity was impressive with 25 responses in 48 patients (52% response rate). Other combinations also required dose reductions (sorafenib with temsirolimus) or were intolerable (sunitinib with temsirolimus or sunitinib with bevacizumab). Unexpected toxicity characterized by microangiopathic hemolytic anemia occurred late in treatment with sunitinib and bevacizumab. Toxicity may be more severe in patients with RCC, who frequently have 1 kidney and poor renal function. Once tolerability for combination regimens has been established, it will be critical to design informative phase 2 trials and address the benefit of combination versus sequential therapy. Cancer 2009;115(10 suppl):2368‐75. © 2009 American Cancer Society.
Novel therapeutics for metastatic renal cell carcinoma
Authors: Hutson Thomas E. , Figlin Robert A.
Published: March 2010

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically during the past few years. Sunitinib malate, sorafenib tosylate, bevacizumab with interferon α, temsirolimus, and everolimus have improved clinical outcomes in randomized phase 3 trials by inhibiting the vascular endothelial growth factor and related pathways. Combinations and sequences of these agents are being evaluated. Other novel agents are in clinical development, some of which target novel pathways not yet exploited as therapy for RCC. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC. Cancer 2009;115(10 suppl):2361‐7. © 2009 American Cancer Society.
Retracted: Immunotherapy of metastatic renal cell carcinoma
Authors: McDermott David F.
Published: March 2010

Renal cell carcinoma (RCC) evokes an immune response, which occasionally has resulted in spontaneous and dramatic remissions. In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been studied. The most consistent antitumor activity has been reported with interferon‒α (IFN‐α) and interleukin‐2 (IL‐2). In recent years, randomized trials have suggested that high‐dose, intravenous bolus IL‐2 is superior in terms of response rate and possibly in terms of response quality to regimens that involve either low‐dose IL‐2 and IFN‐α, intermediate‐ or low‐dose IL‐2 alone, or low‐dose IFN‐α alone. More significantly, investigations associated with those trials suggested that the potential exists for identifying predictors of response (or resistance) and limiting IL‐2 therapy to those patients who hare most likely to benefit. Although the role of low‐dose, single‐agent cytokines is limited, combinations of cytokines with targeted therapy may have merit. Several studies, including 2 completed, large, phase 3 trials of interferon plus bevacizumab versus interferon alone, have demonstrated superior efficacy with the combination regimen compared with cytokine monotherapy and suggested the potential of an additive effect that requires further exploration. For patients who are unlikely to benefit from IL‐2 or who are unable to receive it, the emergence “targeted immunotherapy” offers hope for improved clinical outcome. Improvements in patient selection, novel agents, and combination therapy will be required to optimize the benefits of immunotherapy in metastatic RCC as the list of effective therapies grows. Cancer 2009;115(10 suppl):2298‐305. © 2009 American Cancer Society.
Targeting mTOR in renal cell carcinoma
Authors: Hudes Gary R.
Published: March 2010

The mammalian target of rapamycin (mTOR) is clearly an important therapeutic target for advanced renal cell carcinoma (RCC), although its mechanisms of activation are not completely understood. In first‐line treatment of patients who have both advanced RCC and multiple risk factors for short survival, temsirolimus improves overall survival (OS) compared with interferon. In patients whose tumors have progressed after sunitinib and/or sorafenib therapy, everolimus improves progression‐free survival compared with placebo. Beyond the initial phase 3 studies demonstrating efficacy, many important questions remain in the clinical application of mTOR inhibition and in developing other inhibitors of PI3K/Akt/mTOR signaling. Important objectives of current and future clinical investigations include a more detailed description of the molecular pathology of RCC and identification of potential biomarkers that are predictive of tumor sensitivity to PI3K/Akt/mTOR targeted therapies. This information may identify other groups of RCC patients that are likely to benefit from inhibition of this signaling pathway. Additional questions concern mechanisms by which tumors become resistant to mTOR inhibitor therapy and how such resistance can be defeated. Possible mechanisms include the loss of feedback inhibition of insulin receptor substate/PI3K signaling resulting from the inhibition of mTOR complex 1 by rapamycin analogs and the activating phosphorylation of Akt by mTOR complex 2. Laboratory studies indicate that these resistance mechanisms could be countered by using other targeted agents in combination with mTOR inhibitors. Cancer 2009;115(10 suppl):2313‐20. © 2009 American Cancer Society.
The 2008 European School of Oncology inside Track Conference, “Predictive Modeling in Prostate Cancer”
Authors: Valdagni Riccardo , Scardino Peter T. , Denis Louis
Published: March 2010

