bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Timing on Efficacy and Safetyof Intracoronary Autologous Bone Marrow Stem Cells Transplantation in Acute Myocardial Infarction: A Pooled Subgroup Analysis of Randomized Controlled Trials
Authors: Zhang Shuning , Sun Aijun , Xu Danling , Yao Kang , Huang Zheyong , Jin Huan , Wang Keqiang , Zou Yunzeng , Ge Junbo
Published: August 2009

Background

Until now there were no clinical studies or systematic reviews to investigate the impact of timing on efficacy and safety of intracoronary bone marrow stem cell (BMSC) transfer in patients with acute myocardial infarction (AMI).

Hypothesis

Timing of BMSC administration might play an important role in the therapeutic response in AMI patients.

Methods

A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence‐Based Medicine (EBM) databases was made on randomized controlled trials with at least 3‐month follow‐up data for patients with AMI undergoing emergent percutaneous coronary intervention (PCI) and receiving intracoronary BMSC transfer thereafter.

Results

A total of 7 trials with 660 patients were available for analysis. Compared to baseline level, BMSC transfer at 4 to 7 days post‐AMI significantly improved left ventricular ejection fraction (LVEF; 4.63% increase, 95% confidence interval [CI]: 1.00%‐8.26%, P = 0.01), reduced left ventricular (LV) end‐systolic dimensions (95% CI: − 0.53 − 0.02, P = 0.03), decreased the incidences of revascularization (odds ratio [OR]: 0.60, 95% CI: 0.37–0.97, P = 0.04), decreased the cumulative clinical events of death or recurrent myocardial infarction (OR: 0.32, 95% CI: 0.11–0.95, P = 0.04), and decreased culprit artery restenosis or ventricular arrhythmia (OR: 0.59, 95% CI: 0.36–0.96, P = 0.03) however these improvements did not reach statistical significance in emergent transfer trials (within 24 hour post‐AMI). Compared with emergent transfer, intracoronary BMSC therapy at 4 to 7 days also significantly reduced the incidence of revascularization (P for interaction = 0.02).

Conclusions

BMSC transfer at 4 to 7 days post‐AMI was superior to that within 24 hours in improving LVEF, decreasing LV end‐systolic dimensions, and reducing the incidence of revascularization. Copyright © 2009 Wiley Periodicals, Inc.
Prophylaxis to Prevent Infective Endocarditis: To Use or Not to Use?
Authors: Dhoble Abhijeet , Vedre Ameeth , Abdelmoneim Sahar S. , Sudini Srikar Reddy , Ghose Amit , Abela George S. , Karve Milind
Published: August 2009

The American Heart Association (AHA) published their revised guidelines in 2007 in which they markedly limited the recommendations for the use of antimicrobial prophylaxis for the prevention of infective endocarditis (IE), except for patients who are at highest risk of adverse outcomes. A recent focused update on valvular heart diseases changed the recommendation for antibiotic use for patients with many underlying heart conditions including mitral valve prolapse (MVP) which were considered as “low risk” heart defects. In this article, we argue that antibiotic prophylaxis should be considered until concrete clinical evidence is provided to dispute against the use of this strategy, especially for patients with MVP. This approach is cost efficient, and provides a chance to prevent a dreadful disease. We have also enlisted 2 clinical cases to support our argument. These are not uncommon clinical scenarios, and emphasize that IE can be fatal in spite of optimum treatment. Patients have the right to make the final decision, and they should be allowed to participate in choosing for or against this approach until adequate clinical evidence is available. Copyright © 2009 Wiley Periodicals, Inc.
Chest Discomfort: A Confusing Symptom
Authors: Richard Conti C.
Published: August 2009

When patients present with chest discomfort, efforts are made to determine whether the symptom is due to myocardial ischemia or something else. Julian, in 1981, suggested that “angina pectoris is a sense of discomfort arising in the myocardium as a result of myocardial ischemia in the absence of infarction.”1 Copyright © 2009 Wiley Periodicals, Inc.
A Virtual Screening Study of the 18 kDa Translocator Protein using Pharmacophore Models Combined with 3D‐QSAR Studies
Authors: Tuccinardi Tiziano , Taliani Sabrina , Bellandi Marusca , Da Settimo Federico , Da Pozzo Eleonora , Martini Claudia , Martinelli Adriano
Published: August 2009

In the present study, we considered various pharmacophore hypotheses for TSPO ligands and an optimal one was selected on the basis of 3D‐QSAR studies. This hypothesis was used in a ligand‐based virtual screening study on the Maybridge database with the aim of identifying new TSPO ligands. Binding assays revealed that all selected compounds displayed TSPO affinity at 10 μM, and among them two compounds exhibited sub‐micromolarKivalues. These results validated our applied methodologies, and the two compounds with sub‐micromolar affinity could be used as interesting leads for the development of new active TSPO ligands.
Role of fine‐needle aspiration cytology in tuberculosis of bone
Authors: Handa Uma , Garg Shailja , Mohan Harsh , Garg Sudhir Kumar
Published: August 2009

