bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps
Authors: Valla Vasiliki
Published: May 2010

Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas.Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed.Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.
Periodic Solutions for a Numerical Discretization Neural Network
Authors: Lu Chun
Published: May 2010

The existence and global exponential stability of periodic solutions for a class of numerical discretization neural networks are considered. Using coincidence degree theory and Lyapunov method, sufficient conditions for the existence and global exponential stability of periodic solutions are obtained. Numerical simulations are given to illustrate the results.
Effect ofAgaricus blazeiMurill on the Pulmonary Tissue of Animals with Streptozotocin-Induced Diabetes
Authors: Di Naso Fábio Cangeri , de Mello Rodrigo Noronha , Bona Sílvia , Dias Alexandre Simões , Porawski Marilene , Ferraz Alexandre de Barros Falcão , Richter Marc François , Marroni Norma Possa
Published: May 2010

The present study was designed to evaluate the oxidative stress as well as the therapeutic effect ofAgaricus blazeiMuril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.).Agaricus blazeiMuril was administered daily starting 40 days after disease onset.A. Blazeiwas tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening ofA. Blazeidetected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43±0.09;P<.001) as compared to the control group (0.18±0.02), followed by a reduction in theA. Blazei-treated group (0.33±0.04;P<.05). iNOS was found increased in the lung in diabetic rats and reduced in theA. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. TheA. Blazeitreatment effectively reduced the oxidative stress and contributed to tissue recovery.
Plasma Fibronectin Promotes Lung Metastasis by Contributions to Fibrin Clots and Tumor Cell Invasion
Authors: Malik Gunjan , Knowles Lynn M. , Dhir Rajiv , Xu Shuping , Yang Shuting , Ruoslahti Erkki , Pilch Jan
Published: May 2010

The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating plasma fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin αvβ3. In vitro studies showed that fibrin-fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-fibronectin complexes to induce the activation of integrin αvβ3. Our findings reveal an important contribution of plasma fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a fibronectin-αvβ3 integrin axis, in which plasma fibronectin has to be incorporated into the blood clot. Cancer Res; 70(11); 4327–34. ©2010 AACR.
Strain-Specific Susceptibility for Pulmonary Metastasis of Sarcoma 180 Cells in Inbred Mice
Authors: Vikis Haris G. , Jackson Erin N. , Krupnick Alexander S. , Franklin Andrew , Gelman Andrew E. , Chen Qiong , Piwnica-Worms David , You Ming
Published: May 2010

Most cancer deaths are a result of metastasis. To extend our understanding of the factors that influence the process, we aimed to develop a mouse model of pulmonary metastasis that can be assayed in multiple inbred mouse strains for further use in identification of host genetic variants that influence metastasis. We used i.v. injection of Sarcoma 180 (S180) cells, which can be tracked and quantified by bioluminescence imaging. We observed growth of S180 cells solely in the lung and observed a wide range of pulmonary metastasis among inbred mouse strains. Interestingly, we noted that the BTBRT+tf/J strain exhibited complete clearance and provide evidence that the mechanism of resistance may involve immune factors, as strains subjected to whole-body irradiation are significantly more susceptible to tumor growth. One possible mechanism of resistance to pulmonary metastasis in BTBRT+tf/J mice may require T-cell function. Our experiments present a new mouse model for further characterization of the genetics and mechanisms of pulmonary metastasis. Cancer Res; 70(12); 4859–67. ©2010 AACR.
Genome-Wide Mapping of Estrogen Receptor-β–Binding Regions Reveals Extensive Cross-Talk with Transcription Factor Activator Protein-1
Authors: Zhao Chunyan , Gao Hui , Liu Yawen , Papoutsi Zoi , Jaffrey Sadaf , Gustafsson Jan-Åke , Dahlman-Wright Karin
Published: May 2010

Estrogen signaling can occur through a nonclassical pathway involving the interaction of estrogen receptors (ER) with other transcription factors such as activator protein-1 (AP-1) and SP-1. However, there is little mechanistic understanding about this pathway, with conflicting results from in vitro investigations. In this study, we applied the ChIP-on-chip approach to identify ERβ-binding sites on a genome-wide scale, identifying 1,457 high-confidence binding sites in ERβ-overexpressing MCF7 breast cancer cells. Genes containing ERβ-binding sites can be regulated by E2. Notably, ∼60% of the genomic regions bound by ERβ contained AP-1–like binding regions and estrogen response element–like sites, suggesting a functional association between AP-1 and ERβ signaling. Chromatin immunoprecipitation (ChIP) analysis confirmed the association of AP-1, which is composed of the oncogenic transcription factors c-Fos and c-Jun, to ERβ-bound DNA regions. Using a re-ChIP assay, we showed co-occupancy of ERβ and AP-1 on chromatin. Short interfering RNA–mediated knockdown of c-Fos or c-Jun expression decreased ERβ recruitment to chromatin, consistent with the role of AP-1 in mediating estrogen signaling in breast cancer cells. Additionally, ERα and ERβ recruitment to AP-1/ERβ target regions exhibited gene-dependent differences in response to antiestrogens. Together, our results broaden insights into ERβ DNA-binding at the genomic level by revealing crosstalk with the AP-1 transcription factor. Cancer Res; 70(12); 5174–83. ©2010 AACR.
CUB Domain–Containing Protein 1, a Prognostic Factor for Human Pancreatic Cancers, Promotes Cell Migration and Extracellular Matrix Degradation
Authors: Miyazawa Yuri , Uekita Takamasa , Hiraoka Nobuyoshi , Fujii Satoko , Kosuge Tomoo , Kanai Yae , Nojima Yoshihisa , Sakai Ryuichi
Published: May 2010

