bluuebunny/crossref_metadata_2025 huggingface dataset:
Do learning approaches of medical students affect their satisfaction with problem-based learning?
Authors: Gurpinar Erol , Kulac Esin , Tetik Cihat , Akdogan Ilgaz , Mamakli Sumer
Published: March 2013

The aim of this research was to determine the satisfaction of medical students with problem-based learning (PBL) and their approaches to learning to investigate the effect of learning approaches on their levels of satisfaction. The study group was composed of medical students from three different universities, which apply PBL at different levels in their curricula. The revised two-factor study process survey was applied to the study group to determine their approaches to learning as “deep” or “surface” learning. In addition, another survey of 20 questions was used to determine satisfaction levels of students with PBL and other variables. Of the study group, 64.6% were found to adopt a deep approach to learning, and we confirmed that these students were reasonably more satisfied with PBL.
miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation
Authors: Fang Yi , Yu Xiaofang , Liu Yong , Kriegel Alison J. , Heng Yanyan , Xu Xialian , Liang Mingyu , Ding Xiaoqiang
Published: March 2013

Treatment with l-mimosine, which activates hypoxia-inducible factor-α (HIF-α), attenuates renal tubulointerstitial injury and improves renal function in a rat remnant kidney model. The miR-29 family of microRNAs directly targets a large number of extracellular matrix genes and reduces renal interstitial fibrosis. We analyzed microRNA expression profiles in rat remnant kidneys with or without treatment with l-mimosine. The expression of miR-29c was downregulated in rat remnant kidneys compared with sham control and significantly restored by the l-mimosine treatment. In cultured human kidney epithelial HK2 cells, cobalt chloride activated HIF-α and upregulated miR-29c expression. The upregulation of miR-29c expression was significantly attenuated by knockdown of HIF-1α or HIF-2α. Downregulation of miR-29c was associated with significant increases in interstitial fibrosis, collagen type II α1 (COL2A1) protein, and tropomyosin 1α (TPM1) protein in rat remnant kidneys and in kidneys from IgA nephropathy patients. The increases in rat remnant kidneys were attenuated by the l-mimosine treatment. COL2A1 and TPM1 were confirmed to be new, direct targets of miR-29c. In conclusion, miR-29c, an antifibrotic microRNA, is upregulated by HIF-α activation. MiR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by activation of HIF-α that attenuates fibrosis.
HIV compromises integrity of the podocyte actin cytoskeleton through downregulation of the vitamin D receptor
Authors: Chandel Nirupama , Sharma Bipin , Husain Mohammad , Salhan Divya , Singh Tejinder , Rai Partab , Mathieson Peter W. , Saleem Moin A. , Malhotra Ashwani , Singhal Pravin C.
Published: March 2013

Alterations in the podocyte actin cytoskeleton have been implicated in the development of proteinuric kidney diseases. In the present study, we evaluated the effect of HIV on the podocyte actin cytoskeleton and the mechanism involved. We hypothesized that HIV may be compromising the actin cytoskeleton via downregulation of the vitamin D receptor (VDR) of conditionally immortalized differentiated human podocytes (CIDHPs). HIV-transduced podocytes (HIV/CIDHPs) not only displayed downregulation of VDR but also showed activation of the renin-angiotensin system (RAS) in the form of enhanced expression of renin and increased production of ANG II. Moreover, CIDHPs lacking VDR displayed enhanced ANG II production, and treatment of HIV/CIDHPs with EB1089 (vitamin D3; VD) attenuated ANG II production. HIV/CIDHPs as well as ANG II-treated CIDHPs exhibited enhanced expression of cathepsin (CTS) L. Additionally, losartan (an ANG II type I receptor blocker) inhibited both HIV- and ANG II-induced podocyte cathepsin L expression. Furthermore, VD downregulated HIV-induced podocyte CTSL expression. Both losartan and free radical scavengers attenuated HIV- and ANG II-induced podocyte reactive oxygen species (ROS) generation. HIV also led to cytosolic CTSL accumulation through enhancement of podocyte lysosomal membrane permeabilization; on the other hand, VD, losartan, and superoxide dismutase (SOD) attenuated HIV-induced enhanced podocyte cytosolic CTSL accumulation. Morphological evaluation of HIV/CIDHPs revealed sparse actin filaments and attenuated expression of dynamin. Interestingly, podocytes lacking CTSL displayed enhanced dynamin expression, and HIV/CIDHPs expressing CTSL exhibited downregulation of dynamin. These findings indicate that HIV-induced downregulation of podocyte VDR and associated RAS activation and cytosolic CTSL accumulation compromised the actin cytoskeleton.
The lateral intraparietal area codes the location of saccade targets and not the dimension of the saccades that will be made to acquire them
Authors: Steenrod Sara C. , Phillips Matthew H. , Goldberg Michael E.
Published: March 2013

