bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Determination of Moisture in Powder Milk Using Near Infrared Spectroscopy
Authors: Nagarajan R. , Singh Parul , Mehrotra Ranjana
Published: August 2006

Moisture content in commercially available milk powder was investigated using near infrared (NIR) diffuse reflectance spectroscopy with an Indian low‐cost dispersive NIR spectrophotometer. Different packets of milk powder of the same batch were procured from the market. Forty‐five samples with moisture range 4–10% were prepared in the laboratory. Spectra of the samples were collected in the wavelength region 800–2500 nm. Moisture values of all the samples were simultaneously determined by Karl Fischer (KF) titration. These KF values were used as reference for developing calibration model using partial least squares regression (PLSR) method. The calibration and validation statistics are , RMSEC : 0.1040, and ,
RMSEV : 0.1730. Five samples of unknown moisture contents
were taken for NIR prediction using developed calibration model.
The agreement between NIR predicted results and those of Karl
Fischer values is appreciable. The result shows that the
instrument can be successfully used for the determination of
moisture content in milk powder.
Hypothesis: A Role for Fragile X Mental Retardation Protein in Mediating and Relieving MicroRNA‐Guided Translational Repression?
Authors: Plante Isabelle , Provost Patrick
Published: August 2006

MicroRNA (miRNA)‐guided messenger RNA (mRNA) translational repression is believed to be mediated by effector miRNA‐containing ribonucleoprotein (miRNP) complexes harboring fragile X mental retardation protein (FMRP). Recent studies documented the nucleic acid chaperone properties of FMRP and characterized its role and importance in RNA silencing in mammalian cells. We propose a model in which FMRP could facilitate miRNA assembly on target mRNAs in a process involving recognition of G quartet structures. Functioning within a duplex miRNP, FMRP may also mediate mRNA targeting through a strand exchange mechanism, in which the miRNA* of the duplex is swapped for the mRNA. Furthermore, FMRP may contribute to the relief of miRNA‐guided mRNA repression through a reverse strand exchange reaction, possibly initiated by a specific cellular signal, that would liberate the mRNA for translation. Suboptimal utilization of miRNAs may thus account for some of themolecular defects in patients with the fragile X syndrome.
Roles of Cholesterol and Lipids in the Etiopathogenesis ofAlzheimer′s Disease
Authors: Rojo Leonel , Sjöberg Marcela K. , Hernández Paula , Zambrano Cristian , Maccioni Ricardo B.
Published: August 2006

Alzheimer′s disease is the principal cause of dementia throughout
the world and the fourth cause of death in developed
economies.This brain disorder is characterized by the formation of
brain protein aggregates, namely, the paired helical filaments and
senile plaques. Oxidative stress during life, neuroinflamamtion,
and alterations in neuron‐glia interaction patterns have been also
involved in the etiopathogenesis of this disease. In recent years,
cumulative evidence has been gained on the involvement of
alteration in neuronal lipoproteins activity, as well as on the
role of cholesterol and other lipids in the pathogenesis of this
neurodegenerative disorder. In this review, we analyze the links
between changes in cholesterol homeostasis, and the changes of
lipids of major importance for neuronal activity and
Alheimer′s disease. The investigation on the fine molecular
mechanisms underlying the lipids influence in the etiopathogenesis
of Alzheimer′s disease may shed light into its treatment and
medical management.
Damping Augmentation of Nanocomposites Using Carbon Nanofiber Paper
Authors: Gou Jihua , O′Braint Scott , Gu Haichang , Song Gangbing
Published: August 2006

Vacuum‐assisted resin transfer molding (VARTM) process was used to fabricate the nanocomposites through integrating carbon nanofiber paper into traditional glass fiber reinforced composites. The carbon nanofiber paper had a porous structure with highly entangled carbon nanofibers and short glass fibers. In this study, the carbon nanofiber paper was employed as an interlayer and surface layer of composite laminates to enhance the damping properties. Experiments conducted using the nanocomposite beam indicated up to 200–700% increase of the damping ratios at higher frequencies. The scanning electron microscopy (SEM) characterization of the carbon nanofiber paper and the nanocomposites was also conducted to investigate the impregnation of carbon nanofiber paper by the resin during the VARTM process and the mechanics of damping augmentation. The study showed a complete penetration of the resin through the carbon nanofiber paper. The connectivities between carbon nanofibers and short glass fibers within the carbon nanofiber paper were responsible for the significant energy dissipation in the nanocomposites during the damping tests.
Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-α(PPARα)
Authors: Tien Eric S. , Hannon Daniel B. , Thompson Jerry T. , Vanden Heuvel John P.
Published: August 2006

