bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life of nursing‐home residents with dementia subject to surveillance technology versus physical restraints: an explorative study
Authors: te Boekhorst S. , Depla M. F. I. A. , Francke A. L. , Twisk J. W. R. , Zwijsen S. A. , Hertogh C. M. P. M.
Published: May 2012

Objective

As physical restraints should only be used in exceptional cases, there is an urgent need for alternatives to restraint use. Surveillance technology could be such an alternative. This study explored whether nursing‐home residents with dementia subjected to surveillance technology had better quality of life scores for mood, behavioral and societal dimensions than residents with physical restraints.

Methods

Quality of life was assessed longitudinally, with three measurements in six psychogeriatric nursing homes of residents with surveillance technology (n = 170) and residents with physical restraints (n = 22). QUALIDEM subscales were used to measure five dimensions of quality of life. Multilevel longitudinal univariate and multivariate regression techniques were used to analyze the data.

Results

Because physical restraints were almost exclusively used in residents with low activities of daily living (ADL) independency (18 of the 22), we restricted the regression analyses to residents with a Barthel Index score ≤ 5 (overall n = 53). Univariate results showed that highly ADL‐dependent residents with surveillance technology had significantly more positive affect than highly ADL‐dependent residents with physical restraints. However, this difference proved to be no longer significant after adjustment for the confounders: age, sex and stage of dementia.

Conclusions

Quality of life of highly ADL‐dependent nursing‐home residents with dementia seems to be unrelated to the use of surveillance technology as opposed to physical restraints. Copyright © 2012 John Wiley & Sons, Ltd.
Prognostic value of cetuximab‐related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: Results from a randomized trial of the GERMAN AIO CRC Study Group
Authors: Stintzing Sebastian , Kapaun Christine , Laubender Rüdiger Paul , Jung Andreas , Neumann Jens , Modest Dominik Paul , Giessen Clemens , Moosmann Nicolas , Wollenberg Andreas , Kirchner Thomas , Heinemann Volker
Published: May 2012

Skin toxicity is a frequent adverse event of epidermal growth factor receptor (EGFR) targeting agents. Occurrence of cetuximab‐induced skin toxicity (Cet‐ST) correlates with better treatment response and longer survival times. Molecular markers predicting Cet‐ST are still missing. This investigation analyzed the value of Cet‐ST for treatment efficacy in a randomized trial comparing cetuximab plus capecitabine/irinotecan to cetuximab plus capecitabine/oxaliplatin as first‐line treatment of metastatic colorectal cancer. Patient characteristics and molecular parameters (KRAS mutation, EGFR‐FISH, EGFR‐IHC and EGFR intron‐1 polymorphism) of the tumour were correlated with response and Cet‐ST. Cet‐ST grade 0–1 was observed in 31%, grade 2–3 in 69% of patients. Outcome favoured patients with grade 2–3 Cet‐ST with regard to overall response rate (62 vs. 41%), PFS (7.8 vs. 5.2 months) and overall survival (OS) (30.3 vs. 18.0 months). First‐cycle rash was observed in 66% of patients and corresponded with longer survival (30.7 vs. 20.2 months, p = 0.007). Patients without Cet‐ST had a poor outcome (PFS, 1.9 months; OS, 11 months). The correlation of Cet‐ST with survival was specifically evident in patients with KRAS codon‐12‐mutated tumours assumed to be cetuximab resistant. In multivariate analysis of patient characteristics, male gender and younger age were significantly correlated with Cet‐ST. Among molecular parameters, no significant correlation with Cet‐ST was found. Cet‐ST is an early predictor of treatment efficacy in cetuximab‐treated patients. This effect of Cet‐ST is independent of the KRAS mutation status, suggesting that Cet‐ST rather relates to constitutional factors of the patient than alterations of the EGFR pathway in the tumour.
Mitochondrial alteration in malignantly transformed human small airway epithelial cells induced by α‐particles
Authors: Zhang Suping , Wen Gengyun , Huang Sarah XL , Wang Jianrong , Tong Jian , Hei Tom K.
Published: May 2012

Human small airway epithelial cells (SAECs) immortalized with human telomerase reverse transcriptase were exposed to either a single or multiple doses of α‐particles. Irradiated cells showed a dose‐dependent cytotoxicity and progressive neoplastic transformation phenotype. These included an increase in saturation density of growth, a greater resistance to N‐phosphonoacetyl‐L‐aspartate, faster anchorage‐independent growth, reinforced cell invasion and c‐Myc expression. In addition, the transformed cells formed progressively growing tumors upon inoculation into athymic nude mice. Specifically, α‐irradiation induced damage to both mitochondrial DNA (mtDNA) and mitochondrial functions in transformed cells as evidenced by increased mtDNA copy number and common deletion, decreased oxidative phosphorylation activity as measured by cytochrome C oxidase (COX) activity and oxygen consumption. There was a linear correlation between mtDNA copy number, common deletion, COX activity and cellular transformation represented by soft agar colony formation and c‐Myc expression. These results suggest that mitochondria are associated with neoplastic transformation of SAEC cells induced by α‐particles, and that the oncogenesis process may depend not only on the genomes inside the nucleus, but also on the mitochondrial DNA outside the nucleus.
Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70
Authors: Garbe Annette I , Roscher Anne , Schüler Christiane , Lutter Anne-Helen , Glösmann Martin , Bernhardt Ricardo , Chopin Michael , Hempel Ute , Hofbauer Lorenz C , Rammelt Stefan , Egerbacher Monika , Erben Reinhold G , Jessberger Rolf
Published: May 2012