Activity in the lateral intraparietal area (LIP) represents a priority map that can be used to direct attention and guide eye movements. However, it is not known whether this activity represents the location of saccade targets or the actual eye movement made to acquire them. We recorded single neurons from rhesus macaques ( Macaca mulatta) while they performed memory-guided delayed saccades to characterize the response profiles of LIP cells. We then separated the saccade target from the saccade end point by saccadic adaptation, a method that induces a change in the gain of the oculomotor system. We plotted LIP activity for all three epochs of the memory-guided delayed-response task (visual, delay period, and presaccadic responses) as a function of target location and saccade end point. We found that under saccadic adaptation the response profile for all three epochs was unchanged as a function of target location. We conclude that neurons in LIP reliably represent the locations of saccade targets, not the amplitude of the saccade required to acquire those targets. Although LIP transmits target information to the motor system, that information represents the location of the target and not the amplitude of the saccade that the monkey will make.
Hypofractionated External-Beam Radiotherapy for Prostate Cancer
Authors: Cho L. Chinsoo , Timmerman Robert , Kavanagh Brian
Published: March 2013

There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity.
Effects of ROI Placement on PET-Based Assessment of Tumor Response to Therapy
Authors: Sattarivand Mike , Caldwell Curtis , Poon Ian , Soliman Hany , Mah Katherine
Published: March 2013

Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). Commonly, a fixed-size ROI is placed at the maximum uptake point in the pretreatment study. For intratreatment, the ROI is placed either at the maximum uptake point (ROIpeak) or at the same location as the pretreatment ROI (ROIsame). We have evaluated the effects of the ROI placement on response assessment. Methods. PET scans of 15 head and neck cancer patients were used to evaluate the effects of the two ROI methods on response assessment. Results. The average intratreatment ROIpeak uptake was 13.4% higher than the ROIsame uptake (range −14% to 38%). The average relative change in ROIpeak uptake was 7.9% lower than ROIsame uptake (range −5% to 36%), resulting in ambiguous tumour classification in 19% of the tumours. Conclusion. Quantitative PET response assessment using a fixed-size ROI is sensitive the ROI placement. The difference between ROIpeak and ROIsame could be substantial resulting in ambiguous response assessment. Although the fixed-size ROI is simple to implement, it is also prone to the limitations and should be used with caution. Clinical trial data are necessary to establish reliable thresholds for fixed-size ROI techniques and to evaluate their efficacy for response assessment.
Convergence and Characterization of Wavelets Associated with Dilation Matrix in Variable Spaces
Authors: Kumar Devendra
Published: March 2013

We study the convergence of wavelet expansions associated with dilation matrix in the variable spaces using the approximate identity. Also, we obtain conditions for the wavelet characterizations of with respect to norm estimates. Moreover, the results of Izuki (2008) and Kumar (2009) have been extended.
Rare Giant Granular Cell Ameloblastoma: A Case Report and an Immunohistochemical Study
Authors: Hunasgi Santosh , Koneru Anila , Chauhan Dinesh Singh , Guruprasad Yadavalli
Published: March 2013

Aims. The aim is to present a case of rare giant granular cell ameloblastoma and to review the pertinent literature highlighting the molecular aspects of its pathogenesis by analyzing the expression of CD-68, Bcl-2, andβ-catenin.Methods. H and E stained sections showed large odontogenic islands showing peripheral ameloblast-like cells and central stellate reticulum-like cells with extensive granular cell transformation surrounded by fibrous stroma. Polyclonal rabbit anti-CD 68, anti-Bcl2, and anti-β-catenin were stained immunohistochemically.Results. CD-68 showed a moderate to strong staining intensity in granular cells. Moderate staining of Bcl-2 was expressed by the peripheral columnar cells of tumor islands and negative in the granular cells. Expression ofβ-catenin was generally weak, except for only the focal areas that showed a moderate staining intensity and weak in peripheral cells.Conclusion. The present case of giant granular cell ameloblastoma is a rare entity. Development of monstrous size is indicative of ameloblastomas persistent growth. Granular cell transformation in ameloblastomas probably occurs as a consequence of extensive molecular changes. Immunohistochemical studies help us to know the pathogenesis of this granular cell ameloblastoma. Therefore, an effort has been made here to study the expression of Bcl-2, CD-68, andβ-catenin.
Living with Uncertainty: Older Persons’ Lived Experience of Making Independent Decisions over Time
Authors: Breitholtz Agneta , Snellman Ingrid , Fagerberg Ingegerd
Published: March 2013

The aim of the study was to illuminate the meaning of older persons’ independent decision making concerning their daily care. Autonomy when in care is highly valued in the western world. However, research shows that autonomy can give rise to problematic issues. The complexity of independence and dependence for older people when living at home with help has also been highlighted. In Sweden, older people are increasingly expected to live at home with help from municipal home care services, and study into this aspect of care is limited. This study is a part of an ongoing project and has a qualitative life world perspective. Audiotaped narrative interviews were conducted and analysed using a phenomenological hermeneutic method. Findings revealed a main theme: “living with uncertainty as to how to relate one’s own independence and dependence with regard to oneself, and others.” This involves a constant process of relating to one’s independence controlled by others or oneself, and adjusting one’s independence and dependence with regard to oneself and others. The conclusion is that professional carers need to acknowledge the changing vulnerability of dependent older persons over time. The implication is a relational approach to autonomy beyond the traditional individualistic approach.
Increasing Membrane Cholesterol Level Increases the Amyloidogenic Peptide by Enhancing the Expression of Phospholipase C
Authors: Chun Yoon Sun , Oh Hyun Geun , Park Myoung Kyu , Kim Tae-Wan , Chung Sungkwon
Published: March 2013