CUB domain–containing protein 1 (CDCP1) is a membrane protein that is highly expressed in several solid cancers. We reported previously that CDCP1 regulates anoikis resistance as well as cancer cell migration and invasion, although the underlying mechanisms have not been elucidated. In this study, we found that expression of CDCP1 in pancreatic cancer tissue was significantly correlated with overall survival and that CDCP1 expression in pancreatic cancer cell lines was relatively high among solid tumor cell lines. Reduction of CDCP1 expression in these cells suppressed extracellular matrix (ECM) degradation by inhibiting matrix metalloproteinase-9 secretion. Using the Y734F mutant of CDCP1, which lacks the tyrosine phosphorylation site, we showed that CDCP1 regulates cell migration, invasion, and ECM degradation in a tyrosine phosphorylation–dependent manner and that these CDCP1-associated characteristics were inhibited by blocking the association of CDCP1 and protein kinase Cδ (PKCδ). CDCP1 modulates the enzymatic activity of PKCδ through the tyrosine phosphorylation of PKCδ by recruiting PKCδ to Src family kinases. Cortactin, which was detected as a CDCP1-dependent binding partner of PKCδ, played a significant role in migration and invasion but not in ECM degradation of pancreatic cells. These results suggest that CDCP1 expression might play a crucial role in poor outcome of pancreatic cancer through promotion of invasion and metastasis and that molecules blocking the expression, phosphorylation, or the PKCδ-binding site of CDCP1 are potential therapeutic candidates. Cancer Res; 70(12); 5136–46. ©2010 AACR.
Notch Signaling Determines the M1 versus M2 Polarization of Macrophages in Antitumor Immune Responses
Authors: Wang Yao-Chun , He Fei , Feng Fan , Liu Xiao-Wei , Dong Guang-Ying , Qin Hong-Yan , Hu Xing-Bin , Zheng Min-Hua , Liang Liang , Feng Lei , Liang Ying-Min , Han Hua
Published: May 2010

Macrophages are important tumor-infiltrating cells and play pivotal roles in tumor growth and metastasis. Macrophages participate in immune responses to tumors in a polarized manner: classic M1 macrophages produce interleukin (IL) 12 to promote tumoricidal responses, whereas M2 macrophages produce IL10 and help tumor progression. The mechanisms governing macrophage polarization are unclear. Here, we show that the M2-like tumor-associated macrophages (TAM) have a lower level of Notch pathway activation in mouse tumor models. Forced activation of Notch signaling increased M1 macrophages which produce IL12, no matter whether M1 or M2 inducers were applied. When Notch signaling was blocked, the M1 inducers induced M2 response in the expense of M1. Macrophages deficient in canonical Notch signaling showed TAM phenotypes. Forced activation of Notch signaling in macrophages enhanced their antitumor capacity. We further show that RBP-J–mediated Notch signaling regulates the M1 versus M2 polarization through SOCS3. Therefore, Notch signaling plays critical roles in the determination of M1 versus M2 polarization of macrophages, and compromised Notch pathway activation will lead to the M2-like TAMs. These results provide new insights into the molecular mechanisms of macrophage polarization and shed light on new therapies for cancers through the modulation of macrophage polarization through the Notch signaling. Cancer Res; 70(12); 4840–9. ©2010 AACR.
Prostate Stem Cell Antigen: A Jekyll and Hyde Molecule?
Authors: Saeki Norihisa , Gu Jian , Yoshida Teruhiko , Wu Xifeng
Published: May 2010