The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-α(PPARα) was examined. PPAR-binding protein (PBP), PPARγcoactivator-1α(PGC-1α), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPARαactivity in the presence of Wy-14,643. The effects on PPARαactivity in light of increased or decreased expression of these coactivators were qualitatively different depending on the ligand examined. Diminished expression of PGC-1α, SRC-1, or PBP by RNAi plasmids affected natural or synthetic agonist activity whereas only Wy-14,643 was affected by decreased PGC-1α. The interaction of PPARαwith an LXXLL-containing peptide library showed ligand-specific patterns, indicative of differences in conformational change. The association of coactivators to PPARαoccurs predominantly via the carboxyl-terminus and mutating456LHPLL to456LHPAA resulted in a dominant-negative construct. This research confirms that coactivator recruitment to PPARαis ligand-dependent and that selective receptor modulators (SRMs) of this important protein are likely.
The Aurora Kinase Inhibitor VX-680 Induces Endoreduplication and Apoptosis Preferentially in Cells with Compromised p53-Dependent Postmitotic Checkpoint Function
Authors: Gizatullin Farid , Yao Yao , Kung Victor , Harding Matthew W. , Loda Massimo , Shapiro Geoffrey I.
Published: August 2006

VX-680 is a potent inhibitor of Aurora kinases that induces the accumulation of cells with ≥4N DNA content, followed by cell death. Here, we define the role of p53 and p21Waf1/Cip1 in cell cycle perturbations following exposure to VX-680. Endoreduplication and apoptosis in response to VX-680 are limited in A549 and MCF-7 cells expressing wild-type p53, and markedly enhanced in cells lacking p53, including those engineered to express the HPV16-E6 oncoprotein or short interfering RNA pools targeting p53. In contrast, endoreduplication and apoptosis occur in the p53 wild-type cell lines, RKO and U2OS. The difference in response to VX-680 among these cell lines correlates with the timing of induction of p21Waf1/Cip1 and its ability to inhibit cyclin E-cdk2 activity. In A549 cells, VX-680 induces the expression of p53 and p21Waf1/Cip1 within 24 hours, with consequent inhibition of cyclin E-cdk2, and reduction of retinoblastoma protein phosphorylation, limiting endoreduplication. In RKO and U2OS cells, the induction of p21Waf1/Cip1 is delayed and associated with higher residual cyclin E-cdk2 kinase activity and retinoblastoma protein phosphorylation, followed by progressive endoreduplication and apoptosis. Abrogation of p21Waf1/Cip1 expression by short interfering RNA targeting in A549 cells results in a substantial increase in the degree of endoreduplication, whereas inducible expression of p21Waf1/Cip1 in p53-negative NCI-H1299 cells inhibits VX-680-induced endoreduplication and cell death. These data suggest that the integrity of the p53-p21Waf1/Cip1–dependent postmitotic checkpoint governs the response to Aurora kinase inhibition. Although cells with intact checkpoint function arrest with 4N DNA content, those with compromised checkpoint function are more likely to undergo endoreduplication followed by eventual apoptosis. (Cancer Res 2006; 66(15): 7668-77)
15-Hydroxyprostaglandin Dehydrogenase Is a Tumor Suppressor of Human Breast Cancer
Authors: Wolf Ido , O'Kelly James , Rubinek Tamar , Tong Min , Nguyen Anh , Lin Bryan T. , Tai Hsin-Hsiung , Karlan Beth Y. , Koeffler H. Phillip
Published: August 2006