The European School of Oncology (ESO) Inside Track Conference, “Predictive Modeling in Prostate Cancer,” the first event ever dedicated to prediction in prostate cancer, was organized in collaboration with the Prostate Program of Milan National Cancer Institute and the American Italian Cancer Foundation in the wonderful scenario of the Excelsior Lido Hotel in Venice on April 17 through 19, 2008. More than 240 participants from 23 countries attended this 3‐day conference, which convened an exceptional group of experts from all over the world whose presentations provided a framework for understanding the state of the art in predictive modeling of prostate cancer and displayed future research trends in the uro‐oncologic community. Cancer 2009;115(13 suppl):3035–8. © 2009 American Cancer Society.
Biomolecular markers of outcome prediction in prostate cancer
Authors: Lopergolo Alessia , Zaffaroni Nadia
Published: March 2010

Prostate cancer has a variable clinical outcome and, therefore, there is a clear need for novel molecular markers that are specifically associated with biologically aggressive disease to improve staging and prognostication and also to provide mechanistic information to facilitate treatment selection. Different candidate biomarkers have been identified that are linked to patient prognosis and/or response to specific treatments. Such molecules are involved in diverse cellular processes (including cell cycle regulation, cell death and apoptosis, signal transduction, cell adhesion, and angiogenesis) within which aberrant activity of several regulatory pathways has been seen in prostate cancer. Although the number of molecular markers continues to grow, mainly because of the advent of high‐throughput methods, more work needs to be done to develop uniform standards for their characterization to enable comparison of markers across studies. Moreover, a rate‐limiting step in the development of molecular markers is large‐scale clinical assessment and their evaluation in the context of prediction model improvement. In fact, thus far, only a few studies have tested and demonstrated whether the addition of new biological markers improves the accuracy of standard clinical models (nomograms) in predicting biochemical progression in patients with clinically localized prostate cancer who underwent radical prostatectomy. Cancer 2009;115(13 suppl):3058–67. © 2009 American Cancer Society.
Predictive models in diagnosing indolent cancer
Authors: Bangma Chris H. , Roobol Monique J. , Steyerberg Ewout W.
Published: March 2010

The early detection of prostate cancer has led to the increased incidence of tumors that are unlikely to become symptomatic during life: so‐called indolent cancers. The ability to predict indolent prostate cancer is needed to avoid over treatment by unnecessary invasive therapies and to select men for active surveillance. For this report, the currently available nomograms that predict these low‐risk tumors were reviewed. Many of these nomograms were based on clinical patient series, thus, their general application is restricted. Those nomograms based on screening series of the general population need further validation before generalized application is feasible. Cancer 2009;115(13 suppl):3100–6. © 2009 American Cancer Society.
Predictive models in external beam radiotherapy for clinically localized prostate cancer
Authors: Roach Mack , Waldman Fred , Pollack Alan
Published: March 2010

