bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliative Chemotherapy Does Not Improve Survival in Metastatic Esophageal Cancer
Authors: Adenis Antoine , Penel Nicolas , Horn Samy , Dominguez Sophie , Vanhuyse Marie , Mirabel Xavier
Published: November 2010

Background: The role of chemotherapy in metastatic esophageal carcinoma (MEC) remains a matter of debate. The aim of this retrospective study was to analyze the survival impact of chemotherapy after stratification for prognostic factors. Methods: Consecutive patients with MEC (1995 to 2008) were randomly assigned to a development (n = 171) and a validation cohort (n = 113). We had first identified prognostic factors using the Kaplan-Meier and Cox methods in the development cohort and then validated them in the validation cohort. Then, we analyzed the impact of chemotherapy after stratification for these prognostic factors. The majority of patients had squamous cell carcinoma (80%). Results: The Cox model has retained 2 prognostic factors only: associated cancers (hazard ratio = 2.77, range 1.39–5.54, p = 0.004) and grade 3–4 dysphagia (hazard ratio = 1.44, range 1.08–2.14, p = 0.007). Median survival was 10.9 in patients with 0 (n = 77), 6.2 in those with 1 (n = 65) and 1.8 months in those with 2 prognostic factors (n = 11/171; p = 0.025). The median survival times of the patients with 0, 1 and 2 prognostic factors were 13 versus 9 months (nonsignificant, NS), 6 versus 5 months (NS) and 5 versus 1.3 months (NS) in patients with and without chemotherapy, respectively. Conclusion: Our data suggest that chemotherapy has no significant effect on survival for unselected MEC patients, regardless of the prognostic factors we identified.
Psychometric Validity of the Strengths and Difficulties Questionnaire-Dysregulation Profile
Authors: Holtmann Martin , Becker Andreas , Banaschewski Tobias , Rothenberger Aribert , Roessner Veit
Published: November 2010

Background: In many severely mentally disordered children, the clinical presentation is complicated by comorbid affective and behavioral dysregulation. Recently, a highly heritable behavioral phenotype of simultaneous deviance on the anxious/depressed, attention problems, and aggressive behavior syndrome scales has been identified on the Child Behavior Checklist Dysregulation Profile (CBCL-DP). The aim of the present pilot study was to determine an equivalent to the CBCL-DP using the Strengths and Difficulties Questionnaire (SDQ). Sampling and Methods: We applied stepwise linear discriminant analyses and receiver operating characteristic (ROC) analysis to data from 543 consecutively referred children and adolescents, aged 5–17 years. The CBCL and the SDQ were completed by parents as part of the diagnostic routine. ICD-10 discharge diagnoses were established in consensus conferences. Results: A combination of five SDQ items (SDQ-Dysregulation Profile, SDQ-DP) yielded the best discrimination of children with and without CBCL-DP and classified 81.0% of the subjects correctly leading to an area under the curve of 0.93. The content of the five SDQ-DP items mirrors well the mixed behavioral phenotype of anxious-depressive, aggressive and attention problems captured by the CBCL-DP. SDQ-DP status was highly correlated with CBCL-DP status and was best defined by a SDQ-DP score ≧5. Conclusions: The psychometric properties of the SDQ-DP have been robustly tested and validated. Based on these results, clinicians may use the SDQ-DP as a useful and economical screening measure to improve the assessment, prevention, and treatment of severe dysregulation in childhood and adolescence. Future investigations should study the longitudinal stability, heritability, and genetic associations of this behavioral phenotype.
Expression of Estrogen Receptor Beta and Phosphorylation of Estrogen Receptor Alpha Serine 167 Correlate with Progression-Free Survival in Patients with Metastatic Breast Cancer Treated with Aromatase Inhibitors
Authors: Motomura Kazuyoshi , Ishitobi Makoto , Komoike Yoshifumi , Koyama Hiroki , Nagase Hideki , Inaji Hideo , Noguchi Shinzaburo
Published: November 2010

Aromatase inhibitor (AI) is widely used as an endocrine treatment in postmenopausal patients with hormone receptor-positive breast cancer. To identify useful prognostic factors for patients with metastatic breast cancer treated with AI therapy, we investigated the association between several hormone receptor-related factors and prognosis. The expressions of estrogen receptor-α (ERα), ERβ, progesterone receptor, the phosphorylation of ERα serine 118 (Ser118) and ERα Ser167 were examined using immunohistochemical techniques for the primary tumors of 41 patients with metastatic breast cancer who received first-line AI therapy after relapse. To assess the associations of protein expression and phosphorylation levels with progression-free survival (PFS), the levels of each factor were categorized into low and high values at optimal cutoff points. In univariate analysis, high ERα expression and high ERα Ser167 phosphorylation correlated with longer PFS (p = 0.016 and 0.013, respectively). In multivariate analysis, low ERβ expression and high ERα Ser167 phosphorylation correlated with longer PFS (p = 0.031 and 0.004, respectively). Patients with both low ERβ expression and high ERα Ser167 phosphorylation had longer PFS than the others (p = 0.0107). These data suggest that the expression of ERβ and phosphorylation of ERα Ser167 may be useful prognostic factors in patients with metastatic breast cancer who received first-line AI therapy.
Safety and Feasibility of Using Sorafenib in Recurrent Hepatocellular Carcinoma after Orthotopic Liver Transplantation
Authors: Kim Richard , El-Gazzaz Galal , Tan Ann , Elson Paul , Byrne Michael , Chang Young Doo , Aucejo Federico
Published: November 2010