Bone remodeling involves tightly regulated bone-resorbing osteoclasts and bone-forming osteoblasts. Determining osteoclast function is central to understanding bone diseases such as osteoporosis and osteopetrosis. Here, we report a novel function of the F-actin binding and regulatory protein SWAP-70 in osteoclast biology. F-actin ring formation, cell morphology, and bone resorption are impaired in Swap-70−/− osteoclasts, whereas the expression of osteoclast differentiation markers induced in vitro by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) remains unaffected. Swap-70−/− mice develop osteopetrosis with increased bone mass, abnormally dense bone, and impaired osteoclast function. Ectopic expression of SWAP-70 in Swap-70−/− osteoclasts in vitro rescues their deficiencies in bone resorption and F-actin ring formation. Rescue requires a functional pleckstrin homology (PH) domain, known to support membrane localization of SWAP-70, and the F-actin binding domain. Transplantation of SWAP-70–proficient bone marrow into Swap-70−/− mice restores osteoclast resorption capacity in vivo. The identification of the role of SWAP-70 in promoting osteoclast function through modulating membrane-proximal F-actin rearrangements reveals a new pathway to control osteoclasts and bone homeostasis. © 2012 American Society for Bone and Mineral Research.
Thrombotic thrombocytopenic purpura precipitated by thyrotoxicosis
Authors: Chhabra Saurabh , Tenorio Grace
Published: May 2012

Thrombotic thrombocytopenic purpura (TTP) may be seen in association with autoimmune disorders such as immune hemolytic anemia and systemic lupus erythematosus, but rarely has it been associated with Graves' disease. We report one such case of a woman with new‐onset thyrotoxicosis caused by Graves' disease, who abruptly developed TTP, confirmed by low serum ADAMTS‐13 value. She had a dramatic response to plasma exchange, with remission of TTP. Definitive treatment with radioactive iodine resulted in euthyroidism and has prevented recurrence of TTP. J. Clin. Apheresis 27:265–266, 2012. © 2012 Wiley Periodicals, Inc.
Reoptimized interaction parameters for the peptide‐backbone model compound N‐methylacetamide in the GROMOS force field: Influence on the folding properties of two beta‐peptides in methanol
Authors: Horta Bruno A. C. , Lin Zhixiong , Huang Wei , Riniker Sereina , van Gunsteren Wilfred F. , Hünenberger Philippe H.
Published: May 2012

Considering N‐methylacetamide (NMA) as a model compound, new interaction parameters are developed for the amide function in the GROMOS force field that are compatible with the recently derived 53A6OXY parameter set for oxygen‐containing chemical functions. The resulting set, referred to as 53A6OXY+A, represents an improvement over earlier GROMOS force‐field versions in the context of the pure‐liquid properties of NMA, including the density, heat of vaporization, dielectric permittivity, self‐diffusion constant and viscosity, as well as in terms of the Gibbs hydration free energy of this molecule. Assuming that NMA represents an adequate model compound for the backbone of peptides, 53A6OXY+A may be expected to also provide an improved description of polypeptide chains. As an initial test, simulations are reported for two β‐peptides characterized by very different folding properties in methanol. For these systems, earlier force‐field versions provided good agreement with experimental NMR data, and the test shows that the improved description achieved in the context of NMA is not accompanied by any deterioration in the representation of the conformational properties of these peptides. © 2012 Wiley Periodicals, Inc.
The Generation of Variation and the Developmental Basis for Evolutionary Novelty
Authors: HALLGRÍMSSON BENEDIKT , JAMNICZKY HEATHER A. , YOUNG NATHAN M. , ROLIAN CAMPBELL , SCHMIDT‐OTT URS , MARCUCIO RALPH S.
Published: May 2012

Organisms exhibit an incredible diversity of form, a fact that makes the evolution of novelty seemingly self‐evident. However, despite the “obvious” case for novelty, defining this concept in evolutionary terms is highly problematic, so much so that some have suggested discarding it altogether. Approaches to this problem tend to take either an adaptation‐ or development‐based perspective, but we argue here that an exclusive focus on either of these misses the original intent of the novelty concept and undermines its practical utility. We propose instead that for a feature to be novel, it must have evolved both by a transition between adaptive peaks on the fitness landscape and that this transition must have overcome a previous developmental constraint. This definition focuses novelty on the explanation of apparently difficult or low‐probability evolutionary transitions and highlights how the integration of developmental and functional considerations are necessary to evolutionary explanation. It further reinforces that novelty is a central concern not just of evolutionary developmental biology (i.e., “evo‐devo”) but of evolutionary biology more generally. We explore this definition of novelty in light of four examples that range from the obvious to subtle. J. Exp. Zool. (Mol. Dev. Evol.) 318B:501–517, 2012. © 2012 Wiley Periodicals, Inc.
Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral‐mediated atrial natriuretic peptide delivery
Authors: Larifla Laurent , Déprez Isabelle , Pham Isabelle , Rideau Dominique , Louzier Vanessa , Adam Micheline , Eloit Marc , Foucan Lydia , Adnot Serge , Teiger Emmanuel
Published: May 2012

Background

Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury.

