bluuebunny/crossref_metadata_2025 huggingface dataset:
Percutaneous Nephrolithotomy in Children
Authors: DeMarco Romano T.
Published: October 2011

The surgical management of pediatric stone disease has evolved significantly over the last three decades. Prior to the introduction of shockwave lithotripsy (SWL) in the 1980s, open lithotomy was the lone therapy for children with upper tract calculi. Since then, SWL has been the procedure of choice in most pediatric centers for children with large renal calculi. While other therapies such as percutaneous nephrolithotomy (PNL) were also being advanced around the same time, PNL was generally seen as a suitable therapy in adults because of the concerns for damage in the developing kidney. However, recent advances in endoscopic instrumentation and renal access techniques have led to an increase in its use in the pediatric population, particularly in those children with large upper tract stones. This paper is a review of the literature focusing on the indications, techniques, results, and complications of PNL in children with renal calculi.
Effect of Applied Potential on the Formation of Self-OrganizedTiO2Nanotube Arrays and Its Photoelectrochemical Response
Authors: Lai Chin Wei , Sreekantan Srimala
Published: October 2011

Self-organized TiO2nanotube arrays have been fabricated by anodization of Ti foil in an electrochemical bath consisting of 1 M of glycerol with 0.5 wt% of NH4F. The effects of applied potential on the resulting nanotubes were illustrated. Among all of the applied potentials, 30 V resulted in the highest uniformity and aspect ratio TiO2nanotube arrays with the tube's length approximately 1 μm and pore's size of 85 nm. TiO2nanotube arrays were amorphous in as-anodized condition. The anatase phase was observed after annealing at 400∘Cin air atmosphere. The effect of crystallization and effective surface area of TiO2nanotube arrays in connection with the photoelectrochemical response was reported. Photoelectrochemical response under illumination was enhanced by using the annealed TiO2nanotube arrays which have larger effective surface area to promote more photoinduced electrons.
Investigation of Rotating MHD Viscous Flow and Heat Transfer between Stretching and Porous Surfaces Using Analytical Method
Authors: Sheikholeslami M. , Ashorynejad H. R. , Ganji D. D. , Kolahdooz A.
Published: October 2011

Hydromagnetic flow between two horizontal plates in a rotating system, where the lower plate is a stretching sheet and the upper is a porous solid plate, is analyzed. Heat transfer in an electrically conducting fluid bonded by two parallel plates is studied in the presence of viscous dissipation. The equations of conservation of mass and momentum and energy are reduced to a nonlinear ordinary differential equations system. Homotopy perturbation method is used to get complete analytic solution for velocity and temperature profiles. Results show an acceptable agreement between this method results and numerical solution. Also the effects of different parameters are discussed through graphs.
Involvement of Indoleamine 2,3-Dioxygenase in Impairing Tumor-Infiltrating CD8+T-Cell Functions in Esophageal Squamous Cell Carcinoma
Authors: Zhang Ge , Liu Wan-Li , Zhang Lin , Wang Jun-Ye , Kuang Miao-Huan , Liu Peng , Lin Yue-Hao , Dai Shu-Qin , Du Jun
Published: October 2011

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.
B7-H4 Pathway in Islet Transplantation andβ-Cell Replacement Therapies
Authors: Wang Xiaojie , Hao Jianqiang , Metzger Daniel L. , Ao Ziliang , Meloche Mark , Verchere C. Bruce , Chen Lieping , Ou Dawei , Mui Alice , Warnock Garth L.
Published: October 2011

Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency.β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients. T cells play a central role in determining the outcome of both autoimmune responses and allograft survival. B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models. B7-H4 protects allograft survival and generates donor-specific tolerance. It also prevents the development of autoimmune diabetes. More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4 : B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses.
Spectroscopic Studies of Distorted Structure Systems in the Vibron Model: Application to Porphyrin and Its Isotopomers
Authors: Karumuri Srinivasa Rao , Jallaparthi Vijayasakhar , Venigalla Sreeram
Published: October 2011

We have introduced an algebraic technique to biomolecules (porphyrins) family to determine the vibrational spectra. We present an algebraic model of vibrations of polyatomic biomolecules, as an example, the vibrational analysis of stretching modes of nickel octaetheylporphyrin (Ni(OEP)) and its isotopomers. The algebraic technique obtained the results are compared with experimental data; the results are showing good accuracy. Some reassignments of energy levels that predict location of energy states not yet observed.
Determination of Low Levels of Lead in Beer Using Solid-Phase Extraction and Detection by Flame Atomic Absorption Spectrometry
Authors: Alves Vanessa N. , Borges Simone S. O. , Neto Waldomiro B. , Coelho Nívia M. M.
Published: October 2011