Background and Aim: The majority of patients who undergo orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have a very good prognosis if the tumor is within the Milan criteria. However, 10–15% of patients will have reoccurrence after OLT. Currently, sorafenib is available for advanced HCC. The safety and efficacy of sorafenib in this population has not been reported. Methods: We retrospectively looked at 54 patients who received sorafenib for advanced HCC. Out of 54 patients, we analyzed 9 who received sorafenib after OLT for HCC reoccurrence at Cleveland Clinic. Result: The median age at the time treatment with sorafenib was initiated was 59 years (range 46–77). Two patients received prior local therapy. Most of the toxicity was expected side effects from sorafenib except in 1 patient who developed hematological toxicity. Six patients required dose reduction secondary to toxicity. There were no unexpected complications from interaction with immunosuppressive medication. One patient achieved complete radiographic remission. Median survival from the start of sorafenib had not been reached at the time of writing; however, the 4-month survival rate is currently estimated to be 84 ± 15%, and 1 patient with lung reoccurrence has been treated for almost 18 months thus far. Conclusion: Sorafenib can be used in patients with recurrent HCC after liver transplantation with tolerable toxicity; however, dose adjustment may be required. A larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients.
Antifibrotic Effects of Pioglitazone at Low Doses on the Diabetic Rat Kidney Are Associated with the Improvement of Markers of Cell Turnover, Tubular and Endothelial Integrity, and Angiogenesis
Authors: Toblli Jorge E. , Cao Gabriel , Giani Jorge F. , Angerosa Margarita , Dominici Fernando P. , Gonzalez-Cadavid Nestor F.
Published: November 2010

Background/Aims: Pioglitazone and other thiazolidinediones are renoprotective in diabetic nephropathy at doses that normalize glycemia, presumably as a consequence of glycemic control. However, low doses of pioglitazone that did not normalize glycemia in rat models of type 2 diabetes prevented tubulointerstitial fibrosis and glomerulosclerosis through counteracting inflammation, oxidative stress, cell cycle arrest, and fibrosis. The current work tested whether this low-dose treatment also reduces other fibrosis and inflammation factors in the diabetic kidney and prevents tubular cell loss, endothelial damage, and abnormal angiogenesis. Methods: ZDF fa/fa rats (ZDF) were fed for 4 months chow with 0.001% pioglitazone, and the untreated ZDF and the non-diabetic lean Zucker rats (LZR) received regular chow. Proteinuria, creatinine clearance, blood pressure, and renal quantitative histopathology markers were determined. Results: Correction of renal function in ZDF by pioglitazone, occurring with a glycemia >250 mg/dl, was accompanied by normalization of the renal levels of connective tissue growth factor and fibronectin (fibrosis), TNF-α, interleukin-6 and MCP-1 (inflammation), megalin (tubular cells), the PCNA/caspase-3 ratio (positive cell turnover), VEGF (abnormal angiogenesis), and the ratio between eNOS and iNOS (endothelial dysfunction). Conclusion: This supports mechanisms for the renoprotective effects of pioglitazone in diabetes additional to glycemic control.
CCN2 (CTGF) Gene Polymorphism Is a Novel Prognostic Risk Factor for Cardiovascular Outcomes in Hemodialysis Patients
Authors: Cozzolino Mario , Biondi Maria Luisa , Banfi Elena , Riser Bruce L. , Mehmeti Florjan , Cusi Daniele , Gallieni Maurizio
Published: November 2010

Background: The very high cardiovascular (CV) mortality and morbidity rates in hemodialysis (HD) patients are greatly related to atherosclerosis. CCN2 (connective tissue growth factor/CTGF) is a profibrotic factor that is secreted by endothelial cells, involved in atherogenesis, promoting fibroblast proliferation and matrix production. CCN2 protein is significantly increased in complicated fibrous plaques and enhances monocyte migration into atherosclerotic lesions. The aim of this study was to investigate a possible association between CCN2 gene polymorphism and CV morbidity and mortality in HD patients. Methods: 98 HD patients, followed for 24 months, were genotyped for the common polymorphism on the CCN2 gene (G-945C). HD patient characteristics were: age 64 ± 13 years, males 64%, diabetes 24%, hypertension 62%, smokers 38%, dyslipidemia 28%, all undergoing standard HD three times weekly. Results: All-cause mortality was not associated with CCN2 polymorphism (G-945C). In contrast, however, the GG genotype was strongly associated with CV mortality: OR 13 (1.49–155), p = 0.0048. Interestingly, the GG genotype was also greatly associated with the serious CV events of stroke and myocardial infarction in surviving HD patients: OR 13.3 (2.5–87.08), p = 0.0001. Conclusions: We demonstrate for the first time that CCN2 gene polymorphism is a prognostic risk factor for CV morbidity and mortality in HD patients. These data may have important implications for better understanding the link between accelerated atherosclerosis and increased mortality in HD population.
Assessment of Eptifibatide Clearance by Hemodialysis Using an in vitro System
Authors: Hudson Joanna Q. , McNeely Elizabeth B. , Green Christie A. , Jennings Lisa K.
Published: November 2010