Methods

ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad‐RSV‐ANP). A recombinant adenovirus expressing the RSV‐controlled β‐galactosidase gene (Ad‐RSV‐β‐gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution.

Results

VSMCs transfected by Ad‐RSV‐ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad‐RSV‐ANP‐treated group compared to the control group.

Conclusions

The present study demonstrates the efficacy of recombinant adenovirus Ad‐RSV‐ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of nontechnical leadership practices on it project success
Authors: Kaminsky Jason B.
Published: May 2012

This article examines the leadership practices utilized by information technology (IT) project managers that contribute to project success. Specifically, technical and nontechnical leadership practices are contrasted. The importance of nontechnical leadership practices in IT project management has been largely ignored in research until recently. The article identifies key nontechnical leadership practices that are important for the success of IT projects. The article is based on a qualitative study that gathered data from actual IT projects conducted at U.S. companies across several different industry segments. Study results are analyzed to determine the relevance and value of Heifetz's adaptive leadership framework to the area of IT project management. Study findings indicate that nontechnical leadership practices are important to the success of IT projects. Findings also indicate that Heifetz's adaptive leadership framework is consistent with the key nontechnical leadership practices that are important for the success of IT projects. A framework for the development of IT project managers is also proposed.
The intercultural communication cultural immersion experience: Preparing leaders for a global future
Authors: Caputo John S. , Crandall Heather M.
Published: May 2012

The dynamics of globalization mean we face a reality wherein leaders are called upon to communicate effectively in cultural situations unfamiliar to them. This situation brings new challenges for communication and leadership educators. Our article describes a cultural immersion experience called The Cagli Project, where communication and leadership students learn effective intercultural communication skills for leadership formation while studying in Italy. The philosophical and experiential aspects of the program are described along with leadership outcomes. The article ends with a discussion of the transferability of this model to alternative programs.

Perhaps nothing has had a more profound effect on human communication and hence leadership in the past half century than the movement of people around the globe and the growing diversity of world society. Globalization is the mantra that seems to be driving much that is new in higher education today. It has its roots in the “global economy” and seems most relevant to the business disciplines, but there is a sub‐text to globalization that resonates throughout all our institutions, and that is diversity (Caputo, 2011).
Learning about hardiness and servant leadership by accompanying refugees at a united nations resettlement camp
Authors: Popa Adrian B.
Published: May 2012

The internationalization of curriculum has contributed to a number of models for study abroad programs, service learning, and global engagement. Some frameworks are intentionally grounded in program theories and objectives shared by multiple stakeholders and the mission of the sponsoring academic institution. This article describes an international program inspired by a partnership between a Jesuit University and the United Nations agency charged with the purpose of safeguarding the rights and well‐being of refugees. The international program was grounded in the practice of accompaniment and theoretical frameworks of hardiness and servant leadership. These principles are described in the context of the curriculum, objectives, activities, and outcomes. The article concludes with lessons learned and future direction for design and delivery.
Evolutionary leadership theory
Authors: Kenney Matthew T.
Published: May 2012

This article reviews an important new monograph on evolutionary leadership theory by Mark van Vugt and Anjana Ahuja (Naturally Selected: The Evolutionary Science of Leadership. New York: HarperBusiness, 2011, 272 pp. ISBN 978‐0‐06196‐383‐4, $25.99, Hardcover). I summarize the main arguments of this work, which draws on evolutionary psychology and Charles Darwin's theory of natural selection to explain why and under what circumstances leadership and followership traits emerged in human societies. In so doing, I assess the extent to which it succeeds, as intended, in providing a scientifically rigorous framework for our understanding of leadership in the 21st century.
Significance of the “Delayed hyperintense portal vein sign” in the hepatobiliary phase MRI obtained with Gd‐EOB‐DTPA
Authors: Lee Nam Kyung , Kim Suk , Kim Gwang Ha , Heo Jeong , Seo Hyung Il , Kim Tae Un , Kang Dae Hwan
Published: May 2012

Purpose:

To determine the significance of the delayed hyperintense portal vein sign in Gd‐EOB‐DTPA‐enhanced magnetic resonance imaging (MRI).

Materials and Methods:

This retrospective study was approved by the Institutional Review Board and the requirement for informed patient consent was obtained. Six‐hundred and seventy patients who underwent Gd‐EOB‐DTPA‐enhanced MRI were included in the study. Two readers who were blinded to clinical records reviewed MR images in consensus. The delayed hyperintense portal vein sign was defined if the portal vein appeared more hyperintense than surrounding liver parenchyma on the 30‐minute delayed hepatobiliary phase. The frequency of the delayed hyperintense portal vein sign and the association between the sign and serum biochemical tests were assessed. Multivariate analysis was performed to identify which variables were associated with the sign. Optimal cutoff values of variables for reflecting the sign were obtained with ROC analysis.

Results:

The delayed hyperintense portal vein sign was observed in 13.0%. In multivariate analysis, a direct bilirubin level was associated with the delayed hyperintense portal vein sign. Optimum cutoff value for reflecting the delayed hyperintense portal vein sign was 2.18 mg/dL (sensitivity, 89%; specificity, 96%).