This study was designed to evaluate the role of fine‐needle aspiration cytology (FNAC) in diagnosis of skeletal tuberculosis (TB). In this retrospective study, 20 cases were retrieved over a 10‐year period in which a cytologic diagnosis of osseous TB was rendered. The aspirations were performed with a 22‐gauge needle attached on a 20‐ml syringe after taking into consideration the radiological findings. The cytologic findings were subdivided into the following categories—epithelioid cell granulomas with necrosis, epithelioid cell granulomas without necrosis, and necrosis only. These cases were either with or without AFB positivity. The smears showed epithelioid cell granulomas in 23 cases (85.2%), multinucleate and Langhans' giant cells in 15 cases (55.6%), and inflammatory cells were noted in the background in 15 cases (55.6%). AFB was positive in six cases (22.7%). FNA provides a simple and safe outpatient procedure for the diagnosis of osseous TB and obviates the need of an open biopsy. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Comparison of methods trial for high‐risk HPV
Authors: Kurtycz Daniel F. I. , Smith Michele , He Rong , Miyazaki Kayo , Shalkham John
Published: August 2009

In efforts to improve service, we compared the performance of four methods of HPV detection: Invader® HPV (Hologic), Hybrid Capture 2® (Qiagen), Inform® HPV detection (Ventana), and standard PCR.

Using blinded/de‐identified cervical samples in Preservcyt® (Hologic), we compared Ventana's Inform® HPV Test, against Hologic's HPV Invader® and PCR. In a separate evaluation, we compared Inform® versus Invader versus hc2®. Ventana employs in situ hybridization; Hologic's technology uses three specifically designed oligonucleotides and a fluorescent signal for detection. Qiagen's hc2® method incorporates enzyme‐linked antibody detection of RNA–DNA hybrids. PCR testing was provided by Access Genetics (Minneapolis, MN). The United States Food and Drug Administration recently approved the Third Wave/Hologic Invader HPV high‐risk test (rebranded as CervistaTM HPV HR Test).

In this small study, involving a few hundred tests, Third Wave, Qiagen, and PCR tests were comparable. Kappa statistics comparing Third Wave to PCR and Third Wave to Qiagen were 0.88 and 0.74, respectively. Ventana's method did not correlate well with any of the other methods with Kappa's ranging from a low of 0.25 versus Qiagen to 0.31 versus PCR. Kappa statistics measure correlation and not accuracy of measurement.

Although we felt that the specificity of our original HPV method, Ventana Inform® was satisfactory and lowered our subsequent colposcopy rate, worries about its lower sensitivity caused us to look at other techniques. Other methods, PCR, hc2, and Invader®, appeared comparable with one another in our series. We chose to implement the Third Wave test in our laboratory. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Mediastinal epithelioid hemangioendothelioma metastatic to lymph nodes and pleural fluid: Report of a case
Authors: Antic Tatjana , Staerkel Gregg
Published: August 2009

Epithelioid hemangioendothelioma is a rare mesenchymal tumor of vascular origin, classified as a sarcoma of intermediate malignant potential. Involvement of numerous sites of the body, including visceral organs, soft tissue, testis, skeleton, brain, meninges, and skin have been described. We report an unusual case of a mediastinal epithelioid hemangioendothelioma in a 65‐year‐old female initially presenting as a metastasis to lymph nodes of the hilar region and subsequently as a malignant pleural effusion. The patient had a complex history of papillary renal cell carcinoma, papillary thyroid carcinoma, and Waldenstrom's hyperglobulinemia making the diagnosis of metastatic epithelioid hemangioendothelioma difficult. Clinical, cytological and immunohistochemical features of this tumor are described with an emphasis on diagnostic pitfalls. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Value of fine‐needle aspiration biopsy in initial evaluation of floor of the mouth masses: Report of a case of low‐grade mucoepidermoid carcinoma
Authors: David Doina , Clayman Lewis , Saleh Husain
Published: August 2009

Low‐grade mucoepidermoid carcinoma (LG MEC) is a rare tumor which can occur in the minor salivary glands as intraoral lesion, more frequently in the palate and very rarely in the floor of the mouth. Traditionally, the diagnosis has been made on surgical resection specimens only. There is new growing evidence that these lesions can be accurately diagnosed by a fine‐needle aspiration (FNA) biopsy procedure. In this article, we report a case of LG MEC of the floor of mouth diagnosed by FNA and confirmed by subsequent surgical resection. We also provide clues for high index of suspicion for these rare lesions, both clinically and morphologically. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Fasting hyperinsulinemia associates with increased sub‐clinical inflammation in first‐degree relatives normal glucose tolerant women independently of the metabolic syndrome
Authors: Setola Emanuela , Monti Lucilla D. , Lucotti Pietro , Galluccio Elena , Oldani Matteo , Bosi Emanuele , Piatti PierMarco
Published: August 2009

Background

To evaluate the influence of gender on the relationship between inflammation and hyperinsulinemia in first‐degree relatives of type 2 diabetic patients independently of metabolic syndrome.

Methods

Study group consisted in 217 first‐degree relatives with normal glucose tolerance after an oral glucose tolerance test. A logistic analysis, adjusted for age, sex and all the components of the metabolic syndrome, was used to determine the relationship between interleukin‐6 (IL‐6) and leptin and tertiles of fasting insulin, and to take into account the influence of gender.