Background/Aims: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor that prevents platelet aggregation. Although contraindicated in dialysis patients due to limited safety and dialysis data, eptifibatide is prescribed in this population and is associated with bleeding complications. This study was done to determine dialysis clearance (CLD) of eptifibatide using an in vitro system. Methods:Three common dialyzers were tested. In vitro dialysis was performed at a dialysate flow rate of 500 ml/min, ‘blood’ flow rate (QB) of 200 and 400 ml/min, and the minimal ultrafiltration rate. Eptifibatide CLD and fraction removed were calculated for each condition. Results: CLD ranged from 122 to 225 ml/min and was not significantly different among the dialyzers tested. CLD was flow dependent with higher clearances observed at higher QB. The estimated fraction of eptifibatide removed was 73–83%. Conclusions: These data suggest that hemodialysis is an effective method to decrease the effects of eptifibatide in patients with impaired kidney function.
Genetics in Clinical Practice: Nephrotic and Proteinuric Syndromes
Authors: McCarthy Hugh J. , Saleem Moin A.
Published: November 2010

Nephrotic syndrome (NS) is a disorder of the glomerular filtration barrier, a highly specialised tri-layer structure with unique functional properties. Recent advances emanating from the field of molecular genetics have revealed the podocyte as probably the central player in the control of glomerular filtration. More specifically, the cell–cell junction between adjacent podocyte foot processes, the slit diaphragm, has been revealed to be made up of a sophisticated multi-protein complex which dynamically controls foot process architecture via signalling to the actin cytoskeleton. Key genes that have been identified from the study of inherited NS include those encoding nephrin, podocin, TRPC6 and α-actinin-4, and more remain to be found. It is now possible to identify genetic causes underlying a proportion of NS presenting at any age, and this review aims to help describe genetic NS according to age of presentation, and provide information on known mutations. The next big challenge for clinicians and researchers is to translate the molecular information learnt into the understanding of acquired, non-inherited forms of the disease.
Disorders of Calcium Metabolism
Authors: O’Toole John F.
Published: November 2010

The genetic contribution to calcium metabolism is well recognized. Many of the proteins that contribute to calcium homeostasis through intestinal absorption, bone deposition and resorption, renal reabsorption and the molecules regulating these processes have been identified. Mutations in many of the genes coding for these proteins have been identified and often have clear clinical phenotypes. These mutations are generally rare with large effect sizes and a high degree of penetrance. As monogenetic diseases, they have a mendelian inheritance pattern and have been identified with traditional family-based linkage studies. A great deal of progress has been made in the understanding of the physiology of calcium metabolism; however, it remains an evolving field. The identification of the monogenetic etiology of disease has contributed greatly to our understanding of calcium handling and homeostasis. Transgenic animal models of these diseases continue to offer new insights into the mechanisms of calcium metabolism and its regulation. The purpose of this review is to briefly outline calcium metabolism focusing on the mechanisms of intestinal absorption and renal reabsorption as a framework to review the monogenic causes of dysregulated calcium metabolism.
Disorders of Water and Acid-Base Homeostasis
Authors: Karet Fiona E.
Published: November 2010

Disorders of water balance lead either to dehydration or overhydration. Because there is an intimate relationship between water and sodium concentration (water generally following salt), one can distinguish hypotonic, isotonic and hypertonic dehydration and the same for overhydration. The vast majority of water balance disorders are acquired. In this article, the focus is on the inherited disorders both of water (nephrogenic diabetes insipidus) and acid-base balance. Both acidosis and alkalosis can arise from primary tubular ion transport abnormalities. The alkaloses are usually secondary to salt handling problems, whereas the renal tubular acidoses are often a consequence of primary abnormalities of acid-base transporters.
Genetics of Familial Renal Cancers
Authors: Maher Eamonn R.
Published: November 2010

Renal cell carcinoma (RCC) is a heterogeneous disorder. A variety of histopathological subtypes occur, and the molecular mechanisms associated with these subtypes can differ. Only a small fraction of all RCC is accounted for by inherited cases (e.g. von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary leiomyomatosis renal cell cancer), but such cases can pose specific clinical management issues and offer opportunities for early cancer detection and prevention. Furthermore, inherited RCC syndromes have provided important paradigms to study the molecular basis of renal tumourigenesis. The identification of molecular mechanisms of carcinogenesis in inherited RCC syndromes should lead to novel approaches to personalized therapeutics.
Haemolytic Uraemic Syndrome
Authors: Kavanagh David , Goodship Tim
Published: November 2010

Atypical haemolytic uraemic syndrome (aHUS) is a disease characterized by complement overactivation in which inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Identification of the underlying defect can both predict disease outcome and guide treatment. The ability to remove inhibitory autoantibodies and hyper-active complement components in addition to its ability to replace defective complement regulators means that plasma exchange is currently first-line therapy. In those with factor H and factor I mutations who do progress to end-stage renal failure, renal transplantation usually fails due to recurrent HUS. In this situation, combined liver-kidney transplantation has been suggested to correct the underlying genetic defect. Newer agents, such as the complement inhibitor eculizumab, may herald a new era in the treatment of aHUS.
Blood Pressure, Proteinuria and Nephropathy in Fabry Disease
Authors: Jain Gaurav , Warnock David G.
Published: November 2010