Conclusion:

The delayed hyperintense portal vein sign in Gd‐EOB‐DTPA‐enhanced MRI can potentially be used to reflect hepatobiliary function. J. Magn. Reson. Imaging 2012;36:678–685. © 2012 Wiley Periodicals, Inc.
Signal polarity restoration in a 3D inversion recovery sequence used with delayed gadolinium‐enhanced magnetic resonance imaging of cartilage (dGEMRIC)
Authors: Szumowski Jerzy , Durkan Michael G. , Foss Erik W. , Brown Dawson S. , Schwarz Erwin , Crawford Dennis C.
Published: May 2012

Purpose:

To develop an image reconstruction algorithm that restores the signal polarity in a three‐dimensional inversion‐recovery (3D‐IR) sequence used in delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC). This approach effectively doubles the dynamic range of data used for T1 curve fitting.

Materials and Methods:

We applied this reconstruction algorithm to a 3D‐IR TFE sequence used for T1 mapping, validated the technique in a phantom study, and performed T1‐map calculations in postosteochondral allograft transplant (OAT) patients. In addition, we performed a signal simulation study to assess the algorithm's capability to reduce the number of inversion times used in the 3D‐IR TFE sequence.

Results:

In comparison to a standard T1‐mapping algorithm that uses the magnitude of the MRI signal, the proposed algorithm improves the reliability of T1 relaxation fits to the inversion‐recovery three‐parameter function. The signal simulation study shows that the number of TI inversion times can be reduced to as few as four, without compromising the accuracy of T1 calculations.

Conclusion:

This algorithm can be applied to any 2D‐ or 3D‐IR acquisition sequence used in conjunction with dGEMRIC. Application of the algorithm improves the reliability of T1 calculations and allows the number of TIs to be reduced, leading to shorter scan times in dGEMRIC. J. Magn. Reson. Imaging 2012;36:1248–1255. © 2012 Wiley Periodicals, Inc.
Observer reactions to interpersonal injustice: The roles of perpetrator intent and victim perception
Authors: Umphress Elizabeth E. , Simmons Aneika L. , Folger Robert , Ren Run , Bobocel Ramona
Published: May 2012

The present research contributes to a growing literature on observer reactions to injustice experienced by others. In particular, we separated two variables that have previously been confounded in prior research, namely perpetrator intent to cause harm and victim perception of harm. We expected that injustice intent and injustice perceptions would have both unique and joint effects on observer reactions. The results of three experiments in which we manipulated perpetrator injustice intent and victim injustice perceptions supported our predictions. First, we found that observers had more negative reactions toward superiors who intended to inflict high versus low levels of interpersonal injustice toward a subordinate. Second, the injustice intent of the superior influenced observers' reactions more than did victim perceptions of injustice. Third, most novel, we found that the mere intent to cause injustice generated negative reactions in observers, even in the absence of a “true” victim—that is, when the subordinate perceptions of injustice were low. Together, our results emphasize the importance of examining observers' reactions to injustice and incorporating perpetrator intentions into the study of organizational justice. Copyright © 2012 John Wiley & Sons, Ltd.
Bias correction of daily precipitation simulated by a regional climate model: a comparison of methods
Authors: Lafon Thomas , Dadson Simon , Buys Gwen , Prudhomme Christel
Published: May 2012

Quantifying the effects of future changes in the frequency of precipitation extremes is a key challenge in assessing the vulnerability of hydrological systems to climate change but is difficult as climate models do not always accurately simulate daily precipitation. This article compares the performance of four published techniques used to reduce the bias in a regional climate model precipitation output: (1) linear, (2) nonlinear, (3) γ‐based quantile mapping and (4) empirical quantile mapping. Overall performance and sensitivity to the choice of calibration period were tested by calculating the errors in the first four statistical moments of generated daily precipitation time series and using a cross‐validation technique. The study compared the 1961–2005 precipitation time series from the regional climate model HadRM3.0‐PPE‐UK (unperturbed version) with gridded daily precipitation time series derived from rain gauges for seven catchments spread throughout Great Britain. We found that while the first and second moments of the precipitation frequency distribution can be corrected robustly, correction of the third and fourth moments of the distribution is much more sensitive to the choice of bias correction procedure and to the selection of a particular calibration period. Overall, our results demonstrate that, if both precipitation data sets can be approximated by a γ‐distribution, the γ‐based quantile‐mapping technique offers the best combination of accuracy and robustness. In circumstances where precipitation data sets cannot adequately be approximated using a γ‐distribution, the nonlinear method is more effective at reducing the bias, but the linear method is least sensitive to the choice of calibration period. The empirical quantile mapping method can be highly accurate, but results were very sensitive to the choice of calibration time period. However, it should be borne in mind that bias correction introduces additional uncertainties, which are greater for higher order moments. Copyright © 2012 Royal Meteorological Society
A method to estimate sky view factors from digital elevation models
Authors: Kastendeuch Pierre P.
Published: May 2012

Sky view factor (SVF) is a commonly used parameter in atmospheric sciences. A method how to obtain an approximate value of SVF from digital elevation models (DEM) is described. The method takes into account slopes and transmittance of objects and is able to compute SVF for complex geometries (e.g. urban environments, natural landscapes, etc.). It is based on the concept of view factor, sometimes called ‘form factor’ or ‘shape factor’ in the literature. The view factors are computed between the calculation point and numeric sky dome to obtain an estimate of the final SVF value. A special procedure is applied to take limitation of sky visibility by obstacles into account. Accuracy of the method is checked by comparison with theoretical SVF values and tested on examples of complex geometries. Copyright © 2012 Royal Meteorological Society
Conformity and precision of CO2 densimetry in CO2 inclusions: microthermometry versus Raman microspectroscopic densimetry
Authors: Kobayashi Tomoyuki , Yamamoto Junji , Hirajima Takao , Ishibashi Hidemi , Hirano Naoto , Lai Yong , Prikhod'ko Vladimir S. , Arai Shoji
Published: May 2012