Prostaglandin E2 plays a growth-stimulatory role in breast cancer, and the rate-limiting enzyme in its synthesis, cyclooxygenase-2, is often overexpressed in these cancers. Little is known about the role of the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in breast cancer pathogenesis. Using a pharmacologically based screen for epigenetically silenced genes, we found low levels of 15-PGDH in MDA-MB-231 cells [estrogen receptor (ER) negative] but high levels in MCF-7 cells (ER positive) and observed its up-regulation following demethylation treatment. Further analysis revealed methylation of the 15-PGDH promoter in one breast cancer cell line and 30% of primary tumors. Analysis of 15-PGDH expression revealed low levels in 40% of primary breast tumors and identified a correlation between 15-PGDH and ER expression. Transfection assays showed that transient up-regulation of 15-PGDH levels in MDA-MB-231 cells resulted in a decreased clonal growth, and stable up-regulation significantly decreased the ability of these cells to form tumors in athymic mice. In contrast, transient silencing of 15-PGDH in MCF-7 cells resulted in their enhanced proliferation, and a stable silencing in these cells enhanced cell cycle entry in vitro and tumorigenicity in vivo. Forced expression of 15-PGDH inhibited the ER pathway and silencing of 15-PGDH up-regulated expression of aromatase. In addition, 15-PGDH levels were down-regulated by estrogen but up-regulated by the tumor suppressor gene CAAT/enhancer binding protein α. Our results indicate for the first time that 15-PGDH may be a novel tumor suppressor gene in breast cancer, and suggest that this enzyme can modulate the ER pathway. (Cancer Res 2006; 66(15): 7818-23)
Selection of Tumor-binding Ligands in Cancer Patients with Phage Display Libraries
Authors: Krag David N. , Shukla Girja S. , Shen Guang-Ping , Pero Stephanie , Ashikaga Taka , Fuller Susan , Weaver Donald L. , Burdette-Radoux Susan , Thomas Christian
Published: August 2006

Phage display has been used extensively in vitro and in animal models to generate ligands and to identify cancer-relevant targets. We report here the use of phage-display libraries in cancer patients to identify tumor-targeting ligands. Eight patients with stage IV cancer, including breast, melanoma, and pancreas, had phage-displayed random peptide or scFv library (1.6 × 108-1 × 1011 transducing units/kg) administered i.v.; tumors were excised after 30 minutes; and tumor-homing phage were recovered. In three patients, repeat panning was possible using phage recovered and amplified from that same patient's tumor. No serious side effects, including allergic reactions, were observed with up to three infusions. Patients developed antiphage antibodies that reached a submaximal level within the 10-day protocol window for serial phage administration. Tumor phage were recoverable from all the patients. Using a filter-based ELISA, several clones from a subset of the patients were identified that bound to a tumor from the same patient in which clones were recovered. The clone-binding to tumor was confirmed by immunostaining, bioassay, and real-time PCR–based methods. Binding studies with noncancer and cancer cell lines of the same histology showed specificity of the tumor-binding clones. Analysis of insert sequences of tumor-homing peptide clones showed several motifs, indicating nonrandom accumulation of clones in human tumors. This is the first reported series of cancer patients to receive phage library for serial panning of tumor targeting ligands. The lack of toxicity and the ability to recover clones with favorable characteristics are a first step for further research with this technology in cancer patients. (Cancer Res 2006; 66(15): 7724-33)
Targeted Therapy with aSalmonella TyphimuriumLeucine-Arginine Auxotroph Cures Orthotopic Human Breast Tumors in Nude Mice
Authors: Zhao Ming , Yang Meng , Ma Huaiyu , Li Xiaoming , Tan Xiuying , Li Shukuan , Yang Zhijian , Hoffman Robert M.
Published: August 2006