Results

In the whole cohort, IL‐6 and leptin were significantly higher and adiponectin significantly lower in the III tertile when corrected for age, body mass index (BMI) and metabolic syndrome components. In women, but not in men, IL‐6 and leptin remained significantly higher when corrected for metabolic syndrome. In the whole cohort and in women, univariate correlations between IL‐6 concentrations and the parameters under evaluation showed that IL‐6 and leptin were positively correlated with age, BMI, waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, fasting insulin, ΔAUC insulin area, triglyceride (TG), free fatty acids (FFA) and monocyte chemoattractant protein‐1 (MCP‐1) and inversely correlated with HDL cholesterol (HDL‐C) and adiponectin. In women a forward stepwise linear regression analysis in a model including age, BMI, features of metabolic syndrome, fasting insulin, ΔAUC insulin and insulin sensitivity index (ISI) index revealed that only IL‐6 and leptin were independently associated with fasting insulin levels.

Conclusions

In first‐degree relatives normal glucose tolerant women, fasting hyperinsulinemia, independently of the presence of metabolic syndrome, is associated with elevated IL‐6 and leptin levels, suggesting an increased cardiovascular risk. Copyright © 2009 John Wiley & Sons, Ltd.
Baicalin reduces mitochondrial damage in streptozotocin‐induced diabetic Wistar rats
Authors: Waisundara Viduranga Y. , Hsu Annie , Tan Benny Kwong‐Huat , Huang Dejian
Published: August 2009

Background

Hyperglycemia‐induced superoxide production in the mitochondria is known to be the primary cause of diabetic micro‐ and macro‐vascular complications and mitochondrial membranal damage. This study in streptozotocin‐induced diabetic Wistar rats investigated the anti‐hyperglycemic and mitochondrial membrane protection effects of baicalin, a flavonoid known for its radical scavenging activity.

Methods

The following oral treatments were given to diabetic rats for 30 days: (1) metformin 500 mg/kg, (2) baicalin 120 mg/kg, and (3) metformin 500 mg/kg & baicalin 120 mg/kg, with vehicle‐treated diabetic and non‐diabetic groups serving as controls.

Results

Transmission electron microscopy imaging of pancreatic β‐cells revealed loss of integrity of the inner membrane of the mitochondria in the diabetic rats, which was not observed in the baicalin‐treated group. In addition, baicalin and the combined treatment of metformin and baicalin had significantly reduced (p < 0.05) the number of mitochondria with a damaged membrane compared to the diabetic control as well as the metformin‐treated group in the hepatic tissues. Baicalin had also increased the plasma leptin content (p < 0.05) versus the diabetic control, which in turn had effected the total expression of hepatic mitochondria per cell indicating its effects in SIRT1 activity. The increase in mitochondrial number was further complemented with similar trends in the hepatic citrate synthase activity.

Conclusions

Baicalin had reduced the hyperglycemia‐induced mitochondrial membrane damage, as well as enhanced the effects of metformin, as was observed in the results from the metformin and baicalin treated groups. Copyright © 2009 John Wiley & Sons, Ltd.
Protective role of pigment epithelium‐derived factor (PEDF) in early phase of experimental diabetic retinopathy
Authors: Yoshida Yumiko , Yamagishi Sho‐Ichi , Matsui Takanori , Jinnouchi Yuko , Fukami Kei , Imaizumi Tsutomu , Yamakawa Ryoji
Published: August 2009

Background

Pigment epithelium‐derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy.

Methods

Streptozotocin‐induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8‐hydroxydeoxyguanosine (8‐OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)‐conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence.

Results

Retinal PEDF levels were reduced, and amplitudes of a‐ and b‐wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8‐OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy.

Conclusions

Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase‐driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd.
The protein tyrosine kinase Tec regulates mast cell function
Authors: Schmidt Uwe , Abramova Anastasia , Boucheron Nicole , Eckelhart Eva , Schebesta Alexandra , Bilic Ivan , Kneidinger Michael , Unger Bernd , Hammer Martina , Sibilia Maria , Valent Peter , Ellmeier Wilfried
Published: August 2009

Mast cells play crucial roles in a variety of normal and pathophysiological processes and their activation has to be tightly controlled. Here, we demonstrate that the protein tyrosine kinase Tec is a crucial regulator of murine mast cell function. Tec was activated upon FcεRI stimulation of BM‐derived mast cells (BMMC). The release of histamine in the absence of Tec was normal in vitro and in vivo; however, leukotriene C4 levels were reduced in Tec−/− BMMC. Furthermore, the production of IL‐4 was severely impaired, and GM‐CSF, TNF‐α and IL‐13 levels were also diminished. Finally, a comparison of WT, Tec−/−, Btk−/− and Tec−/−Btk−/− BMMC revealed a negative role for Btk in the regulation of IL‐4 production, while for the efficient production of TNF‐α, IL‐13 and GM‐CSF, both Tec and Btk were required. Our results demonstrate a crucial role for Tec in mast cells, which is partially different to the function of the well‐characterized family member Btk.
Gadd45b and Gadd45g are important for anti‐tumor immune responses
Authors: Ju Songguang , Zhu Yibei , Liu Lin , Dai Shao , Li Changyou , Chen Elizabeth , He Yukai , Zhang Xueguang , Lu Binfeng
Published: August 2009