In this study, a method for the determination of low concentrations of lead in beer samples using solid-phase extraction with a flow injection analysis system and detection by flame atomic absorption spectrometry (FAAS) was developed.Moringa oleiferaseeds were used as a biosorbent material. Chemical and flow variables of the online preconcentration system, such as sample pH, preconcentration flow rate, eluent flow rate, eluent concentration, particle size, and sorbent mass, were studied. The optimum extraction conditions were obtained using a sample pH of 6.0, sample flow rate of 6.0 mL min−1, 63.0 mg of sorbent mass, and 2.0 mol L−1HNO3at a flow rate of 2.0 mL min−1as the eluent. With the optimized conditions, the preconcentration factor, precision, detection limit, consumption index, and sample throughput were estimated as 93, 0.3% (10.0 μg L−1,n=7), 7.5 μg L−1, 0.11 mL, and 23 samples per hour, respectively. The method developed was successfully applied to beer samples and recovery tests, with recovery ranging from 80% to 100%.
Potentiometric Determination of Ketotifen Fumarate in Pharmaceutical Preparations and Urine Using Carbon Paste and PVC Membrane Selective Electrodes
Authors: Frag Eman Y. Z. , Mohamed Gehad G. , Khalil Mohamed M. , Hwehy Mohammad M. A.
Published: October 2011

This study compares between unmodified carbon paste (CPE; the paste has no ion pair) and polyvinyl chloride (PVC) membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF), where sodium tetraphenylborate (NaTPB) was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10−7to 10−2 mol L−1. The electrodes show Nernstian slope value of and  mV decade−1for CPE and PVC membrane electrodes at 30∘C, respectively. The potential is nearly stable over the pH range 3.0–6.0 and 2.0–7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets), and biological fluid (urine). The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of and with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.
Transient Presyncope Secondary to Posterior Descending Artery Occlusion
Authors: Moffat Andrew D. , Al-Khatib Jamal T. , Michael Jennifer , Nguyen Vien X.
Published: October 2011

We describe the case of a 64-year-old male initially presenting with presyncope and bradycardia, without any anginal symptoms or objective evidence of myocardial ischemia. A stress test induced no physical symptoms but revealed a left bundle branch block with multiple preventricular contractions on electrocardiogram. Subsequent catheterization revealed severe obstructive disease throughout the coronary arteries. He was treated percutaneously on two separate heart catheterizations. The presyncope and bradycardia resolved after reperfusion of the posterior descending artery.
A Comparative Study of the Common Protozoan Parasites ofClarias gariepinusfrom the Wild and Cultured Environments in Benue State, Nigeria
Authors: Omeji S. , Solomon S. G. , Idoga E. S.
Published: October 2011

A total of one hundred and twentyClarias gariepinuscomprising 30 dead and 30 live fishes were examined for protozoan parasites infestation, sixty each from the wild and a pond (cultured environment) over a period of six months.Ichthyophthirius multifiliiswas the most common protozoan parasites found inC. gariepinusfrom the wild (River Benue) and cultured (pond) environments. These protozoan parasites constitute 37.08% of the total parasites encountered for fishes in the pond and 42.51% of fishes in the wild. Among the body parts of the sampled fishes from the pond, the gills had the highest parasite load (38.86%). Also, the gills had the highest parasite load (40.54%) among the body parts of the fishes sampled from the wild. Fishes not infested with any protozoan parasites from the pond constituted 36.70% of the total fish sampled. On the other hand, fishes not infested with any protozoan parasites from the wild constituted 31.65% of the total fish sampled. Female fishes had more protozoan parasites than the male fishes. Bigger fishes of total length (25–48 cm) had more parasite load than the smaller ones (19–24 cm). Also, fishes between 150–750 g had more parasite load than the smaller ones of less than 150 g. Protozoan parasite load of fish from the cultured environment (pond) did not differ significantly (P<0.05) from those from River Benue (wild).
Comparison of Probabilistic Chain Graphical Model-Based and Gaussian Process-Based Observation Selections for Wireless Sensor Scheduling
Authors: Qi Qi , Shang Yi
Published: October 2011

The constrained power source given by batteries has become one of the biggest hurdles for wireless sensor networks to prevail. A common technique to reduce energy consumption is to put sensors to sleep between duties. It leads to a tradeoff between making a fewer number of observations for saving energy while obtaining sufficient and more valuable sensing information. In this paper, we employ two model-based approaches for tackling the sensor scheduling problem. The first approach is to apply our corrected VoIDP algorithm on a chain graphical model for selecting a subset of observations that minimizes the overall uncertainty. The second approach is to find a selection of observations based on Gaussian process model that maximizes the entropy and the mutual information criteria, respectively. We compare their performances in terms of predictive accuracies for the unobserved time points based on their selections of observations. Experimental results show that the Gaussian process model-based method achieves higher predictive accuracy if sensor data are accurate. However, when observations have errors, its performance degrades quickly. In contrast, the graphical model-based approach is more robust and error tolerant.
Indirect Effects of Oral Tolerance Inhibit Pulmonary Granulomas toSchistosoma mansoniEggs
Authors: Azevedo Geraldo Magela , Costa Raquel Alves , Resende Mariana Araujo , Rodrigues Claudiney Melquiades , Vaz Nelson Monteiro , Carvalho Cláudia Rocha
Published: October 2011