We report here a modified auxotrophic strain of Salmonella typhimurium that can target and cure breast tumors in orthotopic mouse models. We have previously reported development of a genetically modified strain of S. typhimurium, selected for prostate tumor targeting and therapy in vivo. The strain, termed S. typhimurium A1, selectively grew in prostate tumors in xenograft models causing tumor regression. In contrast, normal tissue was cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. A1 is auxotrophic (leucine-arginine dependent) but apparently receives sufficient nutritional support only from tumor tissue. The ability to grow in viable tumor tissue may account, in part, for the unique antitumor efficacy of the strain. In the present report, to increase tumor-targeting capability of A1, the strain was reisolated after infection of a human colon tumor growing in nude mice. The tumor-isolated strain, termed A1-R, had increased targeting for tumor cells in vivo as well as in vitro compared with A1. Treatment with A1-R resulted in highly effective tumor targeting, including viable tumor tissue and significant tumor shrinkage in mice with s.c. or orthotopic human breast cancer xerographs. Survival of the treated animals was significantly prolonged. Forty percent of treated mice were cured completely and survived as long as non–tumor-bearing mice. These results suggest that amino acid auxotrophic virulent bacteria, which selectively infect and attack viable tumor tissue, are a promising approach to cancer therapy. (Cancer Res 2006; 66(15): 7647-52)
Impaired Notch Signaling Promotes De novo Squamous Cell Carcinoma Formation
Authors: Proweller Aaron , Tu Lili , Lepore John J. , Cheng Lan , Lu Min Min , Seykora John , Millar Sarah E. , Pear Warren S. , Parmacek Michael S.
Published: August 2006

Signaling through Notch receptors in the skin has been implicated in the differentiation, proliferation, and survival of keratinocytes, as well as in the pathogenesis of basal cell carcinoma (BCC). To determine the composite function of Notch receptor–mediated signaling in the skin and overcome potential redundancies between receptors, conditional transgenic mice were generated that express the pan-Notch inhibitor, dominant-negative Mastermind Like 1 (DNMAML1), to repress all canonical [CBF-1/Suppressor of hairless/LAG-1 (CSL)–dependent] Notch signaling exclusively in the epidermis. Here, we report that DNMAML1 mice display hyperplastic epidermis and spontaneously develop cutaneous squamous cell carcinoma (SCC) as well as dysplastic precursor lesions, actinic keratoses. Mice expressing epidermal DNMAML1 display enhanced accumulation of nuclear β-catenin and cyclin D1 in suprabasilar keratinocytes and in lesional cells from SCCs, which was also observed in human cutaneous SCC. These results suggest a model wherein CSL-dependent Notch signaling confers protection against cutaneous SCC. The demonstration that inhibition of canonical Notch signaling in mice leads to spontaneous formation of SCC and recapitulates the disease in humans yields fundamental insights into the pathogenesis of SCC and provides a unique in vivo animal model to examine the pathobiology of cutaneous SCC and for evaluating novel therapies. (Cancer Res 2006; 66(15): 7438-44)
Ifosfamide-Induced Nephrotoxicity: Mechanism and Prevention
Authors: Nissim Itzhak , Horyn Oksana , Daikhin Yevgeny , Nissim Ilana , Luhovyy Bohdan , Phillips Peter C. , Yudkoff Marc
Published: August 2006

The efficacy of ifosfamide (IFO), an antineoplastic drug, is severely limited by a high incidence of nephrotoxicity of unknown etiology. We hypothesized that inhibition of complex I (C-I) by chloroacetaldehyde (CAA), a metabolite of IFO, is the chief cause of nephrotoxicity, and that agmatine (AGM), which we found to augment mitochondrial oxidative phosphorylation and β-oxidation, would prevent nephrotoxicity. Our model system was isolated mitochondria obtained from the kidney cortex of rats treated with IFO or IFO + AGM. Oxidative phosphorylation was determined with electron donors specific to complexes I, II, III, or IV (C-I, C-II, C-III, or C-IV, respectively). A parallel study was done with 13C-labeled pyruvate to assess metabolic dysfunction. Ifosfamide treatment significantly inhibited oxidative phosphorylation with only C-I substrates. Inhibition of C-I was associated with a significant elevation of [NADH], depletion of [NAD], and decreased flux through pyruvate dehydrogenase and the TCA cycle. However, administration of AGM with IFO increased [cyclic AMP (cAMP)] and prevented IFO-induced inhibition of C-I. In vitro studies with various metabolites of IFO showed that only CAA inhibited C-I, even with supplementation with 2-mercaptoethane sulfonic acid. Following IFO treatment daily for 5 days with 50 mg/kg, the level of CAA in the renal cortex was ∼15 μmol/L. Taken together, these observations support the hypothesis that CAA is accumulated in renal cortex and is responsible for nephrotoxicity. AGM may be protective by increasing tissue [cAMP], which phosphorylates NADH:oxidoreductase. The current findings may have an important implication for the prevention of IFO-induced nephrotoxicity and/or mitochondrial diseases secondary to defective C-I. (Cancer Res 2006; 66(15): 7824-31)
Real-time Evaluation of p53 Oscillatory Behavior In vivo Using Bioluminescent Imaging
Authors: Hamstra Daniel A. , Bhojani Mahaveer S. , Griffin Laura B. , Laxman Bharathi , Ross Brian D. , Rehemtulla Alnawaz
Published: August 2006