Predictive models are being used increasingly in effort to allow physician and patient expectations to be aligned with outcomes that are based on available data. Most predictive models for men who receive external beam radiotherapy for clinically localized prostate cancer are based on Gleason score, clinical tumor classification, and prostate‐specific antigen (PSA) levels. More sophisticated models also have been developed that incorporate treatment‐related variables, such as the dose of radiation and the use of androgen‐deprivation therapy. Most of the predictive models applied to prostate cancer were derived using PSA recurrence rates as the major endpoint, but clinical endpoints have been incorporated increasingly into predictive models. Biomarkers also are increasingly being added to predictive models in an effort to strengthen them. The Radiation Therapy Oncology Group (RTOG) has completed studies on a wide range of markers using tissue from 2 phase 3 trials (RTOG 8610 and 9202). To date, preliminary assessments of p53; DNA ploidy; p16/retinoblastoma 1 protein; Ki‐67; mouse double‐minute p53 binding protein homolog; Bcl‐2/Bcl‐2–associated X protein; cytosine, adenine, and guanine repeats; cyclooxygenase‐2; signal transducer and activator of transcription 3; cytochrome P450 3A4; and protein kinase A have been completed. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pretreatment and treatment‐related variables and will improve our ability to predict outcome and select the optimal treatment. Cancer 2009;115(13 suppl):3112–20. © 2009 American Cancer Society.
Genomic approaches to outcome prediction in prostate cancer
Authors: Febbo Phillip G.
Published: March 2010

Prostate cancer remains a common cause of cancer death in men. Applications of emerging genomic technologies to high‐quality prostate cancer models and patient samples in multiple contexts have made significant contributions to our molecular understanding of the development and progression of prostate cancer. Genomic analysis of DNA, RNA, and protein alterations allows for the global assessment of this disease and provides the molecular framework to improve risk classification, outcome prediction, and development of targeted therapies. In this review, the author focused on highlighting recent work in genomics and its role in evaluating molecular modifiers of prostate cancer risk and behavior and the development of predictive models that anticipate the risk of developing prostate cancer, prostate cancer progression, and the response of prostate cancer to therapy. This framework has the exciting potential to be predictive and to provide personalized and individual treatment to the large number of men diagnosed with prostate cancer each year. Cancer 2009;115(13 suppl):3046–57. © 2009 American Cancer Society.
Beta‐2‐microglobulin is an independent predictor of progression in asymptomatic multiple myeloma
Authors: Rossi Davide , Fangazio Marco , De Paoli Lorenzo , Puma Alessia , Riccomagno Paola , Pinto Valeria , Zigrossi Paola , Ramponi Antonio , Monga Guido , Gaidano Gianluca
Published: March 2010

BACKGROUND:

Although serum beta‐2 microglobulin (B2M) represents a key variable for symptomatic multiple myeloma (MM) prognostication, its role in predicting the risk of progression of asymptomatic MM to symptomatic disease has not been explored.

METHODS:

This study was bases on a consecutive series of 148 patients with asymptomatic MM and explored the cumulative probability of progression to symptomatic MM as the primary endpoint.

RESULTS:

In univariate analysis, a serum B2M level >2.5 mg/L was associated with an increased probability of disease progression (5‐year risk, 64.5%;P< .001) along with serum monoclonal component (sMC) (P< .001), urinary monoclonal component (uMC) (P< .001), and bone marrow plasma cells (BMPCs) (P< .001). In multivariate analysis, serum B2M was selected as an independent predictor of progression (hazard ratio, 3.30;P= .002). Serum B2M was combined with sMC, uMC, and BMPC to create a risk‐stratification model based on 4 groups with different risk of progression: very low (5‐year risk, 0%), low‐intermediate (5‐year risk, 19.6%), high‐intermediate (5‐year risk, 60.7%), and high (5‐year risk, 80.7%). The model that included serum B2M along with sMC, uMC, and BMPC was able to predict disease progression better than the model that was based on sMC, uMC, and BMPC without serum B2M (C statistics, 0.760 vs 0.726).