An effective Th1 type cell‐mediated immune response against cancer cells is critical in limiting cancer progression. Gadd45b, a signaling molecule highly up‐regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b−/− mice grew faster than those in WT or Gadd45b+/− littermate controls. The defect of Gadd45b−/− mice in tumor immunosurveillance was attributed to the reduced expression of IFN‐γ, granzyme B, and CCR5 in Gadd45b−/− CD8+ T cells at the tumor site. Activation of p38 MAP kinase, but not ERK or JNK, by either TCR‐stimuli or IL‐12 and IL‐18 is diminished in Gadd45b−/− CD8+ T cells, resulting in reduced production of IFN‐γ. In addition, mRNA of T‐bet and Eomes were reduced in Gadd45b−/− CD8+ T cells, supporting a critical role of Gadd45b in shaping the Th1 fate. More importantly, the tumor vaccination, which is effective in WT mice, failed in Gadd45b/Gadd45g doubly deficient mice. Collectively, these data demonstrate that members of the Gadd45 gene family are important for anti‐tumor immune responses.
Low cross‐reactivity of T‐cell responses against lipids from Mycobacterium bovis and M. avium paratuberculosis during natural infection
Authors: Van Rhijn Ildiko , Nguyen Thi Kim Anh , Michel Anita , Cooper Dave , Govaerts Marc , Cheng Tan‐Yun , van Eden Willem , Moody D. Branch , Coetzer Jacobus A. W. , Rutten Victor , Koets Ad P.
Published: August 2009

Although CD1 proteins are known to present mycobacterial lipid antigens to T cells, there is little understanding of the in vivo behavior of T cells restricted by CD1a, CD1b and CD1c, and the relative immunogenicity and immunodominance of individual lipids within the total array of lipids that comprise a bacterium. Because bovines express multiple CD1 proteins and are natural hosts of Mycobacterium bovis and Mycobacterium avium paratuberculosis (MAP), we used them as a new animal model of CD1 function. Here, we report the surprisingly divergent responses against lipids produced by these two pathogens during infection. Despite considerable overlap in lipid content, only three out of 69 animals cross‐react with M. bovis and MAP total lipid preparations. The unidentified immunodominant compound of M. bovis is a hydrophilic compound, whereas the immunodominant lipid of MAP is presented by CD1b and was identified as glucose monomycolate (GMM). The preferential recognition of GMM antigen by MAP‐infected cattle may be explained by the higher expression of GMM by MAP than by M. bovis. The bacterial species‐specific nature of the CD1‐restricted, adaptive T‐cell response affects the approach to development of lipid based immunodiagnostic tests.
IL‐2‐inducible T‐cell kinase (ITK) finds another (dance) partner…TFII‐I
Authors: August Avery
Published: August 2009

The signals that regulate T‐cell activation have been studied for some time. We know that upon interaction with antigen/MHC complex, the TCR triggers the activation of a number of kinases, including tyrosine and serine/threonine kinases. The Tec family kinase IL‐2– inducible T‐cell kinase (ITK) plays a role in this response, but the signaling pathways that ITK regulates are less well known. Even less known are the binding partners and substrates of ITK. A paper in this issue of the European Journal of Immunology extends our knowledge on the subject by showing that ITK interacts with the transcriptional regulator TFII‐I. The implications of this finding are discussed.
Fusion of Coordination‐ and Polyoxometalate Chemistry – Chelated Cobalt(III) Centers as Structural Components of Polyoxomolybdates – [{Co(en)}4Mo10O38]4– and Macrocyclic [{CoII(H2O)2}­{Co(en)}8{Mo20O76}]6–
Authors: Belai Nebebech , Kapoor Pramesh N. , Dickman Michael H. , Butcher Raymond J. , Pope Michael T.
Published: August 2009

On the basis of the argument that a monochelated octahedral transition‐metal unit is topologically analogous to the Type II (cis‐dioxo) metal center frequently observed in the structures of many polyoxometalates, we report the synthesis and structural characterization of salts of two polyoxomolybdate anions demonstrating this principle, [{Co(en)}4Mo10O38]4– (1) and [{CoII(H2O)2}{Co(en)}8{Mo20O76}]6– (2). Anion 1 has a structure of nominal Cs symmetry and consists of two blocks of seven edge‐shared metal‐centered octahedra linked by two corner‐shared junctions (Co–O–Mo). The four octahedra which contain {Co(en)}3+ instead of {MoO2}2+ are distributed unequally between the two blocks, three in one and the fourth in the other. The structure of 2 can be described as a chiral macrocyclic assembly (C4 symmetry) of four identical blocks of seven octahedra as observed in the structure of 1, but now containing two {Co(en)}3+ per block. As in 1 the blocks are linked by corner‐shared Co–O–Mo linkages. A trans‐diaquacobalt(II) cation occupies the center of the anion. The opportunities provided by the introduction of chelated metal centers, especially those with unsymmetrical diamines, into new polyoxometalates include the generation of resolvable and optically stable structures that have so far eluded polyoxometalate chemists.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Syntheses of Triostin A Antibiotic and Nucleobase‐Functionalized Analogs as New DNA Binders
Authors: Kumar Ray Anmol , Diederichsen Ulf
Published: August 2009

A total synthesis of the natural product triostin A, wherein the N‐methylated depsipeptide scaffold is constructed by solution‐phase peptide chemistry followed by disulfide formation and macrocyclization, is described. Finally, the quinoxalines were attached to provide the DNA bisintercalator. Analogs of triostin A were obtained by the successive functionalization of the cyclic depsipeptide with pyrimidine or purine recognition units. The attachment of functional units was achieved by the orthogonal protection of the respective side chain amino functionalities. The nucleobase‐functionalized triostin analogs have the potential to recognize double‐stranded DNA by hydrogen bonding. The interaction with DNA was investigated by UV spectroscopy and fluorescence intercalator displacement. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Tetrazoles and para‐Substituted Phenylazo‐Coupled Calix[4]arenes as Highly Sensitive Chromogenic Sensors for Ca2+
Authors: Chen Yu‐Jen , Chung Wen‐Sheng
Published: August 2009