p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo. (Cancer Res 2006; 66(15): 7482-9)
Platelet Activation by Low Density Lipoprotein and High Density Lipoprotein
Authors: Korporaal Suzanne J.A. , Akkerman Jan-Willem N.
Published: August 2006

Cardiovascular disease is the main cause of death and disability in the Western society. Lipoproteins are important in the development of cardiovascular disease since they change the properties of different cells involved in atherosclerosis and thrombosis. The interaction of platelets with lipoproteins has been under intense investigation. Particularly the initiation of platelet signaling pathways by low density lipoprotein (LDL) has been studied thoroughly, since platelets of hypercholesterolemic patients, whose plasma contains elevated LDL levels due to absent or defective LDL receptors, show hyperaggregability in vitro and enhanced activity in vivo. These observations suggest that LDL enhances platelet responsiveness. Several signaling pathways induced by LDL have been revealed in vitro, such as signaling via p38 mitogen-activated protein kinase and p125 focal adhesion kinase. High density lipoprotein (HDL) consists of two subtypes, HDL2 and HDL3, which have opposing effects on platelet activation. This review provides a summary of the activation of signaling pathways after platelet-LDL and platelet-HDL interaction, with special emphasis on their role in the development of thrombosis and atherosclerosis.
Platelet Interaction with Bioactive Lipids Formed by Mild Oxidation of Low-Density Lipoprotein
Authors: Siess Wolfgang
Published: August 2006

Oxidation of low-density lipoprotein (LDL) generates pro-inflammatory and pro-thrombotic mediators that play a crucial role in cardiovascular and inflammatory diseases. Mildly oxidized LDL (mox-LDL) and minimally modified LDL (mm-LDL) which escape the uptake of macrophage scavenger receptors accumulate in the atherosclerotic intima. Oxidatively modified LDL is also present within the electronegative LDL fraction in blood, which is elevated in patients at high risk for cardiovascular diseases. Mox-LDL and mm-LDL, but not native LDL are able to induce platelet shape change and aggregation. LDL oxidation generates lipids with platelet stimulatory properties such as lysophosphatidylcholine, certain oxidized phosphatidylcholine molecules, F2-isoprostanes and lysophosphatidic acid (LPA). Mox-LDL and mm-LDL are like a Trojan horse carrying these biologically active lipids and attacking cells through activation of physiological receptors and signaling mechanisms. LPA has been identified as the lipid responsible for platelet stimulation by mox-LDL, mm-LDL and also mox-HDL. These lipoproteins activate platelets by stimulating G-protein coupled LPA receptors and a Rho/Rho kinase signaling pathway leading to platelet shape change and subsequent aggregation. LPA-mediated platelet activation might contribute to arterial thrombus formation after rupture of atherosclerotic plaques and to the increased blood thrombogenicity of patients with cardiovascular diseases.
Low-Density Lipoprotein-Lowering Medication and Platelet Function
Authors: Ferroni Patrizia , Basili Stefania , Santilli Francesca , Davì Giovanni
Published: August 2006

Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) levels represent one of the most important risk factors for atherosclerosis and therefore cardiovascular morbidity and mortality. LDL-C operates at different levels and through various classic and non-classic mechanisms. In particular, increased or modified LDL enhances platelet function and increases sensitivity of platelets to several naturally occurring agonists. Agents that lower LDL-C in hypercholesterolemic patients have been shown to interfere with platelet function. Several studies, in fact, suggested that statins exert anti-thrombotic effects largely as a result of an anti-platelet activity. Among the other LDL-C-lowering agents those acting by interfering with cholesterol reabsorption from the gut (cholestyramine, colestipol) do not appear to interfere with platelet function, whereas peroxisome proliferator-activated receptor agonists (such as fibrates) can inhibit platelet function. The full potential of these drugs in vascular protection is only just being realized. Further studies are still needed to elucidate the full therapeutic benefits of these agents in plaque stabilization and thrombosis.
Aortic Stiffness Is an Independent Determinant of B-Type Natriuretic Peptide in Patients with Coronary Artery Disease
Authors: Sakuragi Satoru , Okawa Keisuke , Iwasaki Jun , Tokunaga Naoto , Kakishita Mikio , Ohe Toru
Published: August 2006