CONCLUSIONS:

The current results indicated that 1) serum B2M is an independent predictor of asymptomatic MM progression, and 2) serum B2M adds prognostic information when combined with the most widely used prognosticators of asymptomatic MM progression. Cancer 2010. © 2010 American Cancer Society.
A Waste‐Derived Biosurfactant for the Preparation of Templated Silica Powders
Authors: Boffa Vittorio , Perrone Daniele G. , Montoneri Enzo , Magnacca Giuliana , Bertinetti Luca , Garlasco Luisa , Mendichi Raniero
Published: March 2010

A polymeric anionic biosurfactant isolated from urban bio‐wastes was used as a template for fabricating silica powders of pore size ranging from 4 to 30 nm by the sol‐gel reaction of tetraethylorthosilicate and 3‐aminopropyltriethoxysilane at pH 5. The morphology of the synthesized silica powders was found to depend on the size and the conformation of the biosurfactant molecules or aggregates in solution. The use of waste‐derived biosurfactants as templating agents reduces the fabrication costs and the environmental impact of mesoporous materials. At the same time, it encourages the upgrade of bio‐wastes from a costly disposal matter to a source of chemicals and therefore, of revenue.
Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: A pilot study on a series of 56 patients
Authors: Matarraz Sergio , López Antonio , Barrena Susana , Fernandez Carlos , Jensen Evan , Flores‐Montero Juan , Rasillo Ana , Sayagues José María , Sánchez Maria Luz , Bárcena Paloma , Hernandez‐Rivas Jesús María , Salvador Carlos , Fernandez‐Mosteirín Nuria , Giralt Manuel , Perdiguer Luis , Laranjeira Paula , Paiva Artur , Orfao Alberto
Published: March 2010

A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD34+ cells and/or other major subsets of CD34− cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping.

Methods:

We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease.

Results:

Although MDS‐associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low‐ versus high‐grade cases. The most informative prognostic factors included the number of CD34+ cells, presence of aberrant CD34−/CD117+ precursors, decreased mature neutrophils and CD34− erythroid precursors, and increased numbers of CD36−/lo erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival.

Conclusions:

Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival. © 2010 Clinical Cytometry Society
ICI problem and compensation in MIMO SC‐FDMA system with SC‐SFBC scheme
Authors: Zhang Xiu Pei , Ryu Heung‐Gyoon
Published: March 2010

In this paper, we address the ICI (intercarrier interference) problem and compensation in MIMO (multiple input multiple output) SC‐FDMA (single carrier frequency division multiple access) system that exploits SC‐SFBC (single carrier‐space frequency block coding) scheme. Recently, SC‐FDMA technique has received more attention due to the low PAPR (peak to average power ratio) property. However, SC‐FDMA system is sensitive to phase noise and CFO (carrier frequency offset) which is unavoidable in wireless communication systems. Phase noise and CFO introduce CPE (common phase error) as well as ICI into the received signal and seriously degrade the system performance. Therefore, analysis and suppression of these interferences are of great importance. In this paper, we analyze the interferences in MIMO SC‐FDMA system with SC‐SFBC. Then a new ICI estimation and suppression method is proposed to suppress the interferences. Instead of directly estimating the CFO and phase noise, which is pretty difficult and complex, this algorithm exploits block‐type pilots, which is a common pilot pattern in wireless communication systems, such as LTE standard, to estimate the interferences. After that the interferences are suppressed by the inverse matrix method. Simulation results show that the system performance is significantly improved. Copyright © 2010 John Wiley & Sons, Ltd.
Safety and tolerability of once‐daily extended release quetiapine fumarate in acute schizophrenia: pooled data from randomised, double‐blind, placebo‐controlled studies
Authors: Meulien Didier , Huizar Karin , Brecher Martin
Published: March 2010

Introduction

Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once‐daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication.

Methods

The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double‐blind, placebo‐controlled, randomised studies with quetiapine IR as a reference treatment.

Results

The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR.