Background/Aims: Fabry disease is an X-linked disorder leading to abnormal accumulation of glycosphingolipids with multisystem involvement, including cardiac, renal, dermatologic and neurologic manifestations. Fabry nephropathy, specifically proteinuria and progressive chronic kidney disease, have taken center stage over the past decade, defining disease outcomes as well as mortality associated with Fabry disease. Systemic blood pressure among patients with Fabry disease is relatively low, compared to other forms of proteinuric chronic kidney disease. Methods: This review is based on a systematic survey of recent publications that describe the diagnosis and treatment of Fabry nephropathy in adults. Results: A high percentage of patients with Fabry disease have been shown to have proteinuria, and a small but significant percentage of Fabry patients have overt hypertension. Recent efforts have focused on the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEIs/ARBs) in addition to enzyme replacement therapy (ERT) for treatment of Fabry nephropathy. The proven beneficial effects of ACEI/ARBs for more common forms of proteinuric kidney disease have been extrapolated to the treatment of Fabry nephropathy. The overall treatment goal with ACEIs/ARBs, in combination with ERT, is reduction of urinary protein excretion to less than 500 mg/day, and stabilization of the decline of kidney function to –1 ml/min/1.73 m2/year. ERT alone, in the absence of ACEIs/ARBs does not decrease proteinuria in Fabry patients. We present the prevalence of proteinuria, kidney disease and hypertension in Fabry disease and discuss treatment goals for the treatment of this unusual form of proteinuric kidney disease. Conclusion: There are some practical challenges to the use of standard antiproteinuric therapy in Fabry disease that need to be addressed to optimize patient outcome, with the expectation that kidney function can be preserved with the combination of ERT and ACEI/ARB therapy.
Characterization of Dental Pulp Stem Cells from Impacted Third Molars Cultured in Low Serum-Containing Medium
Authors: Karbanová Jana , Soukup Tomáš , Suchánek Jakub , Pytlík Robert , Corbeil Denis , Mokrý Jaroslav
Published: November 2010

We isolated and expanded stem cells from dental pulp from extracted third molars using an innovative culture method consisting of low serum-containing medium supplemented with epidermal growth factor and platelet-derived growth factor BB. We evaluated the differentiation potential of these cells when they were growing either adherently or as micromass/spheroid cultures in various media. Undifferentiated and differentiated cells were analyzed by flow cytometry, immunocytochemistry and immunoblotting. The flow cytometry results showed that the dental pulp stem cells (DPSCs) were positive for mesenchymal stromal cell markers, but negative for hematopoietic markers. Immunocytochemical and/or immunoblotting analyses revealed the expression of numerous stem cell markers, including nanog, Sox2, nestin, Musashi-1 and nucleostemin, whereas they were negative for markers associated with differentiated neural, vascular and hepatic cells. Surprisingly, the cells were only slightly positive for α-smooth muscle actin, and a heterogeneous expression of CD146 was observed. When cultured in osteogenic media, they expressed osteonectin, osteopontin and procollagen I, and in micromass cultures, they produced collagen I. DPSCs cultured in TGF-β1/3-supplemented media produced extracellular matrix typical of cartilaginous tissue. The addition of vascular endothelial growth factor to serum-free media resulted in the expression of endothelial markers. Interestingly, when cultured in neurogenic media, DPSCs exhibited de novo or upregulated markers of undifferentiated and differentiated neural cells. Collectively, our data show that DPSCs are self-renewing and able to express markers of bone, cartilage, vascular and neural tissues, suggesting their multipotential capacity. Their easy accessibility makes these cells a suitable source of somatic stem cells for tissue engineering.
Disposition and Metabolism of Ralfinamide, a Novel Na-Channel Blocker, in Healthy Male Volunteers
Authors: Bauer M. , Bliesath H. , Leuratti C. , Lackner E. , Dieterle W. , Müller M. , Brunner M.
Published: November 2010

Ralfinamide is an α-aminoamide derivative with ion channel blocking properties, acting both peripherally and centrally through different molecular targets important in pain control. Absorption, blood and plasma time courses, and urinary and faecal excretion of total radioactivity were assessed in 6 male healthy volunteers administered a single oral dose of 320 mg 14C-(S)-ralfinamide. Pharmacokinetics of the parent drug were investigated over 120 h, urinary and plasma metabolites up to 192 h post-dose. 14C-(S)-ralfinamide was rapidly and completely absorbed. Ralfinamide and the dealkylated ralfinamide metabolite (NW-1716) represented the majority of plasma radioactivity. Plasma elimination of the parent compound occurred mono-exponentially (half-life approx. 15 h). 14C-radioactivity was eliminated in a bi-phasic manner (terminal half-life of 60 and 24 h for plasma and whole blood, respectively). Plasma-concentrations of unchanged ralfinamide were significantly lower than radioactivity concentrations, indicating metabolism of the parent compound. At 192 h post-dose the total balance of radioactivity was almost complete (95%). The main route of excretion was via the kidneys (94% of the dose). Major metabolites identified in urine and plasma were the N-dealkylated acid of ralfinamide and deaminated ralfinamide acid (NW-1799). Other metabolites, in particular the product of glucuronide conjugation N-dealkylated-β-glucuronide, were identified.
Pifithrin-α, an Inhibitor of p53 Transactivation, Up-Regulates COX-2 Expression through an MAPK-Dependent Pathway
Authors: Kim Sangmin , Han Jeonghun , Lee Se Kyung , Hur Sung Mo , Koo Minyoung , Cho Dong Hui , Bae Soo Youn , Choi Min-Young , Shin Incheol , Yang Jung-Hyun , Nam Seok Jin , Lee Jeong Eon
Published: November 2010

Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers, including breast and colorectal cancers, resulting in accumulation of prostaglandin E2 in the cancer cell environment. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53 transactivation, on COX-2 expression in breast and fibrosarcoma cells. Our results showed that COX-2 expression was dose-dependently increased by PFT-α in MDA-MB231 breast cancer cells with mutant p53. In addition, the expression level of COX-2 was also increased by PFT-α in normal fibroblasts as well as in HT1080 fibrosarcoma cells with p53 wild-type cells. To verify the regulatory mechanism of COX-2 in response to PFT-α, we pretreated cells with a mitogen-activated protein kinase (MAPK) kinase (MEK)1/2 inhibitor (UO126) and a phosphoinositide-3 (PI-3K) inhibitor (LY294002). PFT-α-induced COX-2 expression was significantly decreased by UO126 and LY294002 in MDA-MB231 cells. However, the phosphorylation of extracellular signal-regulated kinase (ERK) was increased by PFT-α, but not Akt phosphorylation. Finally, we confirmed the correlation of the MEK and PI-3K pathway and COX-2 expression using the constitutively active (CA)-MEK and myr-Akt adenovirus systems. COX-2 expression was increased by CA-MEK transfection, but not by myr-Akt. Taken together, we have demonstrated that PFT-α-induced COX-2 expression is regulated through a MEK/ERK pathway in MDA-MB231 human breast cancer cells.
Estimation of Oxidative Stress Markers in Chronic Kidney Disease
Authors: Kuchta Agnieszka , Pacanis Anastasis , Kortas-Stempak Barbara , Çwiklińska Agnieszka , Ziętkiewicz Marcin , Renke Marcin , Rutkowski Boleslaw
Published: November 2010

Changes mediated by oxidative stress are thought to be involved with atherosclerosis in patients with chronic kidney disease (CKD). The purpose of this study was to analyze the markers of oxidative damage and the activity of antioxidative enzymes as well as the total antioxidant capability in patients with different stages of CKD, both conventionally treated and dialyzed. We evaluated the oxidative modification of lipids (by oxidized low-density lipoprotein and malonodialdehyde levels) and proteins (by advanced oxidation protein products level). We also assessed the activity of paraoxonase-1 and glutathione peroxidases and total antioxidant status. Compared with the control group, the uremic patients, both dialyzed and nondialyzed, had higher levels of all studied plasma oxidative stress markers and decreased activity of antioxidative enzymes. Our results lead us to conclude that oxidative stress seems to be related rather to the uremic state than to the dialysis treatment. We also showed that estimating total antioxidant status in a simple test is unreliable for assessing the antioxidant ability of patients with CKD.
How Useful Is the IQCODE for Discriminating between Alzheimer’s Disease, Mild Cognitive Impairment and Subjective Memory Complaints?
Authors: Sikkes Sietske A.M. , van den Berg Mark T. , Knol Dirk L. , de Lange-de Klerk Elly S.M. , Scheltens Philip , Uitdehaag Bernard M.J. , Klein Martin , Pijnenburg Yolande A.L.
Published: November 2010

Background: Informant questionnaires may be useful in diagnosing early dementia. Conflicting results were found when these questionnaires were used to differentiate patients with mild cognitive impairment (MCI) from healthy elderly subjects. We evaluated the ability of the most commonly used informant questionnaire, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), to discriminate between Alzheimer’s disease (AD), MCI and subjective memory complaints (SMC). Methods: Informants of 180 AD patients, 59 MCI patients and 89 SMC subjects who visited the Alzheimer Center of the VU University Medical Center between 2004 and 2007 completed the short Dutch version of the IQCODE. Logistic regression and receiver operating characteristic curves were used to evaluate the diagnostic ability of the IQCODE. Results: The IQCODE was able to differentiate AD from MCI and SMC, but was not able to differentiate SMC from MCI. Conclusions: The IQCODE may be helpful in diagnosing AD but is of limited use in differentiating MCI from SMC.
Chronic Nitric Oxide Deficiency and Progression of Kidney Disease after Renal Mass Reduction in the C57Bl6 Mouse
Authors: Muller Veronika , Tain You-Lin , Croker Byron , Baylis Chris
Published: November 2010

Background/Aims: The C57Bl6 mouse is resistant to chronic kidney disease (CKD) induced by reduction of renal mass (RRM). Nitric oxide (NO) deficiency exacerbates CKD progression so this study investigated whether combination of RRM and NO deficiency would render the C57Bl6 mouse vulnerable to CKD. Methods: We used wild-type (WT) mice with RRM, chronic NO synthase (NOS) inhibition and a combination. Also, endothelial NOS (eNOS) knockout (KO) C57Bl6 mice were studied with and without RRM. Primary endpoints were albuminuria and structural damage. Results: Both nonselective (+L-NAME) and neuronal NOS ‘selective’ (+7NI) NOS inhibition greatly exacerbated the albuminuria and structural damage seen with RRM in the WT mice; NOS inhibition alone had little effect. The eNOS KO mice showed marked structural damage and significant albuminuria in the shams and RRM produced minimal exacerbation of structural damage although the albuminuria was massively amplified. Conclusion: These studies demonstrate that the C57Bl6 mouse is rendered vulnerable to RRM-induced CKD when concomitant NO deficiency is produced. This observation supports previous work in CKD-resistant rats and suggests that NO deficiency is required for progression of CKD.
WNT Signaling in Adult Cardiac Hypertrophy and Remodeling
Authors: Bergmann Martin W.
Published: November 2010