Parenteral injection of tolerated proteins into orally tolerant mice inhibits the initiation of immunological responses to unrelated proteins and blocks severe chronic inflammatory reactions of immunological origin, such as autoimmune reactions. This inhibitory effect which we have called “indirect effects of oral tolerance” is also known as “bystander suppression.” Herein, we show that i.p. injection of OVA + Al(OH)3minutes before i.v. injection ofSchistosoma mansonieggs into OVA tolerant mice blocked the increase of pulmonary granulomas. In addition, the expression of ICAM-1 in lung parenchyma in areas outside the granulomas of OVA-orally tolerant mice was significantly reduced. However, at day 18 after granuloma induction there was no difference in immunofluorescency intensity to CD3, CD4, F4/80, andα-SMA per granuloma area of tolerant and control groups. Reduction of granulomas by reexposure to orally tolerated proteins was not correlated with a shift in Th-1/Th-2 cytokines in serum or lung tissue extract.
Targeting Endothelial Dysfunction in Vascular Complications Associated with Diabetes
Authors: Sharma Arpeeta , Bernatchez Pascal N. , de Haan Judy B.
Published: October 2011

Cardiovascular complications associated with diabetes remain a significant health issue in westernized societies. Overwhelming evidence from clinical and laboratory investigations have demonstrated that these cardiovascular complications are initiated by a dysfunctional vascular endothelium. Indeed, endothelial dysfunction is one of the key events that occur during diabetes, leading to the acceleration of cardiovascular mortality and morbidity. In a diabetic milieu, endothelial dysfunction occurs as a result of attenuated production of endothelial derived nitric oxide (EDNO) and augmented levels of reactive oxygen species (ROS). Thus, in this review, we discuss novel therapeutic targets that either upregulate EDNO production or increase antioxidant enzyme capacity in an effort to limit oxidative stress and restore endothelial function. In particular, endogenous signaling molecules that positively modulate EDNO synthesis and mimetics of endogenous antioxidant enzymes will be highlighted. Consequently, manipulation of these unique targets, either alone or in combination, may represent a novel strategy to confer vascular protection, with the ultimate goal of improved outcomes for diabetes-associated vascular complications.
Treatment of Hematologic Malignancies with Immunotoxins and Antibody-Drug Conjugates
Authors: FitzGerald David J. , Wayne Alan S. , Kreitman Robert J. , Pastan Ira
Published: October 2011

To enable antibodies to function as cytotoxic anticancer agents, they are modified either via attachment to protein toxins or highly potent, low-molecular-weight drugs. Such molecules, termed immunotoxins and antibody-drug conjugates, respectively, represent a second revolution in antibody-mediated cancer therapy. Thus, highly toxic compounds are delivered to the interior of cancer cells based on antibody specificity for cell-surface target antigens. Cancer Res; 71(20); 6300–9. ©2011 AACR.
Hepatitis B Virus Large Surface Antigen Promotes Liver Carcinogenesis by Activating the Src/PI3K/Akt Pathway
Authors: Liu Haiou , Xu Jiejie , Zhou Lei , Yun Xiaojing , Chen Lin , Wang Shanshan , Sun Linlin , Wen Yumei , Gu Jianxin
Published: October 2011

Of the three envelope glycoproteins encoded by hepatitis B virus (HBV) that are collectively referred to as HBV surface antigen (HBsAg), the large HBsAg (LHBs) glycoprotein is expressed preferentially in HBV-associated hepatocellular carcinoma. LHBs can act as an oncogene in transgenic mice, but how it contributes functionally to hepatocarcinogenesis remains unclear. In this study, we determined the molecular and functional roles of LHBs during HBV-associated hepatocarcinogenesis. LHBs increased tumor formation of hepatoma cells. Moreover, expression of LHBs but not other HBV envelope glycoproteins specifically promoted proliferation of hepatoma and hepatic cells in vitro. Mechanistic investigations revealed that these effects were caused by activation of the Src/PI3K/Akt pathway through proximal stimulation of PKCα/Raf1 signaling by LHBs. Proliferation induced by stable LHBs expression was associated with increased G1–S cell-cycle progression and apoptosis resistance mediated by Src kinase activation, as established in hepatocellular carcinoma clinical specimens. Importantly, LHBs-induced cellular proliferation and tumor formation were reversed by administration of the Src inhibitor saracatinib. Together, our findings suggest that LHBs promotes tumorigenesis of hepatoma cells by triggering a PKCα/Raf1 to Src/PI3K/Akt signaling pathway, revealing novel insights into the underlying mechanisms of HBV-associated hepatocarcinogenesis. Cancer Res; 71(24); 7547–57. ©2011 AACR.
A Let-7 MicroRNA SNP in the KRAS 3′UTR Is Prognostic in Early-Stage Colorectal Cancer
Authors: Smits Kim M. , Paranjape Trupti , Nallur Sunitha , Wouters Kim A.D. , Weijenberg Matty P. , Schouten Leo J. , van den Brandt Piet A. , Bosman Fred T. , Weidhaas Joanne B. , van Engeland Manon
Published: October 2011

Purpose: Colorectal cancer (CRC) is a common cause of death worldwide. Tumor-node-metastasis-system stage is currently used to guide therapy decisions but lacks precision. Prognostic biomarkers are needed to refine stratification of patients for chemotherapy but validated biomarkers are not yet available. Recently, a SNP in a lethal-7 (let-7) miRNA complementary site (LCS6) in the KRAS 3′untranslated region was suggested to affect survival in metastatic CRC. Effects in early-stage CRC are however unknown. We studied KRAS-LCS6 genotype, hypothesizing that it might identify early-stage cases with a poor prognosis, and could potentially be used in therapy decision-making.