Cerebral elevation of 42-residue amyloidβ-peptide (Aβ42) triggers neuronal dysfunction in Alzheimer's disease (AD). Even though a number of cholesterol modulating agents have been shown to affect Aβgeneration, the role of cholesterol in the pathogenesis of AD is not clear yet. Recently, we have shown that increased membrane cholesterol levels downregulates phosphatidylinositol 4,5-bisphosphate (PIP2) via activation of phospholipase C (PLC). In this study, we tested whether membrane cholesterol levels may affect the Aβ42 production via changing PIP2levels. Increasing membrane cholesterol levels decreased PIP2and increased secreted Aβ42. Supplying PIP2, by using a PIP2-carrier system, blocked the effect of cholesterol on Aβ42. We also found that cholesterol increased the expressions ofβ1 andβ3 PLC isoforms (PLCβ1, PLCβ3). Silencing the expression of PLCβ1 prevented the effects of cholesterol on PIP2levels as well as on Aβ42 production, suggesting that increased membrane cholesterol levels increased secreted Aβ42 by downregulating PIP2via enhancing the expression of PLCβ1. Thus, cholesterol metabolism may be linked to Aβ42 levels via PLCβ1 expression and subsequent changes in PIP2metabolism.
A Study on Ricci Solitons in Kenmotsu Manifolds
Authors: Bagewadi C. S. , Ingalahalli Gurupadavva , Ashoka S. R.
Published: March 2013

We study and obtain results on Ricci solitons in Kenmotsu manifolds satisfying , , , and , where and are C-Bochner and pseudo-projective curvature tensor.
Remote Sensing of Soil Moisture
Authors: Lakshmi Venkat
Published: March 2013

Soil moisture is an important variable in land surface hydrology as it controls the amount of water that infiltrates into the soil and replenishes the water table versus the amount that contributes to surface runoff and to channel flow. However observations of soil moisture at a point scale are very sparse and observing networks are expensive to maintain. Satellite sensors can observe large areas but the spatial resolution of these is dependent on microwave frequency, antenna dimensions, and height above the earth’s surface. The higher the sensor, the lower the spatial resolution and at low elevations the spacecraft would use more fuel. Higher spatial resolution requires larger diameter antennas that in turn require more fuel to maintain in space. Given these competing issues most passive radiometers have spatial resolutions in 10s of kilometers that are too coarse for catchment hydrology applications. Most local applications require higher-spatial-resolution soil moisture data. Downscaling of the data requires ancillary data and model products, all of which are used here to develop high-spatial-resolution soil moisture for catchment applications in hydrology. In this paper the author will outline and explain the methodology for downscaling passive microwave estimation of soil moisture.
Analysis of Fast Radix-10 Digit Recurrence Algorithms for Fixed-Point and Floating-Point Dividers on FPGAs
Authors: Baesler Malte , Voigt Sven-Ole
Published: March 2013

Decimal floating point operations are important for applications that cannot tolerate errors from conversions between binary and decimal formats, for instance, commercial, financial, and insurance applications. In this paper we present five different radix-10 digit recurrence dividers for FPGA architectures. The first one implements a simple restoring shift-and-subtract algorithm, whereas each of the other four implementations performs a nonrestoring digit recurrence algorithm with signed-digit redundant quotient calculation and carry-save representation of the residuals. More precisely, the quotient digit selection function of the second divider is implemented fully by means of a ROM, the quotient digit selection function of the third and fourth dividers are based on carry-propagate adders, and the fifth divider decomposes each digit into three components and requires neither a ROM nor a multiplexer. Furthermore, the fixed-point divider is extended to support IEEE 754-2008 compliant decimal floating-point division for decimal64 data format. Finally, the algorithms have been synthesized on a Xilinx Virtex-5 FPGA, and implementation results are given.
A Case of Traumatic Proptosis
Authors: Desai Bobby
Published: March 2013

We present a case of traumatic proptosis in a competitive football player. This entity can occur with a significant decrease in vision, but in this case it did not. Some other causes of this condition are also discussed. A review of some traumatic conditions that may cause proptosis is provided as well.
Clinical and Radiographic Evaluation of Brånemark Implants with an Anodized Surface following Seven-to-Eight Years of Functional Loading
Authors: Gelb David , McAllister Bradley , Nummikoski Pirkka , Del Fabbro Massimo
Published: March 2013