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Although PSCA is thought to be involved in intracellular signaling, much remains unknown about its physiological function and regulatory mechanism in normal and cancer cells. It is up-regulated in several major cancers including prostate, bladder, and pancreatic cancers. The expression of PSCA is positively correlated with advanced clinical stage and metastasis in prostate cancers and is also associated with malignant progression of premalignant prostate lesions. Therefore, PSCA has been proposed as a biomarker of diagnosis and prognosis, as well as a target of therapy for these cancers. In addition, PSCA has also shown clinical potential in immunotherapy as a prostate-specific antigen, which, when presented by dendritic cells, may elicit strong tumor-specific immunity. In contrast, PSCA is down-regulated in esophageal and gastric cancer and may have a tumor-suppressing function in the gastric epithelium. Recent exciting findings that genetic variations of PSCA conferred increased risks of gastric cancer and bladder cancer have opened up a new avenue of research about the pathological function of PSCA. PSCA seems to be a Jekyll and Hyde molecule that plays differential roles, tumor promoting or suppressing, depending on the cellular context. Clin Cancer Res; 16(14); 3533–8. ©2010 AACR.
Pralatrexate Is Synergistic with the Proteasome Inhibitor Bortezomib inIn vitroandIn vivoModels of T-Cell Lymphoid Malignancies
Authors: Marchi Enrica , Paoluzzi Luca , Scotto Luigi , Seshan Venkatraman E. , Zain Jasmine M. , Zinzani Pier Luigi , O'Connor Owen A.
Published: May 2010

Purpose: Pralatrexate (10-propargyl-10-deazaaminopterin) is an antifolate with improved cellular uptake and retention due to greater affinity for the reduced folate carrier (RFC-1) and folyl-polyglutamyl synthase. Based on the PROPEL data, pralatrexate was the first drug approved for patients with relapsed and refractory peripheral T-cell lymphoma. Bortezomib is a proteasome inhibitor that has shown some activity in patients with T-cell lymphoma.

Experimental Design: Assays for cytotoxicity including mathematical analysis for synergism, flow cytometry, immunoblotting, and a xenograft severe combined immunodeficient-beige mouse model were used to explore the in vitro and in vivo activities of pralatrexate alone and in combination with bortezomib in T-cell lymphoid malignancies.

Results: In vitro, pralatrexate and bortezomib exhibited concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. Pralatrexate showed synergism when combined with bortezomib in all cell lines studied. Pralatrexate also induced potent apoptosis and caspase activation when combined with bortezomib across the panel. Cytotoxicity studies on normal peripheral blood mononuclear cells showed that the combination was not more toxic than the single agents. Western blot assays for proteins involved in broad growth and survival pathways showed that p27, NOXA, HH3, and RFC-1 were all significantly modulated by the combination. In a severe combined immunodeficient-beige mouse model of transformed cutaneous T-cell lymphoma, the addition of pralatrexate to bortezomib enhanced efficacy compared with either drug alone.

Conclusion: Collectively, these data suggest that pralatrexate in combination with bortezomib represents a novel and potentially important platform for the treatment of T-cell malignancies. Clin Cancer Res; 16(14); 3648–58. ©2010 AACR.
Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis
Authors: Rajasekaran Sigrid A. , Huynh Thu P. , Wolle Daniel G. , Espineda Cromwell E. , Inge Landon J. , Skay Anna , Lassman Charles , Nicholas Susanne B. , Harper Jeffrey F. , Reeves Anna E. , Ahmed Mansoor M. , Leatherman James M. , Mullin James M. , Rajasekaran Ayyappan K.
Published: May 2010

Epithelial-to-mesenchymal transition (EMT) is an important developmental process, participates in tissue repair, and occurs during pathologic processes of tumor invasiveness, metastasis, and tissue fibrosis. The molecular mechanisms leading to EMT are poorly understood. Although it is well documented that transforming growth factor (TGF)-β plays a central role in the induction of EMT, the targets of TGF-β signaling are poorly defined. We have shown earlier that Na,K-ATPase β1-subunit levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients' tumor samples. In this study, we provide evidence that Na,K-ATPase is a new target of TGF-β1–mediated EMT in renal epithelial cells, a model system used in studies of both cancer progression and fibrosis. We show that following treatment with TGF-β1, the surface expression of the β1-subunit of Na,K-ATPase is reduced, before well-characterized EMT markers, and is associated with the acquisition of a mesenchymal phenotype. RNAi-mediated knockdown confirmed the specific involvement of the Na,K-ATPase β1-subunit in the loss of the epithelial phenotype and exogenous overexpression of the Na,K-ATPase β1-subunit attenuated TGF-β1–mediated EMT. We further show that both Na,K-ATPase α- and β-subunit levels are highly reduced in renal fibrotic tissues. These findings reveal for the first time that Na,K-ATPase is a target of TGF-β1–mediated EMT and is associated with the progression of EMT in cancer and fibrosis. Mol Cancer Ther; 9(6); 1515–24. ©2010 AACR.
Endocytosis of PEGylated Agents Enhances Cancer Imaging and Anticancer Efficacy
Authors: Chuang Kuo-Hsiang , Wang Hsin-Ell , Chen Fang-Ming , Tzou Shey-Cherng , Cheng Chiu-Min , Chang Ya-Chen , Tseng Wei-Lung , Shiea Jentaie , Lin Shiu-Ru , Wang Jaw-Yuan , Chen Bing-Mae , Roffler Steve R. , Cheng Tian-Lu
Published: May 2010