Calix[4]arenes 3a (R = OMe) and 3b (R = NO2) with 5,17‐bis[4‐(4‐substituted‐phenyl)azo] and 25,27‐bisoxymethyltetrazole groups were synthesized by 1,3‐dipolar cycloaddition of oxyacetonitrile azocalix[4]arenes 2a and 2b activated with trimethylsilyl azide. UV/Vis screening of 3a and 3b with 14 metal ions showed that 3a (with p‐methoxyphenylazo substituent) was a highly chromogenic sensor to Ca2+, whereas 3b (with p‐nitrophenylazo substituent) showed color changes toward Ca2+, Ba2+, and Pb2+. Job plot experiments revealed 1:1 binding stoichiometry for each of the complexes. The association constants for 3a·Ca2+, 3b·Ca2+, 3b·Ba2+, and 3b·Pb2+ were determined by Benesi–Hildebrand plots. On the basis of 1H NMR titration results, Ca2+ was bound to the two partially deprotonated hydroxy azophenol groups and one of the two tetrazole groups of 3a and 3b.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Review of the Finnish BioRefine—New biomass products program
Authors: Mäkinen Tuula , Leppälahti Jukka
Published: August 2009

The BioRefine–New Biomass Products Programme of Tekes, Finnish Funding Agency for Technology and Innovation, for 2007–2012 aims to generate new and unique expertise in the processing of biomass and apply it to the creation of processes, products and services related to biorefineries. A further objective is to promote the development and use of second‐generation production technologies in biofuels for transport. The BioRefine Programme harnesses an extensive network of Finnish research institutes, universities and enterprises. In Finland, the existing know‐how of Finnish forest and energy companies forms the basis for creating new businesses and new products from biomass. Forest industry is expected to be one of the most viable platforms for biorefining in the first stage. Small distributed biorefineries may become important in the next stage. The planned program budget totals EUR 137 million. At mid‐term, the volume of the projects is about EUR 90 million and it is estimated that the total volume of the projects will reach about EUR 200 million. In the program, e.g., technologies for producing biofuels for transport via the synthesis‐gas route and new liquid biofuel concepts based on integrating a fluidized‐bed boiler and fast pyrolysis, are developed and demonstrated. In addition to the production, the use of biofuels is also demonstrated. Greenhouse gas and other environmental impacts are assessed. Activities of the program and the main results achieved in 2007–2009 are presented in the paper. © 2009 American Institute of Chemical Engineers Environ Prog, 2009
Effect of incidence angle with wake passing on a film cooled leading edge: A numerical study
Authors: Montomoli F. , Massini M. , Adami P. , Martelli F.
Published: August 2009

This work presents the numerical study of a film‐cooled blade under the influence of wake passing at different incidence angles. The film cooling technology has been proven to be effective to increase the blade life of first turbine stages. However, the leading edge is affected by an high heat transfer rate and cooling this region is difficult. Moreover, separated regions downstream the coolant injection increases the local heat transfer coefficient and can have a detrimental effect in terms of airfoil life.

This work analyses how the flow field is affected by the wake passing at different incidence angles (−5, 0, 5) and the impact on heat transfer coefficient. The test case is a linear cascade with two rows of cylindrical holes at the leading edge. Two different holes arrangements are compared in terms of film cooling structures, namely AGTB‐B1 and AGTB‐B2 with 0 and 45∘ spanwise inclination. The numerical results show a good agreement with the experiments.

A deeper investigation is carried out on AGTB‐B1. The results obtained show that the wake passing and the incidence angle have a strong effect on coolant jets. In particular, there is a significative impact on coolant redistribution near the leading edge. The wake passing has a stronger effect on pressure side, mainly at negative incidence.

The predictive approach is based on an U‐RANS in‐house CFD solver using a conventional two‐equations closure. In order to avoid extra turbulence production, critical in the leading edge region, the turbulence model incorporates an extra algebraic equation that enforces a realizability constraint. The unsteady formulation is based on a dual time stepping approach with a sliding plane between the moving bars and the cascade. Copyright © 2009 John Wiley & Sons, Ltd.
End of life care for community dwelling older people with dementia: an integrated review
Authors: Goodman Claire , Evans Catherine , Wilcock Jane , Froggatt Katherine , Drennan Vari , Sampson Elizabeth , Blanchard Martin , Bissett Maggie , Iliffe Steve
Published: August 2009

Objective

To review the evidence for end‐of‐life care for community dwelling older people with dementia (including those resident in care homes).

Design

An integrated review synthesised the qualitative and quantitative evidence on end‐of‐life care for community dwelling older people with dementia. English language studies that focused on prognostic indicators for end‐of‐life care, assessment, support/relief, respite and educational interventions for community dwelling older people with dementia were included. A user representative group informed decisions on the breadth of literature used. Each study selected was screened independently by two reviewers using a standardised check list.