The aim of this study was to evaluate the clinical and radiographic long-term outcomes of dental implants with an anodized TiUnite surface, placed in routine clinical practice. Two clinical centers participated in the study. One hundred and seven implants (80 in the maxilla and 27 in the mandible) in 52 patients were followed in the long term. Both one- and two-stage techniques were used for 38 and 69 implants, respectively. Thirty-eight single tooth restorations and 22 fixed partial prostheses were delivered, according to a delayed loading protocol, within 4 to 12 months since implant placement. All implants were stable at insertion and at the long-term follow-up visit, which occurred between 7 and 8 years of functional loading. The mean followup was7.33±0.47years. The mean marginal bone level change at the long-term followup as compared to baseline was1.49±1.03 mm. No implant failure occurred. Healthy peri-implant mucosa was found around 95% of implants, whereas 91% of implants showed no visible plaque at the implant surfaces at the long-term followup. The study showed that dental implants with the TiUnite anodized surface demonstrate excellent long-term clinical and radiographic outcomes.
About a Partial Differential Equation-Based Interpolator for Signal Envelope Computing: Existence Results and Applications
Authors: Niang Oumar , Thioune Abdoulaye , Deléchelle Éric , Niane Mary Teuw , Lemoine Jacques
Published: March 2013

This paper models and solves the mathematical problem of interpolating characteristic points of signals by a partial differential Equation-(PDE-) based approach. The existence and uniqueness results are established in an appropriate space whose regularity is similar to cubic spline one. We show how this space is suitable for the empirical mode decomposition (EMD) sifting process. Numerical schemes and computing applications are also presented for signal envelopes calculation. The test results show the usefulness of the new PDE interpolator in some pathological cases like input class functions that are not so regular as in the cubic splines case. Some image filtering tests strengthen the demonstration of PDE interpolator performance.
Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting
Authors: Perche Federico , Torchilin Vladimir P.
Published: March 2013

Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.
Music Identification System Using MPEG‐7 Audio Signature Descriptors
Authors: You Shingchern D. , Chen Wei-Hwa , Chen Woei-Kae
Published: March 2013

This paper describes a multiresolution system based on MPEG‐7 audio signature descriptors for music identification. Such an identification system may be used to detect illegally copied music circulated over the Internet. In the proposed system, low‐resolution descriptors are used to search likely candidates, and then full‐resolution descriptors are used to identify the unknown (query) audio. With this arrangement, the proposed system achieves both high speed and high accuracy. To deal with the problem that a piece of query audio may not be inside the system’s database, we suggest two different methods to find the decision threshold. Simulation results show that the proposed method II can achieve an accuracy of 99.4% for query inputs both inside and outside the database. Overall, it is highly possible to use the proposed system for copyright control.
Enhanced Photocatalytic Activity of ZrO2-SiO2Nanoparticles by Platinum Doping
Authors: Kadi Mohammad W. , Mohamed R. M.
Published: March 2013

ZrO2-SiO2mixed oxides were prepared via the sol-gel method. Photo-assisted deposition was utilized for doping the prepared mixed oxide with 0.1, 0.2, 0.3, and 0.4 wt% of Pt. XRD spectra showed that doping did not result in the incorporation of Pt within the crystal structure of the material. UV-reflectance spectrometry showed that the band gap of ZrO2-SiO2decreased from 3.04 eV to 2.48 eV with 0.4 wt% Pt doping. The results show a specific surface area increase of 20%. Enhanced photocatalysis of Pt/ZrO2-SiO2was successfully tested on photo degradation of cyanide under illumination of visible light. 100% conversion was achieved within 20 min with 0.3 wt% of Pt doped ZrO2-SiO2.
Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells
Authors: Arpicco Silvia , De Rosa Giuseppe , Fattal Elias
Published: March 2013

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems.
Depression after Stroke and Risk of Mortality: A Systematic Review and Meta-Analysis
Authors: Bartoli Francesco , Lillia Nicoletta , Lax Annamaria , Crocamo Cristina , Mantero Vittorio , Carrà Giuseppe , Agostoni Elio , Clerici Massimo
Published: March 2013

Background.Depression after stroke may have great burden on the likelihood of functional recovery and long-term outcomes.Objective. To estimate the association between depression after stroke and subsequent mortality.Methods. A systematic search of articles using PubMed and Web of Science databases was performed. Odds ratios (ORs) and hazard ratios (HRs) were used as association measures for pooled analyses, based on random-effects models.Results. Thirteen studies, involving 59,598 subjects suffering from stroke (6,052 with and 53,546 without depression), had data suitable for meta-analysis. The pooled OR for mortality at followup in people suffering from depression after stroke was 1.22 (1.02–1.47). Subgroups analyses highlighted that only studies with medium-term followup (2–5 years) showed a statistically significant association between depression and risk of death. Four studies had data suitable for further analysis of pooled HR. The meta-analysis revealed a HR for mortality of 1.52 (1.02–2.26) among people with depression after stroke.Conclusions. Despite some limitations, this paper confirms the potential role of depression on post stroke mortality. The relationship between depression and mortality after stroke seems to be related to the followup duration. Further research is needed to clarify the nature of the association between depression after stroke and mortality.
Annealing Effects of Sputtered Cu2O Nanocolumns on ZnO‐Coated Glass Substrate for Solar Cell Applications
Authors: Chen Lung-Chien , Wang Chung-Chieh , Lu Suz-Wei
Published: March 2013