Experimental Design: We studied 409 early stage, 182 stage III, and 69 stage IV cases, and 1,886 subcohort members from the Netherlands Cohort Study. KRAS-LCS6 genotype was assessed with TaqMan PCR. Kaplan–Meier analyses or Cox regression were used to assess associations between genotype and CRC risk or cause-specific survival.

Results: Early-stage cases with the KRAS-LCS6 variant had a lower CRC risk (incidence-rate ratio 0.68; 95% CI: 0.49–0.94) and a better survival (log-rank P = 0.038; HR 0.46; 95% CI: 0.18–1.14). In patients with KRAS-mutated CRC carrying the KRAS-LCS6 variant, the better outcome was enhanced as no patients died of CRC (log-rank P = 0.017). In advanced patients, no clear association between genotype and CRC risk or survival was observed.

Conclusions: Our results indicate that early-stage CRC cases with the KRAS-LCS6 variant have a better outcome. In advanced disease, the better outcome no longer exists. For early-stage patients, KRAS-LCS6 genotype combined with KRAS mutations merits validation as a prognostic biomarker and consideration in therapy decision-making. Clin Cancer Res; 17(24); 7723–31. ©2011 AACR.
Tumor-Associated Macrophages Promote Angiogenesis and Melanoma Growth via Adrenomedullin in a Paracrine and Autocrine Manner
Authors: Chen Peiwen , Huang Yujie , Bong Rosabel , Ding Yanping , Song Nan , Wang Xiaofeng , Song Xiaomin , Luo Yongzhang
Published: October 2011

Purpose: Elevated numbers of tumor-associated macrophages (TAM) in the tumor microenvironment are often correlated with poor prognosis in melanoma. However, the mechanisms by which TAMs modulate melanoma growth are still poorly understood. This study was aimed at examining the function and mechanism of TAM-derived adrenomedullin (ADM) in angiogenesis and melanoma growth.

Experimental Design: We established in vitro and in vivo models to investigate the relationship between TAMs and ADM in melanoma, the role and mechanism of ADM in TAM-induced angiogenesis and melanoma growth. The clinical significance of ADM and its receptors was evaluated using melanoma tissue microarrays.

Results: ADM was expressed by infiltrating TAMs in human melanoma, and its secretion from macrophages was upregulated upon coculture with melanoma cells, or with melanoma cells conditioned media. Meanwhile, TAMs enhanced endothelial cell migration and tubule formation and also increased B16/F10 tumor growth. Neutralizing ADM antibody and ADM receptor antagonist, AMA, attenuated TAM-induced angiogenesis in vitro and melanoma growth in vivo, respectively. Furthermore, ADM promoted angiogenesis and melanoma growth via both the paracrine effect, mediated by the endothelial nitric oxide synthase signaling pathway, and the autocrine effect, which stimulated the polarization of macrophages toward an alternatively activated (M2) phenotype. Finally, immunofluorescence analysis on human melanomas showed that the expression of ADM in TAMs and its receptors was greatly increased compared with adjacent normal skins.

Conclusion: Our study reveals a novel mechanism that TAMs enhance angiogenesis and melanoma growth via ADM and provides potential targets for melanoma therapies. Clin Cancer Res; 17(23); 7230–9. ©2011 AACR.
Mapping of Chromosome 1p Deletions in Myeloma Identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as Being Genes in Regions Associated with Adverse Survival
Authors: Boyd Kevin D. , Ross Fiona M. , Walker Brian A. , Wardell Christopher P. , Tapper William J. , Chiecchio Laura , Dagrada GianPaolo , Konn Zoe J. , Gregory Walter M. , Jackson Graham H. , Child J. Anthony , Davies Faith E. , Morgan Gareth J.
Published: October 2011

Purpose: Regions on 1p with recurrent deletions in presenting myeloma patients were examined with the purpose of defining the deletions and assessing their survival impact.

Experimental Design: Gene mapping, gene expression, FISH, and mutation analyses were conducted on patient samples from the MRC Myeloma IX trial and correlated with clinical outcome data.