To assess the ability of densimetry for CO2 fluid in CO2 inclusions, we compare two methods, microthermometry and Raman microspectroscopic densimetry for CO2. The comparative experiment was performed for nine CO2 inclusions in three mantle xenoliths. The results are as follows: (1) microthermometry precisely determines CO2 density with the range of 0.65 to 1.18 g/cm3 compared with Raman microspectroscopic densimetry; (2) CO2 density obtained by Raman microspectroscopic densimetry is fairly consistent with that by microthermometry; (3) it is hard to determine CO2 density in CO2 inclusion with diameter of less than around 3 µm using microthermometry; and (4) microthermometry can be applied only to the CO2 inclusion whose CO2 density ranges from around 0.65 to 1.18 g/cm3, whereas the Raman microspectroscopic densimetry is applicable to CO2 density ranging from 0.1 to 1.24 g/cm3. The above features carry the potential for estimation of depth origin of mantle‐derived rocks. The depth where the rocks were trapped by host magma can be estimated using both geothermometric data and CO2 fluid density in CO2 inclusions in the rocks. Typical precisions of density of CO2 in CO2 inclusions obtained by the Raman microspectroscopic densimetry (~0.01 g/cm3) and by the microthermometry (< 0.001 g/cm3) correspond to uncertainties in the depth origin of 2.4 km and < 1.7 km, respectively, at 1000 ± 50 °C. In case of the mantle under 750–1250 °C and 1 GPa, the CO2 fluid has a density ranging from 1.06 g/cm3 to 1.21 g/cm3, which are well measured by the Raman microspectroscopic densimetry. Combination of both densimetries for CO2 in mantle minerals elucidates the deep structure of the Earth. Copyright © 2012 John Wiley & Sons, Ltd.
Hereditary pheochromocytoma and paraganglioma
Authors: Mazzaglia Peter J.
Published: May 2012

Hereditary pheochromocytomas (pheo) and paragangliomas (pgl) are caused by identifiable germline mutations. The previously well‐known associated syndromes include neurofibromatosis type 1, multiple endocrine neoplasia 2 A and B, and von Hippel‐Lindau syndrome. Newly discovered mutations in the succinate dehydrogenase gene complex have been identified as a cause of inherited pgls and pheos. It is now clear that up to 30% of patients presenting with sporadic pheos/pgls harbor a recognizable germline mutation, and therefore directed genetic testing is recommended for many of these patients. J. Surg. Oncol. 2012; 106:580–585. © 2012 Wiley Periodicals, Inc.
Summary outcomes of two‐stage resection for advanced colorectal liver metastases
Authors: Chua Terence C. , Liauw Winston , Chu Francis , Morris David L.
Published: May 2012

Background

Surgical resection is associated with improved long‐term survival in patients with colorectal liver metastases (CLM). However, majority of patients have unresectable bilobar advanced liver metastases. Two‐stage resection (TSR) allows selected patients to achieve complete resection when combined with chemotherapy and interventional radiological procedures.

Methods

Electronic search of the MEDLINE and PubMed databases (January 2000–October 2011) to identify studies examining the outcomes of the surgical approach of TSR of advanced CLM was undertaken.

Results

Twelve studies were examined. This comprised 488 patients. A median of 77% (range: 64–100%) of planned patients completed TSR. The most common reason for failure was due to disease progression observed in a median of 100% (range: 56–100%) of patients. Second‐stage resection appeared to be more morbid compared to first‐stage resection with higher complication rates (33% vs. 14%) and requiring more blood transfusions (3 U vs. 1 U). Completed TSR achieved a median survival of 37 (range: 18–66) months, median 3‐year survival rate of 60% (range: 45–84%), and median 5‐year survival rate of 48% (range: 32–70%). In patients who failed TSR, the median survival was 16 (range: 10–29) months.

Conclusion

In carefully selected candidates with advanced bilobar CLM, the TSR approach achieves long‐term survival in patients who would otherwise be considered for palliative chemotherapy only. Despite failing to complete TSR, patients had an encouraging survival outcome that appeared to compare favorably over palliative chemotherapy alone. J. Surg. Oncol. 2013;107:211–216. © 2012 Wiley Periodicals, Inc.
Circulating miR‐34a levels are reduced in colorectal cancer
Authors: Nugent M. , Miller N. , Kerin M.J.
Published: May 2012

Introduction

MicroRNAs (miRNAs) are small, non‐coding RNA segments that regulate gene expression via post‐transcriptional inhibition and have roles in cell differentiation, proliferation, and apoptosis. Expression differs between tumor and normal tissue in several malignancies. Most work has focused on tissue and cell expression with few reports of circulating miRNAs in colorectal cancer. Available biomarkers for colorectal cancer have limited sensitivity and specificity, thus there is a need for new markers.

Aims

This study aimed to identify miRNAs that are differentially expressed in the blood of colorectal cancer patients compared to controls and to establish if this is specific to colorectal cancer and thus could be utilized as potential tumor markers.