Cuprous oxide (Cu2O) films were prepared on an indium tin oxide glass substrate by radiofrequency magnetron sputtering using a high‐purity Cu target. The temperature of annealing was varied to obtain Cu2O thin films with various elements, compositions, and surface structures. The p‐Cu2O thin films thus formed were characterized by FESEM and XRD. After annealing at 500∘C, the bilayer structure which consisted of Cu nanoclusters on the surface of a film of Cu2O nanocolumns was observed. The Cu2O solar cell with the bilayered structure exhibited poor power conversion efficiency.
Firm’s Decisions Based on Consumers’ Choices in Ecocertified Food Markets
Authors: Karipidis Philippos , Sartzetakis Eftichios
Published: March 2013

The present paper proposes a framework for examining whether a food production enterprise, attempting to build an ecocertification strategy, connects the creation of environmental value with the creation of economic value, balancing environmental sustainability with economic sustainability. More specifically, the paper combines demand theory with a discreet choice consumers’ model in an embryonic ecocertified food market, to examine whether economic value is created and to identify the determinants of this value creation. An empirical investigation of the model using consumer data indicates that a variety of factors, such as consumer’s age and profession, family’s income and purchasing strategy, product quality association in consumers’ mind and the retailing outlet, play an important role in shaping the respondents’ intention to pay for the ecofriendliness of products. The proposed framework can help enterprise management to balance the consumers’ and enterprise owners’ claims in cases where certification schemes or standards exist that enable enterprises to communicate social responsibility to their customers.
Development and Evaluation of Automotive Speech Interfaces: Useful Information from the Human Factors and the Related Literature
Authors: Lo Victor Ei-Wen , Green Paul A.
Published: March 2013

Drivers often use infotainment systems in motor vehicles, such as systems for navigation, music, and phones. However, operating visual-manual interfaces for these systems can distract drivers. Speech interfaces may be less distracting. To help designing easy-to-use speech interfaces, this paper identifies key speech interfaces (e.g., CHAT, Linguatronic, SYNC, Siri, and Google Voice), their features, and what was learned from evaluating them and other systems. Also included is information on key technical standards (e.g., ISO 9921, ITU P.800) and relevant design guidelines. This paper also describes relevant design and evaluation methods (e.g., Wizard of Oz) and how to make driving studies replicable (e.g., by referencing SAE J2944). Throughout the paper, there is discussion of linguistic terms (e.g., turn-taking) and principles (e.g., Grice’s Conversational Maxims) that provide a basis for describing user-device interactions and errors in evaluations.
Downregulation of Hepatoma-Derived Growth Factor Contributes to Retarded Lung Metastasis via Inhibition of Epithelial–Mesenchymal Transition by Systemic POMC Gene Delivery in Melanoma
Authors: Tsai Han-En , Liu Guei-Sheung , Kung Mei-Lang , Liu Li-Feng , Wu Jian-Ching , Tang Chia-Hua , Huang Ching-Hui , Chen San-Cher , Lam Hing-Chung , Wu Chieh-Shan , Tai Ming-Hong
Published: March 2013

The prognosis of malignant melanoma is poor due to high incidence of metastasis, underscoring the demand for development of novel therapeutic strategies. Stress hormone pro-opiomelanocortin (POMC) is the precursor for several anti-inflammatory peptides that hold promise for management of cancer-related diseases. The present study evaluated the antimetastatic potential and mechanism of POMC therapy for metastatic melanoma. Adenovirus-mediated POMC gene delivery potently inhibited the invasiveness of human and mouse melanoma cells. Moreover, after induction of lung metastasis, systemic POMC expression significantly reduced the foci formation and neovascularization in lungs. Mechanistic studies revealed that POMC therapy inhibited the epithelial–mesenchymal transition (EMT) of melanoma cells by upregulation of E-cadherin and downregulation of vimentin and α-smooth muscle actin (α-SMA). In addition, microarray analysis unveiled POMC gene transfer reduced the mRNA level of multiple prometastatic factors, including hepatoma-derived growth factor (HDGF). Cell culture and immunohistochemical studies further confirmed that POMC gene delivery significantly decreased the expression of HDGF in melanoma cells and tissues. Despite stimulating the invasion and EMT, exogenous HDGF supply only partially attenuated the POMC-mediated invasion inhibition and EMT change in melanoma cells. Finally, we delineated the contribution of melanocortins to POMC-induced inhibition of invasion, HDGF downregulation, and E-cadherin upregulation. Together, these results indicate that HDGF downregulation participates in POMC-induced suppression of metastasis and EMT in melanoma. Mol Cancer Ther; 12(6); 1016–25. ©2013 AACR.
mda-7/IL-24 Expression Inhibits Breast Cancer through Upregulation of Growth Arrest-Specific Gene 3 (gas3) and Disruption of β1 Integrin Function
Authors: Li You-Jun , Liu Guodong , Li Yanmei , Vecchiarelli-Federico Laura M. , Liu Jeff C. , Zacksenhaus Eldad , Shan Sze W. , Yang Burton B. , Li Qi , Dash Rupesh , Fisher Paul B. , Archer Michael C. , Ben-David Yaacov
Published: March 2013