PEGylated nanoparticles and macromolecules are increasingly used in cancer imaging and anticancer treatment. The role of receptor-mediated endocytosis in the efficacy of these agents, however, has not been clearly defined. Here, we developed a matched pair of endocytic and nonendocytic receptors to directly and unambiguously assess this issue. The ligand-binding domains of the low-density lipoprotein receptor (LDLR) or a truncated LDLR lacking the NPXY endocytosis motif (ΔLDLR) were replaced with an anti–polyethylene glycol antibody (αPEG) to form endocytic αPEG-LDLR and nonendocytic αPEG-ΔLDLR receptors. The receptors were stably expressed at similar levels on the surface of HCC36 cells. HCC36/αPEG-LDLR cells, but not HCC36/αPEG-ΔLDLR cells, rapidly endocytosed PEG-quantum dots and PEG-liposomal doxorubicin (Lipo-Dox) in vitro and in vivo. Lipo-Dox was significantly more cytotoxic to HCC36/αPEG-LDLR cells than to HCC36/αPEG-ΔLDLR cells. HCC36/αPEG-LDLR tumors also accumulated significantly more PEGylated near-IR probes (PEG-NIR797) and PEG-liposomal-111In than HCC36/αPEG-ΔLDLR tumors in vivo. Furthermore, Lipo-Dox more significantly suppressed the growth of established HCC36/αPEG-LDLR tumors as compared with HCC36/αPEG-ΔLDLR tumors. Our data show that endocytosis of PEGylated probes and drugs enhances both cancer imaging and anticancer efficacy, indicating that endocytic receptors are superior targets for the design of cancer imaging probes and immunoliposomal drugs. Mol Cancer Ther; 9(6); 1903–12. ©2010 AACR.
Mortality in the Randomized, Controlled Lung Intergroup Trial of Isotretinoin
Authors: Lee J. Jack , Feng Lei , Reshef Daniel S. , Sabichi Anita L. , Williams Brendell , Rinsurongkawong Waree , Wistuba Ignacio I. , Lotan Reuben , Lippman Scott M.
Published: May 2010

In 2001, we reported that mortality may have been higher with isotretinoin (30 mg/d for 3 years) than with placebo in the subgroup of current smokers among the 1,166 patients with definitively resected early-stage non–small cell lung cancer who participated in the randomized, controlled Lung Intergroup Trial. We report the overall and cause (cancer, cardiovascular disease, or other)-specific mortality associated with long-term isotretinoin after an extended median follow-up of 6.2 years that included the capture of cause-of-death data from 428 deceased patients. Overall mortality was 36.7% in each of the two trial arms, about two thirds related to cancer and one third to other or unknown causes. Overall and cancer deaths increased in current smokers in the isotretinoin arm during the treatment and the extended follow-up period. No mortality end point increased among never smokers and former smokers taking isotretinoin, and cancer deaths decreased marginally in this combined subgroup. Isotretinoin also increased deaths from cardiovascular disease in current smokers. The present analysis supports the safety of protracted isotretinoin use in the combined group of never smokers and former smokers, which has important public health implications, for example, for treating acne in young people. The increased mortality in current smokers in this study is further evidence of the multifaceted danger of active smoking. The overall indications of this study have public health implications for treating acne in young people and other uses of retinoids in smokers. Cancer Prev Res; 3(6); 738–44. ©2010 AACR.
Slowing of Alternating Forearm Movements Is Associated with Cognitive Impairment in Community-Dwelling Older People
Authors: Bramell-Risberg E. , Jarnlo G.-B. , Elmståhl S.
Published: May 2010

Background/Aims: Motor impairment is an important aspect of cognitive decline in older adults. It has been suggested that complex motor control is affected earlier than gross motor control. The aims were to investigate if complex hand motor function was more affected than gross motor function in cognitively impaired older subjects, and to present reference values. Methods: Alternating forearm movements and grip strength were studied in 301 cases, 419 intermediates and 1,207 controls, aged 60–93 years, controlling for demographic, health-related and functional factors and comorbidity. Global cognitive function was assessed by the Mini-Mental State Examination, and episodic memory by 3-word delayed recall. Grip strength was assessed by the Grippit®. The frequency of alternating movements during 10 s was registered electronically. Results: Alternating movements but not grip strength was associated with cognitive impairment (right: p = 0.006; left: p = 0.022). The mean alternating movements for the 70-year-old male cases compared to the controls were 2.3 versus 2.5 Hz for the right, and 2.2 versus 2.4 Hz for the left arm (p < 0.05), and for the 60-year-old women 2.0 versus 2.3 Hz for the right arm (p < 0.05). Conclusion: Complex but not gross hand motor function is associated with early cognitive impairment.
Modulation of Gene Activity in Androgen-Induced Sex Reversal in the Garden Lizard, Calotes versicolor
Authors: Chakraborty A. , Raman R.
Published: May 2010