Results: 1p32.3 was deleted in 11% of cases, and deletion was strongly associated with impaired overall survival (OS) in patients treated with autologous stem cell transplant (ASCT). In patients treated less intensively, del(1)(p32.3) was not associated with adverse progression-free survival (PFS) or OS. The target of homozygous deletions was CDKN2C, however its role in the adverse outcome of cases with hemizygous deletion was less certain. 1p22.1-21.2 was the most frequently deleted region and contained the candidate genes MTF2 and TMED5. No mutations were identified in these genes. 1p12 was deleted in 19% of cases, and deletion was associated with impaired OS in univariate analysis. The target of homozygous deletion was FAM46C, which was mutated in 3.4% of cases. When cases with FAM46C deletion or mutation were considered together, they were strongly associated with impaired OS in the intensive treatment setting.

Conclusion: Deletion of 1p32.3 and 1p12 was associated with impaired OS in myeloma patients receiving ASCT. FAM46C was identified as a gene with potential pathogenic and prognostic significance based on the occurrence of recurrent homozygous deletions and mutations. Clin Cancer Res; 17(24); 7776–84. ©2011 AACR.
The Novel Bcl-2 Inhibitor ABT-737 Is More Effective in Hypoxia and Is Able to Reverse Hypoxia-Induced Drug Resistance in Neuroblastoma Cells
Authors: Klymenko Tetyana , Brandenburg Martin , Morrow Christopher , Dive Caroline , Makin Guy
Published: October 2011

Neuroblastoma is a common solid tumor of childhood and advanced disease carries a poor prognosis despite intensive multimodality therapy. Hypoxia is a common feature of solid tumors because of poorly organized tumor-induced neovasculature. Hypoxia is associated with advanced stage and poor outcome in a range of tumor types, and leads to resistance to clinically relevant cytotoxic agents in neuroblastoma and other pediatric tumors in vitro. Resistance to apoptosis is a common feature of tumor cells and leads to pleiotropic drug resistance, mediated by Bcl-2 family proteins. ABT-737 is a novel small-molecule inhibitor of Bcl-2 and Bcl-xL that is able to induce apoptosis in a range of tumor types. Neuroblastoma cell lines are relatively resistant to ABT-737–induced apoptosis in normoxia, but in contrast to the situation with conventional cytotoxic agents are more sensitive in hypoxia. This sensitization is because of an increase in ABT-737–induced apoptosis and is variably dependent upon the presence of functional hypoxia-inducible factor 1 (HIF-1) α. In contrast to the situation in colon carcinoma and non–small cell lung cancer cells, hypoxia does not result in downregulation of the known ABT-737 resistance factor, Mcl-1, nor any other Bcl-2 family proteins. ABT-737 sensitizes neuroblastoma cells to clinically relevant cytotoxic agents under normal levels of oxygen, and importantly, this sensitization is maintained under hypoxia when neuroblastoma cells are resistant to these agents. Thus rational combinations of ABT-737 and conventional cytotoxics offer a novel approach to overcoming hypoxia-induced drug resistance in neuroblastoma. Mol Cancer Ther; 10(12); 2373–83. ©2011 AACR.
Notch Signaling Contributes to Lung Cancer Clonogenic Capacity In Vitro but May Be Circumvented in Tumorigenesis In Vivo
Authors: Osanyingbemi-Obidi Joyce , Dobromilskaya Irina , Illei Peter B. , Hann Christine L. , Rudin Charles M.
Published: October 2011

The Notch signaling pathway is a critical embryonic developmental regulatory pathway that has been implicated in oncogenesis. In non–small cell lung cancer (NSCLC), recent evidence suggests that Notch signaling may contribute to maintenance of a cancer stem or progenitor cell compartment required for tumorigenesis. We explored whether intact Notch signaling is required for NSCLC clonogenic and tumorigenic potential in vitro and in vivo using a series of genetically modified model systems. In keeping with previous observations, we find that Notch3 in particular is upregulated in human lung cancer lines and that downregulation of Notch signaling using a selective γ-secretase inhibitor (MRK-003) is associated with decreased proliferation and clonogenic capacity in vitro. We show that this phenotype is rescued with the expression of NICD3, a constitutively active cleaved form of Notch3 not affected by γ-secretase inhibition. Using an inducible LSL-KRASG12D model of lung cancer in vivo, we show a transient upregulation of Notch pathway activity in early tumor precursor lesions. However, a more rigorous test of the requirement for Notch signaling in lung oncogenesis, crossing the LSL-KRASG12D mouse model with a transgenic with a similarly inducible global dominant-negative suppressor of Notch activity, LSL-DNMAML (dominant-negative mastermind-like), reveals no evidence of Notch pathway requirement for lung tumor initiation or growth in vivo. Distinct Notch family members may have different and potentially opposing activities in oncogenesis, and targeted inhibition of individual Notch family members may be a more effective anticancer strategy than global pathway suppression. Mol Cancer Res; 9(12); 1746–54. ©2011 AACR.
Why Do Acute Ischemic Stroke Patients with a Preceding Transient Ischemic Attack Present with Less Severe Strokes? – Insights from the German Stroke Study
Authors: Weber R. , Diener H.-C. , Weimar C. ,   on behalf of the German Stroke Study Collaboration
Published: October 2011