Melanoma differentiation-associated gene (MDA)-7)/interleukin (IL)-24, a member of the IL-10 family of cytokines, inhibits growth of various human cancer cells, yet the underlying mechanism is largely unknown. Here, we report that mda-7/IL-24 efficiently suppresses the development of rat mammary tumors in vivo. Microarray analysis for genes differentially expressed in rat mammary tumor cells overexpressing MDA-7/IL-24 compared with those that do not express this cytokine identified growth arrest-specific gene-3 (gas3) as a target for mda-7/IL-24. Upregulation of gas3 by mda-7/IL-24 was STAT3 dependent. Induction of gas3 inhibited attachment and proliferation of tumor cells in vitro and in vivo by inhibiting the interaction of β1 integrin with fibronectin. A mutated GAS3, which is unable to bind β1 integrin, was also unable to inhibit fibronectin-mediated attachment and cell growth both in adherent and suspension cultures, suggesting that GAS3 exerts its effects through interaction with and regulation of β1 integrin. Thus, mda-7/IL-24 inhibits breast cancer growth, at least in part, through upregulation of GAS3 and disruption of β1 integrin function. Importantly, the expression of the mda-7/IL-24 receptor, IL-20R1, is highly correlated with GAS3 expression in human breast cancer (P = 1.02 × 10−9), and the incidence of metastases is significantly reduced in patients with HER2+ breast cancer expressing high-levels of IL-20R1. Together, our results identify a novel MDA-7/IL-24-GAS3-β1integrin–fibronectin signaling pathway that suppresses breast cancer growth and can be targeted for therapy. Mol Cancer Res; 11(6); 593–603. ©2013 AACR.
Glyoxylate Reductase/Hydroxypyruvate Reductase: A Novel Prognostic Marker for Hepatocellular Carcinoma Patients after Curative Resection
Authors: Pan Yinglian , Ni Runzhou , Deng Qingchun , Huang Xiaodong , Zhang Yixin , Lu Cuihua , Li Feifei , Huang Da , He Song , Chen Buyou
Published: March 2013

Objective: Glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a key enzyme in the glyoxylate cycle. Its deficiency causes primary hyperoxaluria type 2. We first noticed that GRHPR was also lost in human hepatocellular carcinoma (HCC) and proliferative HCC cells. The aim of the present study was to investigate the potential clinical utility of GRHPR in HCC. Methods: The expression of GRHPR in tissues and cells was detected by Western blotting. Immunohistochemistry was utilized to examine the expression patterns of GRHPR and Ki-67 in a surgical cohort of HCC and adjacent liver tissues. Results: We demonstrated that GRHPR showed a lower expression in tumor tissues than in nontumoral tissues. GRHPR was negatively correlated with Ki-67 (R2 = 0.771, p < 0.05) and GRHPR was reduced in proliferative Huh7 cells (p < 0.05). Patients with negative GRHPR both in tumor tissues and nontumoral tissues had a significantly shorter survival time than those with positive GRHPR (p < 0.001). Multivariate analysis established that GRHPR was detected in nontumoral tissues as an independent prognostic factor for patients with HCC. Conclusions: Our findings suggest that the GRHPR defect in noncancerous tissues may represent an independent predictor of poor survival for HCC patients after curative resection and that there may be a link between GRHPR and prognosis of HCC patients.
Thalidomide Combined with Neoadjuvant Chemotherapy in Angiosarcoma of the Breast with Complete Pathologic Response: Case Report and Review of Literature
Authors: Alvarado-Miranda Alberto , Bacon-Fonseca Ludwing , Lara-Medina Fernando Ulises , Maldonado-Martínez Hector , Arce-Salinas Claudia
Published: March 2013

Background: Primary angiosarcoma of the breast is a rare malignancy. Case Report: We report on a 41-year-old female patient who initially presented with locally advanced disease. Core biopsy showed angiosarcoma of the breast, grade 1, CD31-positive. The patient was treated with neoadjuvant systemic chemotherapy based on cisplatin, doxorubicin, and paclitaxel, given concurrently with thalidomide. After treatment completion, the patient underwent radical mastectomy. Pathologic complete response in the breast and axillary lymph nodes was achieved. The patient has no evidence of disease recurrence 6 months after her initial diagnosis. Conclusion: Anti-angiogenic therapy may be considered as part of the management of primary angiosarcoma of the breast
Side Effects of Standard Adjuvant and Neoadjuvant Chemotherapy Regimens According to Age Groups in Primary Breast Cancer
Authors: Reinisch Mattea , von Minckwitz Gunter , Harbeck Nadia , Janni Wolfgang , Kümmel Sherko , Kaufmann Manfred , Elling Dirk , Nekljudova Valentina , Loibl Sibylle
Published: March 2013