The Indian garden lizard, Calotes versicolor, an apparently non-chromosomal sex determination (CSD), non-temperature-dependent sex determination (TSD) species, represents a unique category of reptiles where male hormone-treated embryos emerge as males. The present paper traces the modulation of gene activity in the embryonic gonad following dihydrotestosterone (DHT) administration on day 8 of embryonic development. Expression of CvAR, CvWnt4, CvDmrt1 and CvSox9 genes has been studied in the mesonephros gonadal complex (MGC) 2 and 6 days after the treatment by RT-PCR and real-time qPCR. In the treated (30 µg/egg) embryos (sacrificed 48 h after treatment), CvAR was expressed in almost all the MGCs in contrast to its dimorphic expression in controls. CvWnt4, the autosomal ovary-specific gene, which has only basal level of expression in controls, was further down-regulated in the treated embryos. The dimorphic expression pattern of the male-specific CvSox9 and CvDmrt1 does not deviate from that seen in controls, suggesting that it acts upstream of CvAR. It appears that in C. versicolor, the primary sex determining switch for testis is essentially genetic (CvSox9 and CvDmrt1), but the genetic pathway of ovary differentiation, which is initiated later in development, is flexible enough to be modulated by hormones, as in other TSD and genetic sex determination (GSD) reptiles. One of the mechanisms of this flexibility, it appears, could be silencing of the ovary-inducing genes by the male hormones.
No Differences in the Sry Gene between Males and XY Females in Akodon (Rodentia, Cricetidae)
Authors: Sánchez A. , Marchal J.A. , Romero-Fernández I. , Pinna-Senn E. , Ortiz M.I. , Bella J.L. , Lisanti J.A.
Published: May 2010

Several species of the South American genus Akodon present fully fertile XY females besides XX ones. To analyze the possibility of a Sry mutation as the cause of sex reversal in A. azarae and A. boliviensis, we determined the sequence of the Sry gene in 2 males and 3 XY females from each of these species. The Sry gene sequence was also studied in A. dolores, a species that does not have XY females. In inter-specific comparisons, the percentage identities with respect to the region analyzed varied between 96.8% and 97.9%. An ORF of 543 nucleotides was identified, and the predicted Sry proteins comprised 180 amino acids, with an HMG domain of 83 amino acids. Our results indicate that female sex reversal in A. azarae and A. boliviensis cannot be explained by sequence differences in the Sry region analyzed here, which includes the complete ORF and, together with previous results concerning the inheritance of the XY condition, show that Sry mutation is not the basis of sex reversal.
Validation of the German Revised Addenbrooke’s Cognitive Examination for Detecting Mild Cognitive Impairment, Mild Dementia in Alzheimer’s Disease and Frontotemporal Lobar Degeneration
Authors: Alexopoulos P. , Ebert A. , Richter-Schmidinger T. , Schöll E. , Natale B. , Aguilar C.A. , Gourzis P. , Weih M. , Perneczky R. , Diehl-Schmid J. , Kneib T. , Förstl H. , Kurz A. , Danek A. , Kornhuber J.
Published: May 2010

Background/Aims: The diagnostic accuracy of the German version of the revised Addenbrooke’s Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer’s disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. Methods: The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. Results: The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD [area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. Conclusion: The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia.
The Role of Tubulointerstitial Inflammation in the Progression of Chronic Renal Failure
Authors: Rodríguez-Iturbe Bernardo , García García Guillermo
Published: May 2010

There is compelling evidence that interstitial inflammation plays a central role in the loss of renal function in chronic renal disease. The combined effects of interstitial inflammation, oxidative stress and local angiotensin II activity result in the disruption of glomerulus-tubule continuity, the development of pathogenic hypoxia, the generation of myofibroblasts and fibrosis, and the impairment of the protective autoregulation of glomerular blood flow that leads to glomerulosclerosis. The association between proteinuria and progression of chronic kidney disease is firmly established. Proximal tubular cells (PTC) exposed to high concentration of proteins produce proinflammatory and profibrotic factors. The activation of nuclear factor ĸB and the signal transducer and activator of transcription results in the upregulation of a variety of cytokines and chemokines, overexpression of adhesion molecules and interstitial infiltration of inflammatory cells. Fibrosis is promoted by release of transforming growth factor β, which induces myofibroblast formation and collagen deposition. Finally, the participation of vitamin D3 deficiency in the development of tubulointerstitial fibrosis is reviewed. The molecule 1,25-(OH)2D3 modulates PTC proliferation, suppresses fibroblast activation and matrix production, reduces epithelial mesenchymal transition and downregulates the genes of the renin-angiotensin system, which are critical steps in the development of a scarred kidney.
Advanced Coronary Artery Calcification Is Associated with Ischemic Stroke
Authors: Kim Beom Joon , Choi Su-Yeon , Lee Seung-Hoon , Kim Chi Kyung , Ryu Wi-Sun , Han Moon-Ku , Oh Byung-Hee , Bae Hee-Joon , Yoon Byung-Woo
Published: May 2010