Background: The effect of ischemic preconditioning (IP) is well established in animal models of brain ischemia. There are conflicting data from human observational studies whether IP is also induced by a preceding transient ischemic attack (TIA) resulting in a lower stroke severity in these patients. Methods: Data from 7,611 consecutive patients with first-ever acute ischemic stroke from the prospective German Stroke Study Collaboration were analyzed. A multivariate linear regression analysis was used to evaluate whether a preceding TIA was associated with a lower National Institutes of Health Stroke Scale (NIH-SS) score at admission. Furthermore, stroke severity was stratified by the latency between a preceding TIA and subsequent acute ischemic stroke (≤7 days vs. >7 days and ≤72 h vs. >72 h). Results: A previous TIA was documented in 452 (5.9%) patients, and a significantly lower NIH-SS score at admission was found in these patients compared with patients without TIA. A previous TIA remained significantly associated with a lower NIH-SS score in multivariate analysis corrected for the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, cardiovascular risk factors, age, sex and premorbid disability. The NIH-SS score at admission did not significantly differ in 96 patients with a TIA within 7 days compared with 137 patients with a TIA more than 7 days before ischemic stroke. Similarly, there were no significant differences in stroke severity in patients with a TIA within 72 h. Conclusions: The significantly lower stroke severity observed in patients with a preceding TIA is not confounded by stroke etiology in our large-scale observational study. Data on latency between the TIA and subsequent ischemic stroke do not support a neuroprotective effect caused by TIA-induced IP in human ischemic stroke.
Presence of the Metabolic Syndrome in Obese Children at Prepubertal Age
Authors: Olza J. , Gil-Campos M. , Leis R. , Bueno G. , Aguilera C.M. , Valle M. , Cañete R. , Tojo R. , Moreno L.A. , Gil A.
Published: October 2011

Background/Aims: There is a strong debate on the diagnosis and early phenotypic expression of the metabolic syndrome in children. The aim of the present study was to examine the frequency of the metabolic syndrome using various definitions in obese prepubertal and pubertal children. Methods: 478 (213 females and 265 males) obese children were recruited in three provinces of Spain. Blood pressure (BP), waist circumference, and weight and height were measured, and body mass index was calculated. Glucose, insulin, high-density lipoprotein cholesterol and triacylglycerols were determined. We classified the children according to seven different proposed definitions of the metabolic syndrome. Results: Regardless of the definition used, the prevalence of the metabolic syndrome (8.3–34.2%) was relatively high in obese children in the prepubertal period as well as in pubertal children (9.7–41.2%). We performed a principal-factor analysis to explain correlations among features of the metabolic syndrome and found that glucose metabolism (factor 1), dyslipidemia (factor 2) and obesity/BP (factor 3) explained 72% of the total variance. Conclusion: Irrespective of the classification used, the metabolic syndrome is not only present in pubertal but also in prepubertal children. International definitions of the metabolic syndrome should also consider criteria specific for children in the prepubertal period, i.e. children aged <10 years.
Phosphate Metabolism in Cardiorenal Metabolic Disease
Authors: Gupta Deepashree , Brietzke Stephen , Hayden M.R. , Kurukulasuriya L. Romayne , Sowers James R.
Published: October 2011

Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the ‘normal laboratory range’ by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease.
Chest Radiography as a Method of Screening for Occult Cancer in Patients With Idiopathic Deep Vein Thrombosis
Authors: Oliveira André Luís Cozetto de , Ribeiro Andressa , Reis Luis Fernando , Raymundo Selma Regina Soraia , Godoy José Maria Pereira de
Published: October 2011

The occurrence of neoplasms in patients with idiopathic deep vein thrombosis (DVT) may result in a significant reduction in survival rates. The aim of our study was to assess the use of chest X-rays (CXRs) as a screening method of intrathoracic neoplasms in patients who with idiopathic DVT. In observational, cross-sectional study, the medical records of 99 patients with idiopathic DVT, who were submitted to CXR (during the hospital stay or within 30 days after discharge), were investigated. Of these patients, 15.1% had images suggestive of thoracic neoplasias (single or multiple pulmonary nodules and mediastinal widening). Neoplasms were diagnosed in 4 patients in the follow-up with CXR. The CXR is an option of early screening for thoracic neoplasms and other nonmalignant diseases in patients with idiopathic DVT.
Clinical Features of Early Myocardial Rupture of Acute Myocardial Infarction
Authors: Suzuki Makoto , Enomoto Daijiro , Seike Fumiyasu , Fujita Shimpei , Honda Kazuo
Published: October 2011