Background: Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination. Patients and Methods: In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age. Results: Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60-64 years and 10.6% were > 64 years. The patients' compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC- and dd-doxorubicin/docetaxel-treated groups. Conclusion: The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years.
Relevance of Health Economics in the Medical Treatment of Breast Cancer: The View of the Professional Association of Practicing Gynecologic Oncologists e.V. (BNGO)
Authors: Heinrich Georg , Hindenburg Hans-Joachim , Schilling Jörg , Klare Peter
Published: March 2013

In this article, the position of the Professional Association of Practicing Gynecologic Oncologists e.V. (BNGO) on the health economics of medical breast cancer therapy is presented. The BNGO unites professionals and employees whose principal activity lies in highly specialized gynecologic oncology. In Germany, 139 specialists are united in 128 professional practices. According to § 12 of the Social Code, the oncological services provided by members must be ‘sufficient, effective and economical; they must not exceed what is necessary'. People who are covered by statutory health insurance in Germany are entitled to sufficient benefits. Sufficient measures are measures that benefit the patient with breast cancer and have a positive effect on the course of the disease. In § 35b of the Social Code, the benefit of the patient is defined as ‘improvement in health, shortening of the duration of illness, lengthening of lifespan, reduction of side effects and an improvement in the quality of life'. In the adjuvant situation, the ideal goal is healing; in the palliative situation, the most basic marker is overall survival, while surrogate markers are the progression-free interval, improved quality of life, or diminished symptoms. At the same time, the law on economic assessment stipulates ‘appropriateness and reasonableness of reimbursement by the insured community'.
Relevance of Health Economics in Breast Cancer Treatment - the View of Certified Breast Centres and Their Patients
Authors: Lux Michael , Hildebrandt Thomas , Beyer-Finkler Elke , Bani Mayada , Loehberg Christian , Jud Sebastian , Rauh Claudia , Schrauder Michael , Fasching Peter , Beckmann Matthias
Published: March 2013

Breast cancer centres - certified in accordance with the criteria of the German Cancer Association and the German Mastology Association - are established throughout Germany. Although the setting up of centres and the subsequent need for certification are associated with a marked increase in costs, initial data show positive effects on quality. Certified centres are cost-effective from the point of view of health economics - they lead to improved quality in processes and results without creating any increase in costs for the funding bodies. However, the organization of the necessary structures, with interdisciplinary treatment, documentation and quality-assurance measures, requires considerable resources. Increasing consolidation of inpatient services is also involved, while shortening of the patients' hospitalization periods is leading to reduced remuneration from the funding bodies. The current cost deficits, which have resulted from the increased resources required, need to be recouped through additional charges. It will only be possible to maintain the high quality achieved if additional charges become available to cover the centres' added costs. Good data are increasingly becoming available as a basis for negotiations on charges - e.g., with regard to the quality of results and the National Cancer Plan - as well as clear support from patients.
Apathy Is Associated with Activities of Daily Living Ability in Parkinson's Disease
Authors: Laatu S. , Karrasch M. , Martikainen K. , Marttila R.
Published: March 2013

Background: Neuropsychiatric symptoms and impairment in performing activities of daily living (ADL) in patients with Parkinson's disease (PD) are strong predictors of the overall caregiver burden and they increase the risk for nursing home admission of the patients. The purpose of the present study was to assess the association of neuropsychiatric symptoms and ADL functions in PD. Methods: A total of 73 community-dwelling PD patients were studied. The mean age of the patient group was 65 years and the mean disease duration was 9 years. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and ADL abilities were measured by the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Results: The prevalence of neuropsychiatric symptoms in patients with PD was 73%. The most common symptoms were depression, anxiety, irritability, apathy and agitation. ADL ability correlated significantly with apathy (p < 0.002) even when adjusted for motor symptoms. Conclusion: Apathy was significantly associated with ADL in PD. The result indicates that more attention should be paid to identifying apathy and targeting therapeutic interventions.
Sex Differentiation in an All-Female (XX) Rainbow Trout Population with a Genetically Governed Masculinization Phenotype
Authors: Valdivia K. , Mourot B. , Jouanno E. , Volff J.-N. , Galiana-Arnoux D. , Guyomard R. , Cauty C. , Collin B. , Rault P. , Helary L. , Fostier A. , Quillet E. , Guiguen Y.
Published: March 2013

Sex determination is known to be male heterogametic in the rainbow trout, Oncorhynchus mykiss; however, scattered observations that deviate from this rather strict genetic control have been reported. Here, we provide a detailed morphological and histological characterization of the gonadal differentiation and development (from 43 days postfertilization to 11 months of age) in an all-female (XX) population with a genetically governed masculinization phenotype. In comparison with control males and females, the gonadal differentiation in these animals was characterized by many perturbations, including significantly fewer germ cells. This decrease in germ cells was confirmed by the significantly decreased expression of 2 germ cell maker genes (vasa and sycp3) in the masculinized XX populations as compared with the control females and control males. Although only a proportion of the total adult population was partially or fully masculinized, this early differentiating phenotype affected nearly all the sampled animals. This suggests that the adult masculinization phenotype is the consequence of an early functional imbalance in ovarian differentiation in the entire population. We hypothesize that the lower number of germ cells that we observed in this population could be one cause of their masculinization.
Expression of Rac1, HIF-1α, and VEGF in Gastric Carcinoma: Correlation with Angiogenesis and Prognosis
Authors: Zhan Hongjie , Liang Han , Liu Xiangyu , Deng Jingyu , Wang Baogui , Hao Xishan
Published: March 2013