Conclusions

The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose‐titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd.
Changes in medication practices for hospitalized psychiatric patients: 2009 versus 2004
Authors: Centorrino Franca , Ventriglio Antonio , Vincenti Alessio , Talamo Alessandra , Baldessarini Ross J.
Published: March 2010

Background

We tested the hypothesis that combinations and total daily doses of psychotropics for hospitalized patients diagnosed with major psychiatric disorders are rising.

Methods

We evaluated McLean Hospital records of 481 consecutive inpatients with DSM‐IV schizophrenia, schizoaffective, or bipolar disorders in 2004 (n = 278) or 2009 (n = 203) to compare characteristics and treatments.

Results

In 2009, Clinical Global Impression (CGI)‐severity scores were 6% lower at intake and improved 1.7 times more than in 2004, as hospitalization‐length decreased by 12%. Polytherapy (≥ 2 psychotropics) increased in 2009 (affective or schizoaffective disorders > schizophrenia). Total psychotropics/patient (3.1–3.2) remained stable but mood‐stabilizers/patient increased markedly and antipsychotics/patient decreased somewhat in 2009. Antipsychotic‐choice (2009) ranked: quetiapine, aripiprazole, risperidone, and others; mood‐stabilizers ranked: lamotrigine, valproate, lithium, and others (1/4 off‐label). In 2009, final total antipsychotic doses (mg/day) increased by 97%, and mood‐stabilizers by 75%. Adverse‐effect rates fell by half. Factors differing independently for 2009 versus 2004 ranked: (a) more CGI improvement, (b) more mood‐stabilizers/patient, (c) lower admission CGI scores, and (c) higher total antipsychotic dose.

Comment

Combinations and doses of antipsychotic and mood‐stabilizing drugs for inpatients increased markedly (2004 vs. 2009) without consistent correspondence of agents/person and doses, without apparent increase in major adverse effects, and with possibly superior clinical improvement. Copyright © 2010 John Wiley & Sons, Ltd.
Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo‐controlled pilot study
Authors: Quante Arnim , Zeugmann Sara , Luborzewski Alexander , Schommer Nicole , Langosch Jens , Born Christoph , Anghelescu Ion , Wolf Juergen
Published: March 2010

Objective

The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo‐controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet.

Methods

In this prospective, double‐blind, placebo‐controlled, randomized trial, 23 inpatients with bipolar depression according to DSM‐IV criteria were included. Before randomization, patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week. After inclusion, all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks. The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale (HDRS) within 6 weeks.

Results

After 6 weeks of treatment, the HDRS score decreased in both groups. There was no significant difference between both the groups at any point of time with respect to the HDRS.

Conclusions

Derived from this small pilot study, adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression. However, this lack of additional benefit seems to stem from the already good effectiveness of the control group, namely the treatment with citalopram. Copyright © 2010 John Wiley & Sons, Ltd.
Association of BDNF Val66Met polymorphism with both baseline HRQOL scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine
Authors: Zou Yan‐Feng , Wang Yu , Liu Ping , Feng Xiao‐Liang , Wang Bin‐Yan , Zang Tong‐Hua , Yu Xin , Wei Jing , Liu Zhong‐Chun , Liu Ying , Tao Ming , Li Hui‐Chun , Li Ke‐Qing , Hu Jian , Li Ming , Zhang Ke‐Rang , Ye Dong‐Qing , Xu Xi‐Ping
Published: March 2010

Objective

To explore the association of brain‐derived neurotrophic‐factor (BDNF) Val66Met polymorphism with both baseline health related quality of life (HRQOL) scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine.

Methods

Patients with major depressive disorder (MDD) took fluoxetine (20 mg/day) for 6 weeks. The HRQOL was measured with the Medical Outcomes Study Short Form‐36 (SF‐36) at baseline and at 6th week. Patients were genotyped for Val66Met polymorphism of BDNF gene.