Previous studies demonstrated that the B-type natriuretic peptide (BNP) level is high in some patients with coronary artery disease (CAD) despite a preserved left ventricular function, although the mechanism underlying this increase in patients with CAD has not been fully elucidated. Because aortic stiffness is greater in patients with CAD and increases with CAD severity, there is a possibility that an increased aortic stiffness in turn increases the elevation of the BNP level in patients with CAD. In this study, we measured BNP level and brachial-ankle pulse wave velocity (baPWV) in 134 patients with CAD, and evaluated the relationship between BNP and baPWV. The patients were classified on the basis of the quartiles of BNP level to identify the characteristics of patients with a high BNP level. baPWV was significantly greater in patients classified into the highest quartile of BNP level than in those classified into the other quartiles. Multivariate analysis demonstrated that baPWV and left ventricular ejection fraction independently correlated with BNP level. Logistic regression analysis demonstrated that the odds ratio for the highest quartile of BNP level increased with baPWV quartile. This association remained significant after adjustment for systolic and diastolic function. In conclusion, increased aortic stiffness possibly underlies the increase in the BNP level in patients with CAD.
Finger Length Ratio (2D:4D) and Dimensions of Sexual Orientation
Authors: Kraemer Bernd , Noll Thomas , Delsignore Aba , Milos Gabriella , Schnyder Ulrich , Hepp Urs
Published: August 2006

Background: It has been suggested that both adult sexual orientation and the 2nd to 4th finger length ratio (2D:4D) are influenced by prenatal testosterone levels. Bearing this in mind, 2D:4D has been tested as a proxy measure of the putative prenatal testosterone impact on adult human homosexuality, but the results are inconsistent. To date, most studies in this field of research comprise categorical group comparison of heterosexuals and homosexuals with respect to their 2D:4D. Aims: The purpose of our study was to evaluate 2D:4D and the dimensional perspective of sexual orientation in addition to categorical results. Methods: We examined a community-based sample of 409 subjects and calculated correlations of 2D:4D and sexual orientation as a continuum ranging from homosexual to heterosexual. Results: We found a significant negative correlation of 2D:4D with homosexual orientation (fantasy, attraction, activity and general score) in women, but not in men. Conclusions: Our results indicate that with higher prenatal testosterone levels in women, the likelihood of homosexual orientation might increase. We hypothesize a continuous neurohormonal sexual differentiation of the brain, most notably for women, that overrides categories and results in varying dimensions of sexual orientation. This hypothesis contrasts with the predominant suggestion of fixed organizational effects of androgens in the brain and a categorical sexual orientation.
Usefulness of MRI to Demonstrate the Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy with Myocardial Bridge
Authors: Thomson Vivien , Botnar Rene , Croisille Pierre
Published: August 2006

We present a case of symptomatic primary hypertrophic cardiomyopathy (HCM) associated with myocardial bridging of the left anterior descending (LAD) artery and suspected ischemia that could be related either to LAD artery compression or to microvascular perfusion abnormalities. MRI demonstrated the morphological appearance of myocardial hypertrophy, and coronary MR angiography evidenced the myocardial bridge and its functional consequences with stress MR perfusion. In conclusion, as a non-invasive comprehensive imaging technique, MRI should be considered in identifying the mechanisms of myocardial ischemia in HCM with myocardial bridge.
A Fast, Unbiased and Exact Allelic Test for Case-Control Association Studies
Authors: Guedj M. , Wojcik J. , Della-Chiesa E. , Nuel G. , Forner K.
Published: August 2006