We assessed the clinical features of patients with myocardial rupture within 48 to 72 hours, defined as early myocardial rupture, after percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI). Six patients (4 men, 66 ± 13 years) with early myocardial rupture were identified from 1252 consecutive patients undergoing PCI for STEMI. We evaluated the degree of microvascular reperfusion using thrombolysis in myocardial infarction (TIMI) myocardial perfusion (TMP) grade and a resolution of sum of ST-segment elevation in a 12-lead electrocardiogram (ECG). Time from PCI to myocardial rupture was 11 ± 7 hours. All patients showed TMP grade 0 or 1 and an increase in sum of ST-segment elevation after PCI (1.9 ± 0.5 vs 2.5 ± 0.7 mV; P = .032), suggesting severely failed reperfusion at the level of microcirculation as the common feature to develop early myocardial rupture after PCI for STEMI.
Assessment and Treatment of Gastroesophageal Reflux in Healthy Infants With Apneic Episodes
Authors: Koivusalo Antti I. , Pakarinen Mikko P. , Wikström Anne , Rintala Risto J.
Published: October 2011

This retrospective study sought to assess whether gastroesophageal reflux (GER) is associated with recurrent infant apneic episodes (AEs) and whether its treatment prevents AEs. Symptoms, diagnostic measures, and treatment of GER in 87 infants admitted for AEs were recorded. The effect of GER on recurrent AEs and survival were assessed. Esophageal pH monitoring was done to 58/87 (67%) patients, of whom 53/58 (91%) had a pathological finding; 48 patients had treatment for GER (medical 43%/49%; surgical 5%/6%) with continuing AEs during hospitalization (25%/29% patients) as the main indication. Follow-up (65 patients) disclosed recurrent AEs in 12 (18%) patients (no treatment 4/21, medical 8/39, surgical 0/5, P = NS). All 87 patients survived. Recurrent AEs after discharge was predicted by AEs during hospitalization but not by pathological GER. AEs observed during hospitalization predicted postdischarge AE recurrence. Of GER treatment modalities, only surgery prevented recurrent AEs.
Social Anxiety, Motivation, Self-Disclosure, and Computer-Mediated Friendship
Authors: Tian Qing
Published: October 2011

This study aims to investigate the mechanisms of individuals’ social interaction with new and existing friends in the blogosphere. It examines not only the direct association between social anxiety and online friendships but also the mediating effects of motivation and self-disclosure on the relation through path analysis. A total of 385 bloggers recruited online responded to the survey questionnaire. The results showed that compared with low socially anxious individuals, those with high social anxiety tended to make fewer new friends, communicated with fewer existing friends via blogs, and had lower relationship quality with those existing friends, but had higher relationship quality with new friends made through blogs. With regard to mediation, the higher the bloggers’ social anxiety, the more motivated they were to make new friends via blogs and the more intimate information they disclosed on their blogs, both of which were, in turn, associated with more new friends and higher quality of new friendships. Interpretations of the findings and implications for understanding the social use of the Internet, especially the competing social compensation hypothesis and rich-get-richer hypothesis, are discussed.
Charitable Collaborations in Bronzeville, 1928-1944
Authors: Semmes Clovis E.
Published: October 2011

In the twentieth century, race-based residential and commercial segregation that supported racial oppression and inequality became an elemental characteristic of urban black communities. Conflict-ridden, black-white relationships were common. However, the Chicago Defender Charities, Inc., the entity that sponsors the largest African American parade in the country and that emerged in 1947, embodied a tradition of charitable giving, self-help, and community service initiated in 1921 by Chicago Defender newspaper founder and editor, Robert S. Abbott. The foundation of this charitable tradition matured as a result of an early and sustained collaboration between Chicago’s white-owned Regal Theater and the black-owned Chicago Defender newspaper. Thus, in segregated African American communities, black and white commercial institutions, under certain conditions, were able to find important points of collaboration to uplift the African American communities of which they were a part.
Knowledge management and innovation performance in a high-tech SMEs industry
Authors: Alegre Joaquín , Sengupta Kishore , Lapiedra Rafael
Published: October 2011

This article examines how knowledge management (KM) affects innovation performance within biotechnology firms. This is an industry in which small- and medium-sized biotech enterprises live together with the biotech divisions of large pharmaceutical firms. We conceptualize KM as a set of practices and dynamic capabilities, and hypothesize that KM dynamic capabilities act as a mediating variable between KM practices and innovation performance. We use structural equation modelling to test the hypotheses on a data set from the biotechnology industry. The results support our conceptualization and demonstrate its utility in explaining differences in innovation performance across firms. Findings have important implications regarding KM and innovation in high-tech small- and medium-sized enterprises.
Plasma levels of potassium and magnessium after modified ultrafiltration in pediatric cardiac surgery with cardiopulmonary bypass
Authors: López R , Lema G , González A , Carvajal C , Canessa R , Carrasco P , Lazo V , Hudson C , Gonzalez R , Frangini P
Published: October 2011

Objective: Modified ultrafiltration (MUF) reduces some of the complications associated with cardiopulmonary bypass (CPB) in pediatric cardiac surgery. However, we have observed hypokalemia and hypomagnesemia in children when MUF is used. Such alterations may elicit severe arrhythmias in the postoperative period. To date, no studies have focused on the effects MUF may have in plasma levels of potassium (K) and magnesium (Mg). The objective of our study was to determine if there is any variation in plasma levels of K (plK) and Mg (plMg) after MUF in children undergoing cardiac surgery with CPB.