Methods

Blood samples were collected from 63 colorectal cancer patients and 45 controls. Expression of 7 target miRNAs (miR‐143, miR‐145, miR‐21, miR‐30a‐3p, miR‐31, miR‐34a, and miR‐92) was measured using RQ‐PCR. Results were correlated with clinicopathological data and analyzed. Analysis of differentially expressed circulating miRNAs was expanded to include 62 patients with prostate, renal, breast, and melanoma cancers.

Results

Analysis of the relative quantification of the target miRNAs showed significantly reduced expression (P = 0.004) of miR‐34a in colorectal cancer. MiR‐34a was also significantly reduced in breast cancer (P = 0.019).

Conclusion

This study demonstrates significantly reduced expression of circulating miR‐34a in colorectal and breast cancer. This may have future application as part of a biomarker profile. J. Surg. Oncol. 2012; 106: 947–952. © 2012 Wiley Periodicals, Inc.
Intervention effectiveness among war‐affected children: A cluster randomized controlled trial on improving mental health
Authors: Qouta Samir R. , Palosaari Esa , Diab Marwan , Punamäki Raija‐Leena
Published: May 2012

We examined the effectiveness of a psychosocial intervention in reducing mental health symptoms among war‐affected children, and the role of peritraumatic dissociation in moderating the intervention impact on posttraumatic stress symptoms (PTSS). School classes were randomized into intervention (n = 242) and waitlist control (n = 240) conditions in Gaza, Palestine. The intervention group participated in 16 extracurriculum sessions of teaching recovery techniques (TRT) and the controls received normal school‐provided support. Participants were 10‐ to 13‐year‐old Palestinian girls (49.4%) and boys (50.6%). Data on PTSS, depressive symptoms, and psychological distress were collected at baseline (T1), postintervention (T2), and 6‐month follow‐up (T3). Peritraumatic dissociation was assessed only at baseline. Regression analyses that took regression to the mean and cluster sampling into account were applied. The results on intervention effectiveness were specific to gender and peritraumatic dissociation. At T2, the intervention significantly reduced the proportion of clinical PTSS among boys, and both the symptom level (R2 = .24), and proportion of clinical PTSS among girls who had a low level of peritraumatic dissociation. The results have implications for risk‐specific tailoring of psychosocial interventions in war conditions.
Poly(ethylene carbonate) Nanoparticles as Carrier System for Chemotherapy Showing Prolonged in vivo Circulation and Anti‐Tumor Efficacy
Authors: Renette Thomas , Librizzi Damiano , Endres Thomas , Merkel Olivia , Beck‐Broichsitter Moritz , Bege Nadja , Petersen Holger , Curdy Catherine , Kissel Thomas
Published: May 2012

The aim of this study is to investigate the feasibility and efficacy of PEC nanoparticles as delivery system for cancer chemotherapy. Assembly of paclitaxel‐loaded nanoparticles with high loading efficiency and narrow‐size distribution is successful. For non‐invasive in vivo tracing, nanoparticle blends of chelator bearing poly(lactide) with PEC and PLGA are successfully prepared. Pharmacokinetic studies in mice reveal a twofold higher circulation time of PEC as compared to PLGA. A tumor model shows an accumulation of PEC NPs in cancerous tissue and a higher anti‐tumor efficiency compared to the standard Taxol™, which is reflected in a significantly slower tumor growth compared to the NaCl control group.

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Poly(2‐ethyl‐2‐oxazoline) as Alternative for the Stealth Polymer Poly(ethylene glycol): Comparison of in vitro Cytotoxicity and Hemocompatibility
Authors: Bauer Marius , Lautenschlaeger Christian , Kempe Kristian , Tauhardt Lutz , Schubert Ulrich S. , Fischer Dagmar
Published: May 2012

Limitations of PEG in drug delivery have been reported from clinical trials. PEtOx (0.4–40 kDa) as alternative is synthesized by a living, microwave‐assisted polymerization, and is directly compared to PEG of similar molar mass regarding cytotoxicity and hemocompatibility. In short‐term treatments, both types of polymers are well tolerated even at high concentrations. Moderate concentration and molar mass dependent cytotoxic effects occurred only after long‐term incubation at concentrations higher than therapeutic doses. PEtOx possesses not only an easy route of synthesis and beneficial physicochemical characteristics such as low viscosity and high stability, which are advantageous over PEG, but additionally in vitro toxicology comparable to PEG.

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Magnetic resonance imaging of the substantia nigra in Parkinson's disease
Authors: Lehéricy Stéphane , Sharman Michael A. , Santos Clarisse Longo Dos , Paquin Raphaël , Gallea Cecile
Published: May 2012

Until recently, conventional magnetic resonance imaging (MRI) was most often negative in Parkinson's disease or showed nonspecific findings. Recent developments in structural MRI, including relaxometry, magnetization transfer, and neuromelanin imaging, have demonstrated improved contrast and enabled more accurate visualization of deep brain nuclei, in particular, the substantia nigra. Meanwhile, diffusion imaging has provided useful biomarkers of substantia nigra degeneration, showing reduced anisotropy and anatomical connectivity with the striatum and thalamus. These advances in structural imaging are complemented by findings of magnetic resonance spectroscopy on brain metabolism and resting‐state functional MRI on functional connectivity. This article presents an overview of these new structural, metabolic, and resting‐state functional MRI techniques and their implications for Parkinson's disease. The techniques are reviewed in the context of their potential for better understanding the disease in terms of diagnosis and pathophysiology and as biomarkers of its progression. © 2012 Movement Disorder Society
Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease
Authors: Walker Harrison C. , Huang He , Gonzalez Christopher L. , Bryant James E. , Killen Jeffrey , Cutter Gary R. , Knowlton Robert C. , Montgomery Erwin B. , Guthrie Bart L. , Watts Ray L.
Published: May 2012