Association studies are traditionally performed in the case-control framework. As a first step in the analysis process, comparing allele frequencies using the Pearson’s chi-square statistic is often invoked. However such an approach assumes the independence of alleles under the hypothesis of no association, which may not always be the case. Consequently this method introduces a bias that deviates the expected type I error-rate. In this article we first propose an unbiased and exact test as an alternative to the biased allelic test. Available data require to perform thousands of such tests so we focused on its fast execution. Since the biased allelic test is still widely used in the community, we illustrate its pitfalls in the context of genome-wide association studies and particularly in the case of low-level tests. Finally, we compare the unbiased and exact test with the Cochran-Armitage test for trend and show it perfoms similarly in terms of power. The fast, unbiased and exact allelic test code is available in R, C++ and Perl at: http://stat.genopole.cnrs.fr/software/fueatest.
Heritability of Serum Iron, Ferritin and Transferrin Saturation in a Genetically Isolated Population, the Erasmus Rucphen Family (ERF) Study
Authors: Njajou O.T. , Alizadeh B.Z. , Aulchenko Y. , Zillikens M.C. , Pols H.A.P. , Oostra B.A. , Swinkels D.W. , van Duijn C.M.
Published: August 2006

Background: Iron has been implicated in the pathogenesis of various disorders. Mutations in the HFE gene are associated with an increase in serum iron parameters. The aim of this study was to estimate the heritability in serum iron parameters explained by HFE. Methods: Ninety families (980 subjects) were included in the present analysis. Heritability estimation was conducted using the variance component method. The likelihood ratio test was used to compare models. Phenotypic and genetic correlations between serum iron parameters were calculated. Results: The heritability (h2 ± SE) estimates were 0.23 ± 0.07 (p < 0.0001) for iron, 0.29 ± 0.09 (p < 0.0001) for ferritin and 0.28 ± 0.07 (p < 0.0001) for transferrin saturation while adjusting for age, age2 and sex. The HFE genotypes explained between 2 to 6% of the sex and age-adjusted variance in serum iron, ferritin and transferrin saturation. There was a high genetic correlation between serum iron parameters, suggesting pleiotropy between these traits. Conclusion: A substantial proportion of the variance of iron, ferritin and transferrin saturation can be explained by additive genetic effects, independent of sex and age. The HFE genotypes explained a considerable proportion of serum iron parameters and may be an important factor in the complex iron network.
Comparison of Women’s Diet Assessed by FFQs and 24-Hour Recalls with and without Underreporters: Associations with Biomarkers
Authors: Olafsdottir Anna S. , Thorsdottir Inga , Gunnarsdottir Ingibjörg , Thorgeirsdottir Holmfridur , Steingrimsdottir Laufey
Published: August 2006

Background/Aims: Women’s diet can be especially difficult to assess, as women tend to underreport their intakes more often than men and are more likely to do so if they think they are overweight or obese. The aim was to compare two methods to assess women’s diet and how well they associate with biomarkers. The influence and frequency of underreporting was also investigated. Methods: Diet of 53 women was assessed by two 24-hour recalls and a food frequency questionnaire (FFQ). Blood was analyzed for retinol, β-carotene, vitamin C and serum ferritin, and 24-hour urine for nitrogen, potassium and sodium. Underreporting was evaluated with nitrogen excretion vs. intake, and energy intake vs. basal metabolic rate. Results: Energy percent (E%) from macronutrients was similar from FFQ and 24-hour recalls, but total intake was higher from 24-hour recalls (9,516 ± 2,080 vs. 8,183 ± 2,893 kJ, p < 0.01). Intakes of vitamin C and potassium from both methods correlated with their respective biomarkers (r = 0.316–0.393). Underreporters had higher body mass index (BMI) than others (27.7 ± 5.5 vs. 23.8 ± 3.7 kg/m2, p < 0.05). They reported lower E% total fat (32 ± 5 vs. 38 ± 6 E%, p < 0.01) and higher E% carbohydrate (49 ± 4 vs. 45 ± 7 E%, p < 0.05). Correlation between intake and biomarkers increased after exclusion of underreporters. Conclusion: For women, FFQ and 24-hour recalls give similar E% and most nutrients correlate, but FFQ gives lower intake. Underreporters have higher BMI and diminish the correlation between calculated intake and biomarkers. This has to be considered when intake data are associated with weight management, disease and lifestyle factors.
Epidemiology and Initial Management of Ambiguous Genitalia at Birth in Germany
Authors: Thyen Ute , Lanz Kathrin , Holterhus Paul-Martin , Hiort Olaf
Published: August 2006