Results

There was a significant association between social function (SF) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had better SF (compared with Val/Val P = 0.004; compared with Val/Met P = 0.005). A significant association was found between improvement in SF and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in SF (compared with Val/Val P = 0.010; compared with Val/Met P = 0.001). Similar association was found between improvement in mental component summary (MCS) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in MCS (compared with Val/Val P = 0.066; compared with Val/Met P = 0.006).

Conclusions

These results indicate that there may be association between BDNF Val66Met polymorphism and both baseline HRQOL (SF) scores and improvement in HRQOL (SF, MCS) scores in Chinese major depressive patients treated with fluoxetine. Copyright © 2010 John Wiley & Sons, Ltd.
Neurocognition and its influencing factors in the treatment of schizophrenia—effects of aripiprazole, olanzapine, quetiapine and risperidone
Authors: Riedel M. , Schennach‐Wolff R. , Musil R. , Dehning S. , Cerovecki A. , Opgen‐Rhein M. , Matz J. , Seemüller F. , Obermeier M. , Engel R. R. , Müller N. , Möller H.‐J. , Spellmann I.
Published: March 2010

Background

To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment.

Methods

Data were obtained from patients with an acute episode of schizophrenia participating in two double‐blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed.

Results

A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition.

Conclusion

The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine. Copyright © 2010 John Wiley & Sons, Ltd.
NK depletion results in increased CCL22 secretion and Treg levels in Lewis Lung Carcinoma via the accumulation of CCL22‐secreting CD11b+CD11c+ cells
Authors: Mailloux Adam W. , Clark Anna‐Maria A. , Young M. Rita I.
Published: March 2010

Tumor‐induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T‐cells (Tregs). Previous studies demonstrated that NK‐dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK‐derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC‐bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK‐depleted LLC‐bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22‐producing cellular fractions in LLC‐bearing lungs. A novel CD11b+CD11c+ cell population was identified that accumulates in large numbers in NK‐depleted LLC‐bearing lung tissue. These CD11b+CD11c+ cells secreted large amounts of CCL22 that may overcompensate for the loss of NK‐derived CCL22 in the lungs of NK‐depleted LLC‐bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC‐bearing lungs.
Biomedical research of novel biodegradable copoly(amino acid)s based on 6‐aminocaproic acid and L‐proline
Authors: Zhang Weipeng , Shao Jianmin
Published: March 2010

The biomedical properties of novel biodegradable copoly(amino acid)s based on 6‐aminocaproic acid and L‐proline were analyzed in this article. The cytotoxicity of the copolymer films was tested in vitro using human embryonic kidney (HEK) 293 cells. The cell proliferation, cell cycle, cell apoptosis, and hemolysis of the polymers were also investigated. No significant cytotoxic response was detected statistically by cytotoxicity assay, and the results of cell apoptosis and cell cycle showed that there were no statistically significant differences in them. Generally, the cells spread and grew well on polymer film. Meanwhile, the extent of hemolysis on the polymers was acceptable. Evaluation of cytotoxicity by cell cycle and apoptosis as a supplementary assay is correspondingly discussed in this article. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Collagen supramolecular and suprafibrillar organizations on osteoblasts long‐term behavior: Benefits for bone healing materials
Authors: Vigier Sylvain , Helary Christophe , Fromigue Olivia , Marie Pierre , Giraud‐Guille Marie‐Madeleine
Published: March 2010