Patients: Sixteen children scheduled for cardiac surgery with CBP and MUF were prospectively studied. Anesthetic, CPB and MUF management were standardized for all patients, the latter lasting for 10 minutes.

Results: Plasma K average levels before and after MUF were 4.16 mmol/L and 3.58 mmol/L, respectively. The average plasma Mg levels before and after MUF were 4.82 mmol/L and 4.81 mmol/L, respectively.

Conclusions: The plasma level of K is reduced by 13.7% after MUF (p<0.0001). The reduction in Mg at the same period of time was not statistically significant (p<0.970).
Systematic Review and Empirical Comparison of Contemporaneous EQ-5D and SF-6D Group Mean Scores
Authors: Whitehurst David G. T. , Bryan Stirling , Lewis Martyn
Published: October 2011

Background. Group mean estimates and their underlying distributions are the focus of assessment for cost and outcome variables in economic evaluation. Research focusing on the comparability of alternative preference-based measures of health-related quality of life has typically focused on analysis of individual-level data within specific clinical specialties or community-based samples. Purpose. To explore the relationship between group mean scores for the EQ-5D and SF-6D across the utility scoring range. Methods. Studies were identified via a systematic search of 13 online electronic databases, a review of reference lists of included papers, and hand searches of key journals. Studies were included if they reported contemporaneous mean EQ-5D and SF-6D health state scores. All (sub)group comparisons of group mean EQ-5D and SF-6D scores identifiable from text, tables, or figures were extracted from identified studies. A total of 921 group mean comparisons were extracted from 56 studies. The nature of the relationship between the paired scores was examined using ranked scatter graphs and analysis of agreement. Results. Systematic differences in group mean estimates were observed at both ends of the utility scale. At the lower (upper) end of the scale, the SF-6D (EQ-5D) provides higher mean utility estimates. Conclusions. These findings show that group mean EQ-5D and SF-6D scores are not directly comparable. This raises serious concerns about the cross-study comparability of economic evaluations that differ in the choice of preference-based measures, although the review focuses on 2 of the available instruments only. Further work is needed to address the practical implications of noninterchangeable utility estimates for cost-per-QALY estimates and decision making.
Burning behavior of wood-plastic composite decking boards in end-use conditions: the effects of geometry, material composition, and moisture
Authors: Seefeldt Henrik , Braun Ulrike
Published: October 2011

In this study, we investigated the basic knowledge necessary to develop flame-retarded wood–plastic composite (WPC) materials by focusing on decking boards. Therefore, the respective effects of geometry, material composition, and moisture were studied by performing cone calorimetric measurements. Using hollow-shaped geometries removes combustible material and reduces the fire load but simultaneously increases fire propagation. The best results were achieved by using high-wood contents. The addition of talc can reduce the intensity of burning. Moisture also has a positive effect on burning behavior. Apart from the well-known mechanism of water, a change was observed in the resultant residue.
Psychological Profile of Male and Female Animal Abusers
Authors: Schwartz Rebecca L. , Fremouw William , Schenk Allison , Ragatz Laurie L.
Published: October 2011

This study had three purposes: to explore psychological characteristics of animal abusers (criminal thinking styles, empathy, and personality traits), to replicate previously reported results (past illegal actions, bullying behavior), and to examine potential gender differences. The self-reported animal abuser group was 29 college students who reported two or more incidents of animal abuse; controls were 29 college students matched on age and gender. Participants completed self-report measures of criminal thinking, illegal behaviors, bullying, empathy, and the five-factor personality traits. Results indicated animal abusers had more previous criminal behaviors, were more likely to bully, and had the highest scores on the power orientation criminal thinking scale. Abuser by gender interactions were detected; female animal abusers scored significantly higher on several measures of criminal thinking, were found to be more likely to bully, and exhibited lower scores on measures of perspective taking and empathy compared to female controls.
Applications of instrumented indentation testing for the characterization of polypropylene materials
Authors: Koch T , Seidler S
Published: October 2011

In this study, instrumented indentation testing, or so-called depth-sensing indentation testing, was used to characterize polypropylene (PP) materials. The influence of molecular weight and cooling rate on the hardness was investigated showing that low cooling rates and relatively low molecular weight lead to higher hardness values. In random copolymers of propene with butene and hexene, the correlation between hardness and degree of crystallinity is linear and the conversion to the amorphous state could be detected. Blends of PP with ethylene–propylene elastomer show a strong negative deviation of indentation modulus from linear rule of mixture. This behaviour can be described by Kerner’s model in the case of particulate arrangement and by Davies’ model in the phase inversion region. The addition of high-density polyethylene to PP results in a synergistic behaviour of modulus which can be attributed to nucleation effects.

Furthermore, the application of indentation testing to detect physical ageing of a surface of an injection-moulded specimen and heterogeneity of weld lines was shown. Orientations in a biaxially oriented film could be detected using Knoop indenter.