On pathological stress, the heart reactivates several signaling pathways that traditionally were thought to be operational only in the developing heart. One of these pathways is the WNT signaling pathway. WNT controls heart development but is also modulated during adult heart remodeling. This review summarizes the currently available data regarding WNT signaling during left ventricular (LV) remodeling. Upstream, soluble frizzled-related proteins (sFRPs) block WNT-dependent activation of the canonical WNT pathway. By inhibition of WNT activation, these factors also reduce β-catenin–dependent transcription by altering the ratio of cytoplasmic/nuclear β-catenin. In experimental settings, sFRPs injected into the heart attenuated LV remodeling. sFRPs are secreted from autologous bone marrow–derived mononuclear cells. Disheveled is a signaling intermediate of both the canonical and noncanonical WNT pathway. Similarly to the effect of sFRP, depletion of a disheveled isoform attenuated LV remodeling. In contrast, disheveled activation led to progressive dilated cardiomyopathy. Inhibition of nuclear β-catenin signaling downstream of the canonical WNT pathway significantly reduced postinfarct mortality and functional decline of LV function following chronic left anterior descending coronary artery ligation. WNT signaling also affects mobilization and homing of bone marrow–derived vasculogenic progenitor cells. Finally, heart-specific WNT/β-catenin interaction partners have been identified that will possibly allow targeting this pathway in a tissue-specific manner. In summary, the WNT pathway plays a pivotal role in adult cardiac remodeling and may be suitable for therapeutic interventions. Currently, several molecular and cellular mechanisms whereby WNT inhibition attenuates LV remodeling are proposed. Reactivation of the developmental program to restore functional LV myocardium from resident precursor cells may significantly contribute to this process.
Biology of Endoplasmic Reticulum Stress in the Heart
Authors: Groenendyk Jody , Sreenivasaiah Pradeep Kumar , Kim Do Han , Agellon Luis B. , Michalak Marek
Published: November 2010

The endoplasmic reticulum (ER) is a multifunctional intracellular organelle supporting many processes required by virtually every mammalian cell, including cardiomyocytes. It performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, posttranslational modification including
N
-linked glycosylation, and synthesis of phospholipids and steroids on the cytoplasmic side of the ER membrane, and regulation of Ca
2+
homeostasis. Perturbation of ER-associated functions results in ER stress via the activation of complex cytoplasmic and nuclear signaling pathways, collectively termed the unfolded protein response (UPR) (also known as misfolded protein response), leading to upregulation of expression of ER resident chaperones, inhibition of protein synthesis and activation of protein degradation. The UPR has been associated with numerous human pathologies, and it may play an important role in the pathophysiology of the heart. ER stress responses, ER Ca
2+
buffering, and protein and lipid turnover impact many cardiac functions, including energy metabolism, cardiogenesis, ischemic/reperfusion, cardiomyopathies, and heart failure. ER proteins and ER stress-associated pathways may play a role in the development of novel UPR-targeted therapies for cardiovascular diseases.
‘What’s Teleology Got To Do With It?’ A Reinterpretation of Aristotle’s Generation of Animals V
Authors: Gotthelf Allan , Leunissen Mariska
Published: November 2010

Despite the renewed interest in Aristotle’s Generation of Animals in recent years, the subject matter of GA V, its preferred mode(s) of explanation, and its place in the treatise as a whole remain misunderstood. Scholars focus on GA I-IV, which explain animal generation in terms of efficient-final causation, but dismiss GA V as a mere appendix, thinking it to concern (a) individual, accidental differences among animals, which are (b) purely materially necessitated, and (c) are only tangentially related to the topics discussed in the earlier books. In this paper, we defend an alternative and more integrated account of GA V by closely examining Aristotle’s methodological introduction in GA V.1 778a16-b19 and his teleological explanation of the differences of teeth in GA V.8. We argue for the unity of both GA V and of GA as a whole and present a more nuanced theory of teleological explanation in Aristotle’s biology.
At Play in the Field of Possibles
Authors: Zaner Richard M.
Published: November 2010

This essay focuses on questions central to Husserl’s essential methodology, specifically his notion of ‘free-fantasy variation,’ which he regarded as his ‘fundamental methodological insight.’ At the heart of this ‘vital element of phenomenology’ is what he often terms ‘as-if experience’ thanks to which anything whatever (actual or possible) can be considered either for its own sake or as an example of something else. Further analysis explores the act of exemplification, the act of feigning (termed possibilizing) and the shifts of attention and orientation that ground free-fantasy variation. Exemplification and possibilizing are then examined in daily life to discern what makes the complex act of feigning at all possible. An examination of the phenomenon of upsets (of what is typically expected) brings the core sense of possibilizing to light. A focus on the dramatic force intrinsic to these experiences, and the essential place of reflective awareness inherent to them, makes apparent how the rudimentary sense of self begins to emerge, and there follows an analysis of this self-referentiality of possibilizing. The analysis then concludes with a brief examination of Husserl’s so-called ‘zig-zag’ method of constitutive phenomenology.
Heidegger’s Nietzsche, the Doctrine of Eternal Return, and the Phenomenology of Human Finitude
Authors: Stolorow Robert D.
Published: November 2010