This study compares the behavior of osteoblastic cells seeded on three structurally distinct collagen‐based materials. Adhesion and long‐term behavior were evaluated in vitro in regard to collagen scaffolds forming loose or dense fibrillar networks or exempt of fibrils. In this purpose collagen solutions at concentrations of 5 and 40 mg/mL were processed by freeze‐drying or by sol/gel fibrillogenesis to form either sponges or hydrogels. Macroscopic and microscopic images of sponges showed a light material exhibiting large pores surrounded by dense collagen walls made of thin unstriated microfibrils of 20 nm in diameter. In comparison collagen hydrogels are more homogeneous materials, at 5 mg/mL the material consists of a regular network of cross‐striated collagen fibrils of 100 nm in diameter. At 40 mg/mL the material appears stiffer, the ultrastructure exhibits cross‐striated collagen fibrils packed in large bundles of 300–800 nm of width. Human osteoblastic cells seeded on top of the 5 mg/mL matrices exhibit a squared shaped osteoblast‐like morphology over 28 days of culture and express both alkaline phosphatase and osteocalcin. Osteoblastic cells seeded on top of sponges or of 40 mg/mL matrices exhibit both flat and elongated resting‐osteoblast morphology. Osteoblastic cells have mineralized the three collagen‐based materials after 28 days of culture but collagen sponges spontaneously mineralized in absence of cells. These results highlight, in an in vitro cell culture approach, the benefit of fibrils and of dense fibrillar networks close to in vivo‐like tissues, as positive criteria for new bone tissue repair materials. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
A cross‐linking model for estimating Young's modulus of artificial bone tissue grown on carbon nanotube scaffold
Authors: PourAkbar Saffar Kaveh , Arshi Ahmad Reza , JamilPour Nima , Najafi Ahmad Raeisi , Rouhi Gholamreza , Sudak Les
Published: March 2010

Carbon nanotubes (CNTs) provide a suitable environment for growth and proliferation of bone cells. The elastic properties exhibited by CNTs can enhance mechanical characteristics of bone mineral phase, hydroxyapatite (HAp), precipitated on such a scaffold. In this article, a simplified model for estimating the axial Young's modulus of a representative volume element (RVE) of CNT‐HAp composite is presented. The model is based on the idea of HAp formation on functionalized sites on CNTs as cross‐links between HAp matrix and CNT. Modeling results show that the reinforcement role contributed by CNT in the RVE causes a significant increase in the Young's modulus of the composite material which is a direct consequence of transferring stresses from the HAp matrix to the CNT through the cross‐links. Similar conclusions may be suggested regarding the improvement of overall mechanical properties of the material. The prediction made by the model lies reasonably well within the limits proposed by conventional Rule‐of‐Mixtures, and sliding below Voigt's model. The Young's modulus predicted by the model lies adjacent to the Hashin‐Shtrikman upper bound as a function of the RVE length (or equivalently CNT aspect ratio). The model simulation indicates that an increase in the CNT aspect ratio and/or number of cross‐links in the RVE, results in the prediction to move closer to the estimation made by Voigt as the assumption of perfect bonding between composite phases is approached. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
A zeolite promoted expeditious one‐pot synthesis of 1‐arylmethyl‐4,5‐dihydro‐2‐aryl‐1H‐imidazole
Authors: Pagadala Ramakanth , Meshram Jyotsna S. , Chopde Himani N. , Panyala Nagender Reddy
Published: March 2010

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A series of 1‐arylmethyl‐4,5‐dihydro‐2‐aryl‐1H‐imidazoles were synthesized expeditiously in good yields from 1,2‐diaminoethane and aromatic aldehydes in the presence of zeolite under microwave irradiation in the absence of solvent. The resulting substituted imidazoles are characterized by 1H and 13C NMR, elemental analysis, and mass spectral data. J. Heterocyclic Chem., (2010)
Extension of a cascade reaction: Microwave‐assisted synthesis of the GFP chromophore derivatives
Authors: Jia Runhong , Yan Shu , Jiang Bo , Shi Feng , Tu Shu‐Jiang
Published: March 2010

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A facile microwave‐assisted synthesis of imidazol‐5(4H)‐one derivatives is accomplished via reactions of 4‐arylmethylene‐2‐phenyloxazol‐5(4H)‐ones with urea (or ammonium acetate) in ethylene glycol. The cascade reaction is simple to perform and occurs under mild conditions with broad scope of applicability. J. Heterocyclic Chem., (2010).
N‐Substituted pyrrole synthesis by Paal–Knorr condensation using recyclable cationic exchange resin in water
Authors: He Yan‐Hong , Wang Gang‐Qiang , Guan Zhi
Published: March 2010