Subthalamic deep brain stimulation (DBS) is superior to medical therapy for the motor symptoms of advanced Parkinson's disease (PD), and additional evidence suggests that it improves refractory symptoms of essential tremor, primary generalized dystonia, and obsessive‐compulsive disorder. Despite this, its therapeutic mechanism is unknown. We hypothesized that subthalamic stimulation activates the cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for PD. In 5 subjects (six hemispheres), EEG measured the response of cortex to subthalamic stimulation across a range of stimulation voltages and frequencies. Novel analytical techniques reversed the anode and cathode electrode contacts and summed the resulting pair of event‐related potentials to suppress the stimulation artifact. We found that subthalamic brain stimulation at 20 Hz activates the somatosensory cortex at discrete latencies (mean latencies: 1.0 ± 0.4, 5.7 ± 1.1, and 22.2 ± 1.8 ms, denoted as R1, R2, and R3, respectively). The amplitude of the short latency peak (R1) during clinically effective high‐frequency stimulation is nonlinearly dependent on stimulation voltage (P < 0.001; repeated‐measures analysis of variance), and its latency is less variable than that of R3 (1.02 versus 19.46 ms; P < 0.001, Levene's test). We conclude that clinically effective subthalamic brain stimulation in humans with PD activates the cerebral cortex at 1 ms after stimulus onset, most likely by antidromic activation. These findings suggest that alteration of the precise timing of action potentials in cortical neurons with axonal projections to the subthalamic region may be an important component of the therapeutic mechanism of subthalamic brain stimulation. © 2012 Movement Disorder Society
Existence results for a class of semilinear nonlocal evolution equations
Authors: Liu Qing
Published: May 2012

In this paper, we study a class of semilinear evolution equations with nonlocal initial conditions and give some new results on the existence of mild solutions. Copyright © 2012 John Wiley & Sons, Ltd.
On a Sturm–Liouville type problem with retarded argument
Authors: Bayramov Azad , Şen Erdoğan
Published: May 2012

In this work, a Sturm–Liouville‐type problem with retarded argument, which contains spectral parameter in the boundary conditions and with transmission conditions at the point of discontinuity are investigated. We obtained asymptotic formulas for the eigenvalues and eigenfunctions. Copyright © 2012 John Wiley & Sons, Ltd.
Dietary intake of rosmarinic acid by ApcMin mice, a model of colorectal carcinogenesis: levels of parent agent in the target tissue and effect on adenoma development
Authors: Karmokar Ankur , Marczylo Timothy H. , Cai Hong , Steward William P. , Gescher Andreas J. , Brown Karen
Published: May 2012

Scope

Rosmarinic acid (RA), a constituent of culinary herbs is considered to possess cancer chemopreventive properties. It has been shown to inhibit the development of cancer in preclinical models but data are conflicting and whether it can protect against gastrointestinal malignancies in vivo has not been examined. This study aimed to investigate the effect of RA on the development of intestinal adenomas in the ApcMin mouse model of colorectal carcinogenesis, and to correlate efficacy with levels of RA achieved in the plasma and gastrointestinal tract.

Methods and results

RA inhibited the growth of APC10.1 cells derived from ApcMin mouse adenomas, with an IC50 of 43 μM. Consumption of dietary RA (0.3%) by ApcMin mice for 8 weeks post weaning decreased adenoma burden by ∼35%, but the difference from controls was not significant. Although RA significantly decreased the frequency of large adenomas, the number of small ones increased. Using a novel validated HPLC assay, average levels of RA in the plasma and intestinal mucosa of these mice were found to be 1.1 μM and 38 nmol/g, respectively.

Conclusion

Chronic consumption of RA furnished quantifiable levels of parent compound in the plasma and intestinal tract of ApcMin mice and may slow adenoma development.
Calcium‐sensing receptor mediates dietary peptide‐induced CCK secretion in enteroendocrine STC‐1 cells
Authors: Nakajima Shingo , Hira Tohru , Hara Hiroshi
Published: May 2012

Scope

Dietary peptides are potent stimulators of cholecystokinin (CCK) secretion, but the sensing mechanism in CCK‐producing cells is poorly understood. Recently, it has been demonstrated that the calcium‐sensing receptor (CaSR) mediates CCK secretion induced by amino acids. We investigated the role of CaSR in CCK secretions induced by various protein hydrolysates (egg albumin, meat, casein, azuki bean, soybean ß‐conglycinin, and potato) in the enteroendocrine cell line STC‐1.

Methods and results

CCK secretions in response to these hydrolysates were measured in the STC‐1 cells with or without CaSR antagonist (NPS 2143) treatment. Changes in intracellular calcium concentration ([Ca2+]i) in response to protein hydrolysates were measured in Human embryonic kidney (HEK) 293 cells transfected with CaSR‐expression vector. Protein hydrolysates‐induced CCK secretions were decreased by CaSR antagonist treatment, except meat hydrolysate‐induced secretion. Protein hydrolysates increased [Ca2+]i in CaSR‐transfected HEK 293 cells. CaSR antagonist treatment suppressed low molecular weight fractions of azuki hydrolysate‐induced CCK secretion, but the secretion induced by both low and high molecular weight fractions of ß‐conglycinin hydrolysate. Further, CCK secretion induced by peptide fractions (>500 Da) derived from various protein hydrolysates were also reduced by CaSR antagonist.