Background: Coronary artery calcification (CAC) is widely accepted as a quantitative index of subclinical atherosclerosis in the coronary artery, and is utilized as a valuable tool for the global risk assessment of cardiovascular events in individuals at intermediate risk. However, the association between CAC and ischemic stroke has not been evaluated. Methods: CAC scores were measured in 401 consecutive first-ever acute ischemic stroke patients and in 5,420 healthy subjects who underwent detailed medical health screening. The authors randomly matched case:referent sets (1:2) for gender, age, hypertension, diabetes and hyperlipidemia. Accordingly, 290 stroke cases were matched with 580 referent controls. Results: Moderate-to-extensive CAC (CAC ≧100) was detected in 78 (26.9%) of the ischemic stroke cases and in 120 (20.7%) of the referent controls. Conditional logistic regression analysis, which was conducted to investigate the association between categorized CAC scores and ischemic stroke, and adjusted for other relevant confounders, revealed that moderate-to-extensive CAC was associated with the occurrence of ischemic stroke (OR 1.72, 95% CI 1.05–2.80, compared to the subjects with no CAC). The mean ± SE of the AUC-ROC curve for Framingham risk score (FRS) plus CAC score (0.760 ± 0.018) was significantly greater than that of FRS alone (0.748 ± 0.018; p = 0.005). Conclusions: Our results demonstrate that moderate-to-extensive CAC is associated with an increased occurrence of ischemic stroke. In view of the contribution made by CAC to the risk assessment of cardiovascular diseases, the CAC score may be utilized to evaluate the risk of ischemic stroke.
Trends in Baseline Patient Characteristics during the Years 1995–2008: Observations from Riks-Stroke, the Swedish Stroke Register
Authors: Appelros Peter , Jonsson Fredrik , Asplund Kjell , Eriksson Marie , Glader Eva-Lotta , Hulter Åsberg Kerstin , Norrving Bo , Stegmayr Birgitta , Terént Andreas ,   for the Riks-Stroke Collaboration
Published: May 2010

Background: Reported improvements in outcome in stroke patients treated in hospital are often attributed to advances in stroke care. However, secular trends in patient characteristics that are present already on admission to hospital may also contribute to improved outcome. Methods: Time trends for baseline data (289,854 stroke admittances) in Riks-Stroke, the Swedish national quality register for stroke care, were analyzed for the years 1995 through 2008. The following data were included: number of strokes for each year, age, sex, risk factors, stroke subtype, stroke severity, functional status and need of external home service before the stroke. Results: The number of annually reported strokes increased until 2005. The proportion of recurrent strokes decreased from 28.0 to 25.9%. The mean age at first-ever stroke increased in women, but not in men. The proportion of smokers dropped, and the proportion of patients who had treated hypertension increased. The stroke severity decreased in men. The prestroke functional status (walking, dressing, toileting) improved in both sexes over these years. More patients lived alone in 2008 than in 1995, and more had home help service. Conclusions: Many baseline parameters in Riks-Stroke have changed over the years. This has consequences for the interpretation of outcome data. Some changes may be due to inclusion bias, others due to alterations in general health, evolution of vascular risk factors or demographics.
Cognitive-Behavioral Therapy for Threshold and Subthreshold Anorexia Nervosa: A Three-Year Follow-Up Study
Authors: Ricca Valdo , Castellini Giovanni , Lo Sauro Carolina , Mannucci Edoardo , Ravaldi Claudia , Rotella Francesco , Faravelli Carlo
Published: May 2010

Background: Few long-term follow-up studies have evaluated the response to psychotherapeutical interventions in anorexia nervosa (AN). The effectiveness of individual cognitive-behavioral therapy (CBT) and the possible predictors of outcome in outpatients suffering from threshold and subthreshold AN (s-AN) were evaluated. Methods: At the beginning (T0) and at the end of treatment (T1), and 3 years after the end of treatment (T2), 53 subjects with AN and 50 with s-AN (all DSM-IV criteria except amenorrhea or underweight) were assessed by a face-to-face clinical interview and by self-reported questionnaires for eating attitudes and behavior (Eating Disorder Examination Questionnaire), body uneasiness (Body Uneasiness Test) and general psychopathology (Symptom Checklist, Beck Depression Inventory, State-Trait Anxiety Inventory). Results: No deaths occurred during the treatment and the follow-up period. At the end of the follow-up 34 subjects (33%) initially enrolled in the study obtained a full recovery. AN and s-AN patients did not show significant differences on most of the clinical measures at baseline and in terms of treatment response (T1, T2). The reduction in weight and shape concerns was associated with weight gain at T1 and T2, and the shape concern level at baseline represented the main risk factor for recovery and treatment resistance. According to survival analysis, patients with high shape concern had a lower probability of remission across time. Conclusions: The distinction between threshold and subthreshold AN does not seem to be of clinical relevance in terms of response to CBT. Shape concern rather than demographic or general psychopathological features represents the best predictor of outcome for CBT.
Neutrophil Gelatinase-Associated Lipocalin and Hepcidin: What Do They Have in Common and Is There a Potential Interaction?
Authors: Malyszko Jolanta , Tesař Vladimir , Macdougall Iain C.
Published: May 2010