Results

Sixty eight papers were included. Only 17% (12) exclusively concerned living and dying with dementia at home. Six studies included direct evidence from people with dementia. The studies grouped into four broad categories: Dementia care towards the end of life, palliative symptom management for people with dementia, predicting the approach of death for people with dementia and decision‐making. The majority of studies were descriptive. The few studies that developed dementia specific tools to guide end of life care and outcome measures specific to improve comfort and communication, demonstrated what could be achieved, and how much more needs to be done.

Conclusions

Research on end‐of‐life care for people with dementia has yet to develop interventions that address the particular challenges that dying with dementia poses. There is a need for investigation of interventions and outcome measures for providing end‐of‐life care in the settings where the majority of this population live and die. Copyright © 2009 John Wiley & Sons, Ltd.
Water losses in the inner delta of the River Niger: water balance and flooded area
Authors: Mahé G. , Bamba F. , Soumaguel A. , Orange D. , Olivry J. C.
Published: August 2009

The inner delta of the River Niger receives runoff from both the River Niger and the River Bani (249 000 km2) and is divided into a northern part (15 000 km2) and a southern part (58 000 km2). The average input and output discharges are approximately 1490 and 900 m3 s−1 (1955/1996), respectively. The annual average water loss is approximately 40% (24‐48%). The losses are greater in the northern (10·5 km3) than in the southern delta (8·2 km3), but this situation was reversed in 1984. The correlation between the output and input discharges is high for the northern part of the delta, but very low for the southern part, where the change in flooded area is likely to be limited. The average flooded area, calculated using a method based on the hydrological balance, is estimated to be about 10 000 km2 (north) and 14 000 km2 (south), which is consistent with the estimates provided by the previous authors. Copyright © 2009 John Wiley & Sons, Ltd.
Colorectal cancer chemoprevention by 2 β‐cyclodextrin inclusion compounds of auraptene and 4′‐geranyloxyferulic acid
Authors: Tanaka Takuji , de Azevedo Mariangela B.M. , Durán Nelson , Alderete Joel B. , Epifano Francesco , Genovese Salvatore , Tanaka Mayu , Tanaka Takahiro , Curini Massimo
Published: August 2009

The inhibitory effects of novel prodrugs, inclusion complexes of 3‐(4′‐geranyloxy‐3′‐methoxyphenyl)‐2‐trans propenoic acid (GOFA) and auraptene (AUR) with β‐cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Male CD‐1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/β‐CD or AUR/β‐CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/β‐CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 ± 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/β‐CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/β‐CD and AUR/β‐CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor‐kappaB, tumor necrosis factor‐α, Stat3, NF‐E2‐related factor 2, interleukin (IL)‐6 and IL‐1β, which were induced in the adenocarcinomas. Our findings indicate that GOFA/β‐CD and AUR/β‐CD, especially GOFA/β‐CD, are therefore able to inhibit colitis‐related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.
Radiation‐induced leukemia among children aged 0–5 years at the time of the Chernobyl accident
Authors: Noshchenko Andriy G. , Bondar Oleksandra Y. , Drozdova Vira D.
Published: August 2009

This case–control study was conducted to estimate the radiation‐induced risk of acute leukemia during the period from 1987 to 1997 among residents 0–5 years of age at the time of the Chernobyl accident in the most radioactively contaminated territories of the Ukraine (Rivno, Zhytomyr, Chernihiv and Cherkasy regions). Data were collected from 246 leukemia cases diagnosed between 1 January, 1987, and 31 December, 1997. Each case was verified and interviewed. Verified cases were compared to 492 randomly selected controls matched by age, sex, type of settlement (rural, semirural and urban) and administrative region of residency. The cumulative level of radiation exposure from the time of the Chernobyl accident to the date of diagnosis was assessed for each case and corresponding controls. Four dose‐range groups were selected for statistical analysis (0–2.9, 3–9.9, 10–99.9 and 100–313.3 mGy). The risk of leukemia was significantly increased (–2.4 [95%CI: 1.4–4.0]) among those with radiation exposure doses higher than 10 mGy (p = 0.01). The association between radiation exposure and risk was stronger among males (–2.8 [95%CI: 1.4–5.5, p = 0.01]), and for cases of acute leukemia that were diagnosed during the period from 1987 to 1992 (–2.5 [95%CI: 1.2–5.1, p = 0.05]), particularly acute myeloid leukemia (–5.8 [95%CI: 1.4–24.6, p = 0.05]). The influence of possible confounders and methods of selecting controls on the leukemia risk assessment was analyzed. The evaluated risk per unit dose is discussed.
Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer
Authors: Zieker Derek , Königsrainer Ingmar , Tritschler Isabel , Löffler Markus , Beckert Stefan , Traub Frank , Nieselt Kay , Bühler Sarah , Weller Michael , Gaedcke Jochen , Taichman Russell S. , Northoff Hinnak , Brücher Björn L.D.M. , Königsrainer Alfred
Published: August 2009