Conclusion

These results demonstrate that CaSR plays a significant role in sensing various dietary peptides in triggering CCK secretion in enteroendocrine cells.
Lycopene induces retinoic acid receptor transcriptional activation in mice
Authors: Aydemir Gamze , Carlsen Harald , Blomhoff Rune , Rühl Ralph
Published: May 2012

Scope

Lycopene is a lipophilic carotenoid and provides the red colour to tomatoes and tomato product. Various studies indicated that lycopene and tomatoes/tomato products are able to positively influence various diseases associated with a chronic inflammation. The mechanism of action of lycopene to elicit these effects is partly unknown. A possible mechanism is that biological metabolites of lycopene may activate nuclear hormone receptors in mammalian cells. The aim of this study was to investigate the potential of orally administered lycopene and all‐trans retinoic acid (ATRA) for the induction of the retinoic acid receptor (RAR) in a transgenic retinoic acid response‐element (RARE)‐reporter mouse system.

Methods and results

Orally administered lycopene (100 mg/kg bw in beadlets, n = 6) and ATRA as an endogenous RAR ligand (50 mg/kg bw, n = 6) for the induction of the retinoic acid receptor in male mice using a transgenic RARE‐reporter mouse system.

Conclusion

Lycopene treatments induced RARE‐mediated cell signalling indicated by quantified bioimaging, increased luciferase activity and up‐regulated the retinoid target genes in selected organs of the mice. We conclude that lycopene can induce RAR‐transcriptional activation in mice and lycopene might be a precursor of still non‐identified biologically active metabolites.
Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer‐binding protein β activation
Authors: Han Eun Hee , Kim Hyung Gyun , Choi Jae Ho , Jang Yin‐Jin , Lee Sang Seop , Kwon Kwang‐il , Kim Eunyoung , Noh Kyeumhan , Jeong Tae Cheon , Hwang Yong Pil , Chung Young Chul , Kang Wonku , Jeong Hye Gwang
Published: May 2012

Scope

Capsaicin (8‐methyl‐N‐vanillyl‐6‐nonenamide) is the principal pungent ingredient in hot red and chili peppers. Many studies have focused on the anticarcinogenic or chemopreventive activities of capsaicin. However, the influence of capsaicin on CYP3A4, its involvement in drug metabolism, and the underlying mechanisms remain unclear.

Methods and results

Here, we examined the effect of capsaicin on CYP3A4 expression and the metabolism of CYP3A1 substrate, nifedipine in male Sprague–Dawley rats. Capsaicin induced the enzymatic activity and expression of CYP3A4 in HepG2 cells. Treatment with a human pregnane X receptor (hPXR) inhibitor reduced the inductive effects of capsaicin on CYP3A4 expression. Capsaicin also induced the activation of CCAAT/enhancer‐binding protein β (C/EBPβ). Moreover, capsaicin increased the activation of the transient receptor potential vanilloid type‐1 receptor downstream signaling components Ca2+/calmodulin‐dependent protein kinase and Akt. Capsaicin elevated the level of CYP3A1 in rat liver and significantly increased the biotransformation of nifedipine to dehydronifedipine.

Conclusion

From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBPβ. Our results suggest that capsaicin might induce CYP3A4 expression; thus, exposure to capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause food–drug interactions.
Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis
Authors: Zhao Jing‐Feng , Ching Li‐Chieh , Huang Yu‐Chu , Chen Chien‐Yu , Chiang An‐Na , Kou Yu Ru , Shyue Song‐Kun , Lee Tzong‐Shyuan
Published: May 2012

Scope

Curcumin, a potent antioxidant extracted from Curcuma longa, confers protection against atherosclerosis, yet the detailed mechanisms are not fully understood. In this study, we examined the effect of curcumin on lipid accumulation and the underlying molecular mechanisms in macrophages and apolipoprotein E‐deficient (apoE−/−) mice.

Methods and results

Treatment with curcumin markedly ameliorated oxidized low‐density lipoprotein (oxLDL)‐induced cholesterol accumulation in macrophages, which was due to decreased oxLDL uptake and increased cholesterol efflux. In addition, curcumin decreased the protein expression of scavenger receptor class A (SR‐A) but increased that of ATP‐binding cassette transporter (ABC) A1 and had no effect on the protein expression of CD36, class B receptor type I (SR‐BI), or ATP‐binding cassette transporter G1 (ABCG1). The downregulation of SR‐A by curcumin was via ubiquitin–proteasome–calpain‐mediated proteolysis. Furthermore, the curcumin‐induced upregulation of ABCA1 was mainly through calmodulin‐liver X receptor α (LXRα)‐dependent transcriptional regulation. Curcumin administration modulated the expression of SR‐A, ABCA1, ABCG1, and SR‐BI in aortas and retarded atherosclerosis in apoE−/− mice.

Conclusion

Our findings suggest that inhibition of SR‐A‐mediated oxLDL uptake and promotion of ABCA1‐dependent cholesterol efflux are two crucial events in suppression of cholesterol accumulation by curcumin in the transformation of macrophage foam cells.