Iron is the fourth most common element in the Earth’s crust and is crucial for life. Over the last few years, our understanding of iron metabolism has dramatically increased due to the discovery of hepcidin, which is produced by hepatocytes and modulated in response to anemia, hypoxia and inflammation. It has been found that anemia upregulates lipocalin 2 (NGAL; neutrophil gelatinase-associated lipocalin) in the liver and serum. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin and NGAL in iron metabolism and its regulation, particularly in kidney disease. Elevated NGAL a few days after insult is a possible preventive or protective mechanism limiting renal injury. NGAL is an innate antibacterial factor as well as hepcidin. NGAL binds siderophores, thereby preventing iron uptake by bacteria. Hepcidin, an antibacterial defensin, prevents iron absorption from the gut and iron release from macrophages, leading to hypoferremia and anemia. Both proteins sequester iron, but by different mechanisms. However, these proteins involved in iron metabolism do not seem to be independently related. Taking into account the antimicrobial moieties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure.
The Study and Treatment, on a Neurological Ward, of Abnormally Aggressive Patients with Focal Brain Disease (Part 2 of 2)
Authors: Blumer Dietrich P. , Williams Harold W. , Mark Vernon H.
Published: May 2010

Thirty-six patients with a history of aggressive violent behavior and/or limbic brain disease were studied on an open neurological-neurosurgical ward by psychiatrists, neurologists and neurosurgeons, complemented by a staff of nurses and aides especially chosen and trained by physicians. Patient history, demographic, physical, neurological, electrophysiologic, psychiatric and roentgenographic findings are presented, as well as the problems and shortcomings of studying such a group within a general hospital framework. The need for close cooperation between psychiatrists and neurologists in dealing with the violent prone, brain diseased patient is emphasized.
Stereotactic Treatment of Action Myoclonus in a Case of Combined Status marmoratus and Multiple Sclerosis (Part 2 of 2)
Authors: Hassler R. , Schmidt K. , Riechert T. , Mundinger F.
Published: May 2010

A patient, who suffered from nonprogressive athetotic-myoclonic hyperkinesia of the left arm and spastic paresis of the underdeveloped left leg since early childhood, experienced a febrile episode at the age of 23, after which a weakness and ataxia of the right limbs with frequent falling persisted; at the age of 28, he developed a right-sided rigidity, tremor at rest and mask-like face as sequelae of encephalitis disseminata exacerbations. The violent intention myoclonus of the left side of the body could be abolished by stereotactic coagulation in the V.o.p and V.o.a and zona incerta until death 11 days later. The athetotic myoclonic hyperkinesia is the consequence of a left-sided severe status marmoratus of the right putamen with extensive loss of nerve cells and shrinkage. The additional nerve cell loss in the right substantia nigra due to demyelinating encephalitic foci did not produce Parkinson symptoms, because these require a normal striatum. This loss did, however, exaggerate the original hyperkinesia to a violent intention myoclonus, which was abolished by interruption of dentatothalamic afferents to the V.o.p nucleus and of pallidothalamic afferents to the V.o.a nucleus. The Parkinson syndrome of the right side is due to demyelinating foci of different ages. The Parkinson symptoms were manifest on the right side, because the left status marmoratus did not severely reduce the striatal nerve cells. In this case, there is no indication that the introduction of the stereotactic electrode has precipitated new demyelinating foci.
Introduction: State Development and International Migration
Authors: Ueda Reed
Published: May 2010

Recent and current research has increasingly approached immigration and ethnic factors from the perspective of historical state development, taking into account regional and global dimensions. The articles in this special issue reflect the innovative conceptual frameworks and empirical methodology utilized in this approach. They indicate how the field of immigration studies is integrating political and historical analysis.
Strengthening International Studies in India
Authors: Alagappa Muthiah
Published: May 2010

This report takes stock of the state of the field of international studies in India and recommends a vision and measures to strengthen the field and make it equal to those in leading institutions and programmes around the world. The ultimate goals of the measures recommended in the report are to:

a. make India a leading centre of knowledge and education in international studies;

b. produce a substantive pool of Indian scholars doing cutting-edge work that contributes to the production and accumulation of knowledge;

c. produce first-rate graduates to meet the demands and opportunities arising from the modernization and rise of India in a changing world; and

d. ensure that Indian IS scholarship contributes to increasing the knowledge base on India’s international role as a responsible power fostering peace, security, good governance, economic development and resolution of a wide range of problems in its immediate region and the world.