Peritoneal carcinomatosis is a frequent finding in gastric cancer associated with a poor prognosis. The features that enable gastric tumors to disseminate are poorly understood until now. Previously, we showed elevated mRNA levels of phosphoglycerate kinase 1 (PGK1), an adenosine triphosphate‐generating enzyme in the glycolytic pathway, the chemokine receptor 4 (CXCR4), the corresponding chemokine ligand 12 (CXCL12) and β‐catenin in specimens from gastric cancer patients with peritoneal carcinomatosis. In this study, the influence of PGK1 on CXCR4 and β‐catenin was assessed as well as the invasiveness of PGK1 overexpressing cancer cells. In this current study, we found that PGK1 regulates the expression of CXCR4 and β‐catenin at the mRNA and protein levels. On the other hand, CXCR4 regulates the expression of PGK1. Plasmid‐mediated overexpression of PGK1 dramatically increased the invasiveness of gastric cancer cells. Interestingly, inhibition of CXCR4 in cells overexpressing PGK1 produced only a moderate reduction of invasiveness suggesting that, PGK1 itself has a critical role in tumor invasiveness. Immunohistochemistry in specimens from diffuse gastric cancer patients also revealed an overexpression of PGK1 in patients with development of peritoneal carcinomatosis. Therefore, PGK1 may be a crucial enzyme in peritoneal dissemination. Together these findings suggest that the enhanced expression of PGK1 and its signaling targets CXCR4 and β‐catenin in gastric cancer cells promote peritoneal carcinomatosis. Thus, PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum.
The forkhead box M1 transcription factor as a candidate of target for anti‐cancer immunotherapy
Authors: Yokomine Kazunori , Senju Satoru , Nakatsura Tetsuya , Irie Atsushi , Hayashida Yuki , Ikuta Yoshiaki , Harao Michiko , Imai Katsunori , Baba Hideo , Iwase Hirotaka , Nomori Hiroaki , Takahashi Koji , Daigo Yataro , Tsunoda Takuya , Nakamura Yusuke , Sasaki Yutaka , Nishimura Yasuharu
Published: August 2009

The present study attempted to identify a target antigen for immunotherapy for cholangiocarcinoma. Forkhead box M1 (FOXM1) was selected as a candidate antigen based on the data of previous cDNA microarray analysis of clinical samples of cholangiocarcinoma. The level of FOXM1 mRNA was more than 4 times higher in cancer cells in comparison to adjacent normal epithelial cells, in all of 24 samples of cholangiocarcinoma tissues. An immunohistochemical analysis also detected FOXM1 protein in the cancer cells but not in the normal cells. Twenty‐three human FOXM1‐derived peptides predicted to bind to HLA‐A2 were analyzed to determine their ability to induce HLA‐A2‐restricted T cells in HLA‐A2 transgenic mice. FOXM1362‐370 (YLVPIQFPV), FOXM1373‐382 (SLVLQPSVKV), and FOXM1640‐649 (GLMDLSTTPL) peptides primed HLA‐A2‐restricted cytotoxic T lymphocytes (CTLs) in the HLA‐A2 transgenic mice. Human CTL lines reactive to these 3 peptides could also be established from HLA‐A2‐positive healthy donors and cancer patients. Natural processing of the 3 epitopes from FOXM1 protein was confirmed by specific killing of HLA‐A2‐positive FOXM1‐transfectants by peptide‐induced CTLs. FOXM1 is expressed in various types of cancers and it is also functionally involved in oncogenic transformation and the survival of cancer cells. Therefore, FOXM1 may be a suitable target for immunotherapy against various cancers including cholangiocarcinoma.
Changing cancer incidence in Kampala, Uganda, 1991–2006
Authors: Parkin Donald Maxwell , Nambooze Sarah , Wabwire‐Mangen Fred , Wabinga Henry R.
Published: August 2009

Incidence rates of different cancers have been calculated for the population of Kyadondo County (Kampala, Uganda) for a 16‐year period (1991–2006). This period coincides with continuing social and lifestyle changes and the peak and subsequent wane of the epidemic of HIV‐AIDS. There has been an overall increase in the risk of cancer during the period in both sexes, with the incidence rates of cancers of the breast and prostate showing particularly marked increases (4.5% annually). Prostate cancer is now the most common cancer in men. The incidence of cancer of the esophagus, formerly the most common cancer in men and second in frequency in women, has remained relatively constant, whereas the incidence of cancer of the cervix, the most common malignancy in women, continues to increase. Since the early 1990s the incidence of Kaposi sarcoma (KS) in men has declined, and while remaining relatively constant in women, it has been diagnosed at progressively later ages. The rates of pediatric KS have declined by about 1/3rd. The incidence of squamous cell cancers of the conjunctiva has also declined since the mid 1990s. Cancer control in Uganda, as elsewhere in sub‐Saharan Africa, involves meeting the challenge of emerging cancers associated with westernization of lifestyles (large bowel, breast and prostate); although the incidence of cancers associated with poverty and infection (liver, cervix, esophagus) shows little decline, the residual burden of the AIDS‐associated cancers remains a major burden.
Trends in colorectal cancer incidence in Norway 1962–2006: an interpretation of the temporal patterns by anatomic subsite
Authors: Larsen Inger Kristin , Bray Freddie
Published: August 2009