Nietzsche’s doctrine of the eternal return of the same, seen through the lens of Heidegger’s interpretation, captures the groundlessness of existence in a technological world devoid of normative significance. The author contends that the temporality depicted poetically in the thought of eternal return is the traumatic temporality of human finitude, to which Nietzsche was exposed at the age of 4 when the death of his father shattered his world. Nietzsche’s metaphysical position is seen as a metaphorical window into the phenomenology of finitude and of the struggle to overcome it.
Orthopraxy in Tannaitic Literature
Authors: Grossberg David M.
Published: November 2010

M. Sanhedrin 10:1 is well-known as a succinct statement of rabbinic doctrine. Yet as a statement of doctrine, this mishnah’s language is remarkably pragmatic: it proscribes saying certain things but does not explicitly proscribe believing them. I propose that this use of practical rather than doctrinal phraseology was an intentional editorial stance of the Mishnah’s compilers. A close philological examination of parallel texts in the Tosefta and Seder Olam reveals that earlier generations of the textual tradition underlying this mishnah phrased these same prohibitions using doctrinal terms such as “denying” or “not acknowledging.” Moreover, this choice of pragmatic language is evident throughout the Mishnah, even when fundamentals of Judaic faith such as belief in one God and in the oral Torah are being addressed. The Mishnah’s compilers, perhaps in response to trends like early Christian antinomianism and heresiology, chose to produce a work dedicated to orthopraxy rather than orthodoxy.
The Title Ethnarch in Second Temple Period Judea
Authors: Sharon Nadav
Published: November 2010

The title Ethnarch appears in Second Temple sources in reference to four Judean rulers: Simon the Hasmonean, John Hyrcanus, Hyrcanus II, and Archelaus, son of Herod. This evidence is usually taken for granted. However, a meticulous analysis of the sources shows that we should not rely on the evidence pertaining to the early Hasmoneans (Simon and John Hyrcanus), and it rather seems that the title was first employed only by the Romans (probably Julius Caesar) for Hyrcanus II. The paper further asserts that this title exemplifies a unique perception of the Jewish people by the Romans. Additionally, the paper notes some ramifications that this understanding of the title Ethnarch and the view which it exemplifies may have on certain issues of the Second Temple period.*
The Limitations on Critical Thinking on Religious Issues under Article 20 of ICCPR and its Relation to Freedom of Expression
Authors: Eltayeb Mohamed Saeed M.
Published: November 2010

This article aims at examining the admissible scope of limitations on critical thinking on religious issues and the circumstances under which criticism of a religion may fall within the scope of Article 20 of the ICCPR. What does this imply in relation to freedom of expression, in particular artistic freedom? To what extent does the promotion of freedom of expression require States to punish advocacy of religious hatred which constitutes incitement to discrimination, hostility or violence? The main premise of the article is that the questions mentioned above should be seen in terms of the balance and complementarity of competing rights, namely, the right to freedom of religion and respect for human dignity of believers vis-à-vis the right to freedom of expression. This balance cannot invariably be set for all places, but should instead be maintained taking into account the historical experiences and local conditions. Furthermore, the article argues that the right to freedom of expression is not absolute and that international human rights law affirms certain restrictions on exercising this right. The question, however, of where to draw the boundaries between the right to freedom of expression and advocacy of religious hatred that constitutes incitement to discrimination, hostility or violence can best be answered contextually and with due regard to, inter alia, local conditions, history, culture and political tensions.
Limits to the Restrictions to Freedom of Expression—Criteria and Application
Authors: Schmidt Mogens
Published: November 2010

The freedoms of opinion and of expression constitute the cornerstone of any democratic society and form a solid and fundamental basis for development. Without an open space for the marketplace of ideas to flourish, societies fail to progress by any measure on the human, social, and economic development scale. Given the paramount importance of this fundamental right, restrictions on freedom of expression, in order to be permissible, must be narrowly defined and will have to be derived from the relevant international legal standards. In this context it is equally important to note that there is no a priori hierarchy of rights.
Exploring touch as a positive workplace behavior
Authors: Fuller Bryan , Simmering Marcia J , Marler Laura E , Cox Susie S , Bennett Rebecca J , Cheramie Robin A
Published: November 2010

Whereas most research has focused on the negative aspects of touch in the workplace (i.e. sexual harassment), this study focuses upon the positive use of touch. In an effort to explain individual differences in the use of workplace touch, three sequential studies are used to introduce the concepts of workplace touch self-efficacy and workplace touch initiation anxiety. In Study 1 we develop scales to assess the constructs. Study 2 provides an initial examination of the construct validity of the measures developed in Study 1. Results of Study 3 indicate that supervisor reports of touch self-efficacy and physiological touch anxiety are related to subordinate reports of supervisor touch. Additionally, results show that supervisor use of touch is related to several indicators of supervisor social effectiveness. Finally, sex of the supervisor appears to play a role in workplace touch as female supervisors report less touch anxiety, greater touch self-efficacy and more use of touch than male supervisors.
Diversity faultlines, shared objectives, and top management team performance
Authors: van Knippenberg Daan , Dawson Jeremy F , West Michael A , Homan Astrid C
Published: November 2010