The vision, measures and strategies here would reform and build on existing institutions as well as create new ones by drawing on the best practices in leading institutions in India and other countries.
A Positive Psychology Perspective on Mate Preferences in the United States and Russia
Authors: Pearce Amy R. , Chuikova Tatyana , Ramsey Alexandra , Galyautdinova Svetalana
Published: May 2010

The authors collected and compared preference data on characteristics desired in long-term romantic partners between college students in two diverse countries, the United States and Russia. Based on evolutionary perspectives,the authors predicted that participants representing different cultures would retain certain adaptive gender differences. In addition, the authors included other attributes as potentially desirable in a long-term partner from studies within the field of positive psychology and predicted that these character strengths and virtues would feature prominently. Results suggested that the positive internal states of love, happiness, and kindness were among the most important qualities desired in a long-term romantic partner by both Russians and Americans. Gender differences were revealed for preferences in partner age and physique in both cultures as well as positive psychology’s traits of gratitude for Russians and forgiveness in the American sample. Overall, positive internal attributes were rated as highly important and the authors recommend these should be more fully considered in future studies on mate preferences.
Changing Boundaries of Ethnic Identity and Feelings Toward Ingroup/ Outgroup: Examining Taiwan Residents From a Psycho-Historical Perspective
Authors: Lee I-Ching , Pratto Felicia
Published: May 2010

Subjective group identification may not always be based on common biological origins or group salience, but rather, due to changes in group power. The present cross-temporal meta-analysis documents the transformation of Taiwan residents’ identification as both Taiwanese and Chinese during recent decades, in which the legitimacy of Chinese power over Taiwan was changed. The relations between identification and feelings toward Taiwanese and Chinese were also examined. Results suggest that historical memories and the political ascendancy of Taiwanese culture, rather than relative size of groups, increased identification with Taiwanese over Chinese. Historical and ethnic differences are compared to address ingroup favoritism, outgroup derogation, and other issues in social identity theory.
Supporter of stability or agent of agitation? The effect of US foreign policy on coups in Latin America, 1960—99
Authors: Thyne Clayton L
Published: May 2010

This article takes a two-step approach to improving our understanding of how US foreign policy signals affect the likelihood of coups in Latin America. First, a large body of qualitative literature has developed a ‘conventional wisdom’ on this subject, suggesting that pressure from the USA plays a key role in stabilizing favored leaders and destabilizing unfavored leaders. Meanwhile, quantitative scholarship analyzing coups focuses almost exclusively on intrastate factors. The first step brings these two bodies of work together by providing quantitative evidence that hostile US signals increase the likelihood of coups, while supportive signals have a stabilizing effect. The second step moves beyond the conventional wisdom by (1) reconsidering theoretical assumptions within the conventional argument and (2) identifying anomalies within the preliminary empirical analyses. These efforts reveal several factors that are likely to impact how coup plotters respond to US signals. Among these factors, empirical analyses indicate that US signals are particularly important when economic dependence on the USA increases, during the middle of a US president’s term in office, when they have moderate levels of consistency, and when they specifically mention the military. Overall, the first stage of this article provides a robust confirmation of the conventional wisdom, while the second stage moves the literature down a path that is largely unexplored by previous work.
Outsourcing Decisions, Product Innovation and the Spatial Dimension: Evidence from the Spanish Footwear Industry
Authors: Belso-Martinez Jose A.
Published: May 2010

Recent studies in developed countries frequently emphasise the importance of outsourcing as a strategy for manufacturing industries to survive. However, there is little qualitative evidence that specifically describes outsourcers in mature industries with competitive problems, particularly in southern Europe. This paper attempts to fill this gap by investigating the distinctive traits of firms located in the most important Spanish footwear industrial districts. From a sample of 401 Spanish firms surveyed in January and February 2006, it was found that size, design and product innovation, prior institutional networks and location in specific industrial districts favour the development of outsourcing strategies. By contrast, clients’ prior networks are negatively related with contracting-out productive activities. These results are relevant in several dimensions. However, the positive impact of some districts in the externalisation decision should be specifically mentioned. Such evidence seems to: confirm the consistency of the competition—co-operation dynamics in some geographical areas and the decline of others; and point out the existence of divergences in the outsourcing strategies at district level due to product and market characteristics.
Use of the proportion of patients dying on an End of Life Pathway as a quality marker: considerations for interpretation
Authors: Pugh Edwin J , McEvoy Mel , Blenkinsopp John
Published: May 2010

The Department of Health as part of its End of Life Care Strategy has developed a set of markers as a quality of care proxy for adults at the end of life. ‘The number/proportion of patients dying with the Liverpool Care Pathway (or equivalent) in place’ is suggested as a quality metric for all care providers. A retrospective audit of uptake of use of the Liverpool Care Pathway (LCP) in an NHS hospital in the North of England showed that 39% of all patients who died had been placed on the LCP. Overall 58% of patients who died were judged to meet the criteria for LCP use. This represented 81% of patients dying with cancer as a primary cause compared to 51% of patients dying with non-cancer. This difference was statistically very significant. In the Trust under study, 67% of dying patients who fulfilled the LCP criteria were placed on the pathway. The results of this study suggest that a simple percentage of deaths on the pathway is an unsophisticated statistic which needs to be interpreted with care. In particular it will be influenced by the proportion of people dying with cancer or non-cancer. This should be considered particularly when presenting the results to the public and to healthcare stakeholders or when making comparisons between provider organizations.