There have been rapid increases in the incidence of colorectal cancer in Norway since the 1960s, and rates rank among the highest worldwide. The primary objectives are to describe trends in left‐ and right‐sided colon cancer and rectal cancer by calendar period and birth cohort and to generate hypotheses as to the etiological factors in operation. Although the age‐adjusted incidence rates of both colon and rectal cancer increased in Norway in both sexes up to the 1980s, subsite‐ and age‐specific analyses reveal a deceleration in the rate of increase thereafter, apparent in the rates of both left‐sided colon and rectal cancer. Overall trends in incidence of right‐sided colon cancer continue to increase in both sexes. Rates in both left‐ and right‐sided colon cancers have tended to stabilize or decrease among successive generations born after 1950, however, while incidence rates of rectal cancer appear to be increasing in recent generations. The all‐ages rates are thus in keeping with the commonly reported “left to right shift” of colon cancer, although standardization masks important observations. The cohort patterns provide further evidence that factors earlier in life are important, and while the complex etiology makes interpretation difficult, modifications in diet, obesity and physical activity in Norway are likely among the drivers of the trends in one or more of the colorectal subsites examined. In summary, the recent downturn in the disease at younger ages provides some reason for optimism, although possible increases in rectal cancer among recent birth cohorts are of concern.
Commentary on Berger, Hohl, and Caspar's (2009) Internet‐based treatment for social phobia: a randomized controlled trial
Authors: Andersson Gerhard , Carlbring Per
Published: August 2009

In this commentary, we discuss the implications of the findings by Berger, Hohl, and Casper (this issue) together with the emerging database on the effects of Internet treatment for social anxiety disorder (social phobia). Their article is the third independent replication of guided Internet treatment of social anxiety disorder, and in this article, we comment on future research challenges and if Internet treatment now can be regarded as ready for dissemination into regular clinical settings. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1–3, 2009.
Sensing invasion: Cell surface receptors driving spreading of glioblastoma
Authors: Teodorczyk Marcin , Martin‐Villalba Ana
Published: August 2009

Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. One main source of its high malignancy is the invasion of isolated tumour cells into the surrounding parenchyma, which makes surgical resection an insufficient therapy in nearly all cases. The invasion is triggered by several cell surface receptors including receptor tyrosine kinases (RTKs), G protein‐coupled receptors (GPCRs), TGF‐β receptor, integrins, immunoglobulins, tumour necrosis factor (TNF) family, cytokine receptors, and protein tyrosine phosphatase receptors. The cross‐talk between cell‐surface receptors and the redundancy of downstream effectors make analysis of invasive signals even more complex. Therapies involving inhibition of single receptors do not give promising outcomes and a thorough knowledge of invasive signals of common and exclusive signalling components is required for design of best combinatory treatment schemes to fight the disease. J. Cell. Physiol. 222:1–10, 2010. © 2009 Wiley‐Liss, Inc.
A chimeric adenovirus with an Ad 3 fiber knob modification augments glioma virotherapy
Authors: Nandi Suvobroto , Ulasov Ilya V. , Rolle Cleo E. , Han Yu , Lesniak Maciej S.
Published: August 2009

Background

Malignant gliomas remain refractory to treatment despite advances in chemotherapy and surgical techniques. Viral vectors developed to treat gliomas have had low transduction capabilities, limiting their use. Gliomas over‐express CD46, CD80, and CD86, all of which bind adenovirus serotype 3.

Methods

To increase the infectivity and replication of oncolytic vectors in malignant brain tumors, we created a conditionally replicating adenovirus, CRAd‐Survivin‐5/3, which contains a survivin promoter‐driving E1A and a chimeric fiber consisting of adenovirus serotype 3 knob.

Results

In vitro, this modified CRAd showed ten‐ to 100‐fold increased cytotoxicity against glioma cells. Ex vivo analysis of primary glioblastoma multiforme samples infected with CRAd‐Survivin‐5/3 showed an increase in cytotoxicity of 20–30% compared to adenovirus wild‐type (AdWT). In normal human astrocytes and normal brain tissues, CRAd‐Survivin‐5/3 exhibited 30–40% and 10–15% lower cytotoxicity than AdWT, respectively. In an intracranial xenograft model of glioma, this oncolytic virus increased tumor‐free survival and overall lifespan by 50% compared to controls (p < 0.05).

Conclusions

CRAd‐Survivin‐5/3 represents an attractive alternative to existing vectors and should be tested further in the pre‐clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.
FK506 as an adjuvant of tolerogenic DNA vaccination for the prevention of experimental autoimmune encephalomyelitis
Authors: Kang Youmin , Zhao Jia , Liu Yue , Chen Aoshuang , Zheng Guoxing , Yu Yang , Mi Jianjie , Zou Qiang , Wang Bin
Published: August 2009

Background

DNA vaccination is a strategy that has been developed primarily to elicit protective immunity against infection and cancer.

Methods

DNA vaccine was used, in conjunction with an immunosuppressant, to tolerize harmful autoimmunity.

Results

Immunization of C57BL/6 mice with MOG35–55, a myelin oligodendrocyte glycoprotein‐derived peptide, and FK506 (Tacrolimus) as a tolerogenic adjuvant stimulated regulatory dendritic cells, induced antigen‐specific regulatory T cells (Treg), and protected the animals from subsequent induction of experimental autoimmune encephalomyelitis (EAE). After EAE induction, there were fewer lymphocytes, including fewer T helper 17 cells, and more Treg infiltrating the spinal cord in the immunized mice compared to in control mice. Furthermore, at the peak of the EAE manifestation, CD4 T cells in the immunized mice showed decreased expression of interferon‐γ and interleukin (IL)‐17, but not IL‐4, in treated mice.

Conclusions

DNA vaccination, when applied with an immunosuppressant as adjuvant, can induce antigen‐specific tolerance and prevent autoimmune disease. Copyright © 2009 John Wiley & Sons, Ltd.