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Cationic exchange resin has been utilized for the first time as a novel and recyclable heterogeneous catalyst for the synthesis of N‐substituted pyrroles from variety of 1,4‐diketones and aniline. This simple synthesis has been accomplished with excellent yields. The recovered catalyst can be reused for subsequent runs with only a gradual decrease in activity. J. Heterocyclic Chem., (2010).
Synthesis of tetrahetrocyclic systems including pyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidine fused with pyrazole derivatives and isolated with 1,3,4‐oxa‐, thiadiazole, and 1,2,4‐tetrazole derivatives
Authors: El‐Essawy Farag A.
Published: March 2010

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A series of isolated and fused tetracyclic compounds, containing pyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidine linked with 1,3,4‐oxa‐, thiadiazole, 1,2,4‐tetrazole, and pyrazole derivatives were prepared by the reaction of 1,8,10‐trimethyl‐4‐oxo‐1,4‐dihydropyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidine‐3‐carboxylate and some common reagents to provide the product in satisfactory yields. J. Heterocyclic Chem., (2010).
The assay of pterostilbene in spiked matrices by liquid chromatography tandem mass spectrometry and isotope dilution method
Authors: Mazzotti Fabio , Di Donna Leonardo , Benabdelkamel Hicham , Gabriele Bartolo , Napoli Anna , Sindona Giovanni
Published: March 2010

Pterostilbene (trans‐3,5‐dimethoxy‐4‐hydroxystilbene) is an active component found in several plant species, exhibiting important pharmacological properties. A new and reliable method of assaying this phyto compound in various matrices is presented; the assay is based on (1) the selectivity of liquid chromatography (LC) hyphenated with electrospray ionisation (ESI), (2) the specificity of a two‐step mass spectrometric analysis (MS/MS) and (3) the accuracy of the isotope dilution method. The labelled analogue may be conveniently synthesised in a few steps. The sensitivity of the method is confirmed by the very low limit of detection (LOD) and limit of quantitation (LOQ) values achieved in the assay of pterostilbene in two distinct fortified matrices, and is further supported by the observed accuracy values. Copyright © 2010 John Wiley & Sons, Ltd.
Recovery of logbooks and international marine data: the RECLAIM project
Authors: Wilkinson Clive , Woodruff Scott D. , Brohan Philip , Claesson Stefan , Freeman Eric , Koek Frits , Lubker Sandra J. , Marzin Catherine , Wheeler Dennis
Published: March 2010

The RECovery of Logbooks and International Marine data (RECLAIM) project is a concerted, international effort to facilitate and encourage the recovery—through imaging and digitisation—of archived marine weather observations, platform and instrumental metadata and historical documentation, from many different countries. Non‐instrumental observations of wind and weather have been recorded in ships' logbooks for hundreds of years, augmented by systematic instrumental observations of sea surface and air temperatures, barometric pressure and other meteorological (and oceanographic) elements largely since the mid‐nineteenth century. Once digitised, these data are widely useful for climate studies and other avenues of scientific research—including oceanography, fisheries, maritime history and ecology—thus improvements seeking to address gaps and weaknesses in the currently available data record can be of major importance. In addition to documenting and prioritising archived ship logbook records for imaging and digitisation in support of that goal, RECLAIM provides expert assistance in the interpretation of historical marine records in relation to navigation, observational practices and recording. Since the project inception in 2005, RECLAIM has facilitated, for example, recovery of logbooks of the Dutch and English East India Companies in the nineteenth century, and of the British Royal Navy of the twentieth century. Currently the project website includes reference lists, rescued UK and US marine documents, extensive UK archive reports and detailed inventories of ship movements. A variety of other developing international linkages are discussed, including to Chilean, Dutch, French, German, Finnish, Norwegian, Swedish and US historical records. © Royal Meteorological Society and Crown Copyright 2010.