Background: The aim of this study was to investigate the relationship between the expression of hypoxia-inducible factor-1α (HIF-1α), Ras-related C3 botulinum toxin substrate 1 (Rac1), and vascular endothelial growth factor (VEGF), as well as their correlation with angiogenesis and prognosis in gastric carcinoma. Material and Methods: The expression of Rac1, HIF-1α, VEGF, and CD34 (described in terms of microvessel density, MVD) was determined by immunohistochemical staining of tissues from 60 radically resected gastric cancer specimens. Results: The proportion of specimens expressing Rac1, HIF-1α, and VEGF was 37/60 (61.7%), 35/60 (58.3%), and 40/60 (66.7%), respectively. The levels of Rac1, HIF-1α, and VEGF expression were significantly correlated with Lauren's classification, lymph node metastasis, and pathologic staging (p < 0.05). There were positive correlations between MVD and the expression of Rac1, HIF-1α, and VEGF. The mean survival time and 5-year survival rate in cases with positive Rac1, HIF-1α, and VEGF expression and MVD ≥ 26.3 were significantly shorter than those with negative Rac1, HIF-1α, and VEGF expression and MVD < 26.3. Conclusion: Rac1, HIF-1α, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis. Thus, testing the expression of Rac1, HIF-1α, and VEGF may be a useful index for treatment and prognosis.
Metastatic Breast Carcinoma Presenting as a Sigmoid Stricture: Report of a Case and Review of the Literature
Authors: Nikkar-Esfahani A. , Kumar Bhaskar G. , Aitken Douglas , Wilson Robert G.
Published: March 2013

Metastatic spread of breast carcinoma to the colon and rectum is rare. We report the case of a patient treated for lobular breast carcinoma presenting 17 years later with metastatic breast cancer of the colon. A 63-year-old lady with a past history of right-sided invasive lobular carcinoma of the breast presented with persistent diarrhoea. Colonoscopy with biopsies revealed a benign-looking stricture at the rectosigmoid junction. A CT scan of the abdomen and pelvis revealed a benign-looking stricture in keeping with a probable diverticular stricture. A Hartmann procedure was performed and histology revealed a metastatic lobular carcinoma with oestrogen and progesterone receptor-positive status. Treatment was commenced with letrozole and the patient remains well under clinical surveillance. In a patient with a history of breast carcinoma who presents with gastrointestinal symptoms the possibility of gastrointestinal tract spread should always be considered. Endoscopic diagnosis may be misleading with pathological diagnosis only being made following surgical resection. A history of breast carcinoma must be declared to the histopathologist following surgical resection so that an accurate diagnosis is made and appropriate treatment is commenced.
Encapsulating Peritoneal Sclerosis: A Rare Complication of Peritoneal Dialysis in Al-Ain, United Arab Emirates
Authors: Abouchacra Samra , Chaaban Ahmed , Sajwani Suad , Bashir Mohammad , Beghdash Omar , Abdulle Abdishakur
Published: March 2013

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) with devastating consequences. Although it can occur among patients on PD, it may present long after PD has been discontinued; thus, its diagnosis depends on a high index of suspicion. We present a rare case of EPS in the United Arab Emirates with a protracted course and delays in recognizing the condition until after resolution of the acute attack. This case highlights the need for early identification of risk factors as well as the subtle features of EPS for appropriate diagnosis and perhaps even prevention; this being worth a ton of cure. A review of the literature including the latest evidence-based treatment options is also highlighted.
Enterobacter cloacae Postsurgical Endophthalmitis: Report of a Positive Outcome
Authors: Butikofer Scott , Dettori Jason M. , Vemulakonda G. Atma , Slabaugh Mark
Published: March 2013

We report a positive outcome of postcataract endophthalmitis caused by Enterobacter cloacae, which has previously resulted in poor outcomes in endophthalmitis. A 67-year-old man underwent uncomplicated cataract surgery. On the morning of postoperative day (POD) #1, he had significant anterior chamber inflammation without pain, hypopyon, or vitritis but then rapidly developed hypopyon and worsening visual acuity. He underwent a tap and inject with vancomycin and ceftazidime and was prescribed topical steroids and antibiotics as well as oral levofloxacin. On POD #3, cultures of the vitreous and aqueous returned positive for E. cloacae. By POD #6, his hypopyon had resolved with improved vitritis, decreased inflammation, and visual acuity of 20/200. Two weeks after surgery, his best-corrected visual acuity was 20/60. Contrary to prior reports, we demonstrate that it is possible to achieve a good outcome in cases of E. cloacae endophthalmitis treated early with appropriate antibiotics and anti-inflammatory agents.