Faultline theory suggests that negative effects of team diversity are better understood by considering the influence of different dimensions of diversity in conjunction, rather than for each dimension separately. We develop and extend the social categorization analysis that lies at the heart of faultline theory to identify a factor that attenuates the negative influence of faultlines: the extent to which the team has shared objectives. The hypothesized moderating role of shared objectives received support in a study of faultlines formed by differences in gender, tenure, and functional background in 42 top management teams. The focus on top management teams has the additional benefit of providing the first test of the relationship between diversity faultlines and objective indicators of organizational performance. We discuss how these findings, and the innovative way in which we operationalized faultlines, extend faultline theory and research as well as offer guidelines to manage diversity faultlines.
Contested terrain in careers: A psychological contract model
Authors: Inkson Kerr , King Zella
Published: November 2010

In this article we extend consideration of differences of interest in employment relationships to career issues. Two sets of interests — those of employing organizations and of individual workers — often make careers ‘contested terrain’ in which organizations pursue strategic advantages and individuals personal advantages. The contestation is contextualized by current trends to individualized employment relations and a focus on managerial, professional and technical work. The two interest sets mirror a disjuncture between two disciplinary bases, the ‘vocational’ base underpinned by psychology and the ‘strategic human resource management’ (SHRM) base, underpinned by economics. We develop a ‘psychological contract’ model, in which both individuals and organizations invest knowledge capital in the other with a view to obtaining long-term returns. We consider the implications of our analysis and model for career management by both individuals and organizations, for future research on careers, and for the interdisciplinary study of careers in an integrated ‘career studies’.
In search of the blue flower? Grand social theories and career research: The case of Bourdieu’s theory of practice
Authors: Chudzikowski Katharina , Mayrhofer Wolfgang
Published: November 2010

Responding to the various calls for more interdisciplinarity in career research over the last few decades, we identify five touchstones for theoretical concepts to advance the interdisciplinary dialogue on careers. Drawing on Bourdieu’s theory of practice, we outline its contributions to such a dialogue in the light of these touchstones. In spite of some potential pitfalls, the theory of practice not only invites interdisciplinary dialogue, but also provides a unifying framework for generating new questions in career research and systematically integrating concepts from other disciplines. Overall, this is but one example of how grand social theories can stimulate interdisciplinarity in career research.
Careers, social context and interdisciplinary thinking
Authors: Lawrence Barbara S
Published: November 2010

Scholars have engaged in studies of careers, individuals’ work experiences over time, since the early 20th century. Although much has been written about the need for interdisciplinary research, limited work exists. This article presents a comparative technique that facilitates interdisciplinary thinking. Using data from a large organization, three stories are applied to the associations between social context and career outcomes: a different disciplines story, a multiple disciplines story and an interdisciplinary story. The results suggest that the best career satisfaction outcome results from the multiple disciplines story, whereas the best performance and salary outcomes result from the interdisciplinary story.
Interdisciplinary approaches to contemporary career studies
Authors: Khapova Svetlana N , Arthur Michael B
Published: November 2010

This is the opening article in a Human Relations special issue on ‘Interdisciplinary approaches to contemporary career studies’. After introducing a story of an ‘exceptional — but real’ career, we argue for an urgent shift toward greater interdisciplinary inquiry. We reflect on the story to describe differences in the way each of psychology, sociology, social psychology, and economics views the concept of career. We turn to explore what career researchers, representing each of the above social sciences, might not see on their own. In contrast, we highlight how social scientists can move toward a) appreciating the limitations of our separate approaches, b) introducing more appropriate research methods, c) maintaining a wider cross-disciplinary conversation, and d) better serving the client — the person — in our future research. We continue with a preview of the remaining five articles in this special issue, and propose that these can serve as stimuli for a wider conversation.
Fiber-reinforced epoxy composites exposed to high temperature environments. Part II: modeling mechanical property degradation
Authors: Kandare Everson , Kandola Baljinder K. , McCarthy Edward D. , Myler Peter , Edwards Gerard , Yong Jifeng  , Wang Yong C.
Published: November 2010

This article is part of a series on the thermo-mechanical responses of fiber-reinforced composites at elevated temperatures and it follows the first part containing experimental results. A flame-retardant system consisting of a cellulosic charring agent and an interactive intumescent additive (melamine phosphate) has been used in order to improve the post-fire mechanical performance of glass fiber-reinforced epoxy composites. The effect of one-sided radiant heat on the residual flexural stiffness of laminate coupons exposed to incident heat fluxes of 25 and 35 kW m-2 was investigated. The flame-retarded coupons retained a higher percentage of their original room temperature flexural modulus after heat exposure while the control specimens showed inferior material property retention over the same exposure periods. A heat transfer (thermal) model based on Henderson’s equation is used to predict the through thickness temperature profiles and subsequently the mass loss due to the resin matrix decomposition at elevated temperatures. The theoretical results from the heat transfer model are validated against experimentally obtained data and then coupled with a mechanics model that describes material property-temperature dependence in order to predict the residual flexural stiffness, after heat damage. The accuracy of the thermo-mechanical model was validated against the experimental data and a good agreement was observed.