Background: In this epidemiological study, we sought to capture the incidence of ambiguous genitalia in neonates and to describe initial management strategies. Methods: We used the registry for rare diseases in pediatrics in Germany to ascertain cases and asked reporting institutions for information on phenotype, laboratory tests, imaging results, diagnosis, initial management and sex assignment. Results: We identified 80 cases within a 2-year study period and calculated an incidence of 2 per 10,000 births with ambiguous genitalia per year in Germany. Prevalence was higher in infants from non-German family background. In more than 50% of all infants a definite diagnosis was lacking even at the age of 6 months. In those cases where the etiology was confirmed, the most common diagnosis was congenital adrenal hyperplasia, followed by androgen insensitivity syndrome and mixed gonadal dysgenesis. Associated malformations were very common, affecting 37.5% of all infants. Sex assignment was female in 46,XY infants with predominately female phenotype and all 46,XX infants. Early surgery was performed in many cases irrespective whether a definite diagnosis had been established or not. Integrated psychosocial care was the exception rather than the rule. Conclusions: Classification and management of ambiguous genitalia at birth remain a challenge for all professionals involved. National and international registries may help to provide a better understanding of the incidence and clinical course of such disorders.
Incident Dementia Cases and Mortality
Authors: Gühne Uta , Matschinger Herbert , Angermeyer Matthias C. , Riedel-Heller Steffi G.
Published: August 2006

Mortality caused by dementia has mainly been examined in population-based studies relying on prevalent cases. This study aims to investigate the impact of incident dementia on mortality as well as to identify factors influencing the course of dementia and those predicting early death in demented individuals. A representative community sample of 1,692 individuals aged 75 years and over was examined by neuropsychological testing in a four-wave study. Data were analyzed with the Cox proportional hazards model after making necessary adjustments for potential covariates. At the third follow-up 51% of the incident demented and 19% of the participants without dementia had died. The mean survival time was 3.1 years (95% CI = 2.8–3.4) for the demented subjects and 4.0 years (95% CI = 3.9–4.0) for those without dementia (p < 0.001). In the total sample, the relative risk of dying after developing dementia was estimated to be 2.4 (95% CI = 1.6–3.6) with age, sex, education, co-morbidity, and institutionalization being taken into consideration. Those persons with incident dementia who died had a more severe dementia. Population-based studies relying on incident cases are especially valuable in describing course and outcome of dementia. Studies relying on prevalent cases and clinical samples tend to overestimate mortality and propose course-modifying factors that are challenged by studies relying on incident cases.
Refractory Heartburn to Proton Pump Inhibitors: Epidemiology, Etiology and Management
Authors: Sgouros Spiros N. , Mantides Apostolos
Published: August 2006

Patients with refractory heartburn to proton pump inhibitors (PPIs) represent a distinctive group which is difficult to manage. In a systematic review of the relative literature we found that approximately 20% of patients with erosive esophagitis and 15–25% of patients with normal endoscopy and abnormal 24-hour esophageal pH monitoring continue to report heartburn despite treatment with standard dose PPIs. Furthermore, approximately 30–40% of patients with normal endoscopy and 24-hour pH studies and 15–20% of patients with Barrett’s esophagus have refractory heartburn to double dose PPIs. In such cases, compliance to therapy, duodeno-gastroesophageal reflux, gastro-esophageal motility disorders and eradication of Helicobacter pylori infection may contribute to symptoms. Based on the available evidence, we suggested an algorithm for the evaluation and management of these patients.
Notes on the Vocabulary of Abyāne'ī
Authors: Joneidi-Ja'fari Mahmud
Published: August 2006

In his article, the author maintains the view that within the Central Iranian linguistic continuum, there is a separate dialect area including ten small villages, which he calls the Abyāne group, after the name of its most typical member. He supports his argument by discussing two characteristic isoglosses for this group—the terms for "mouth" and "dog".
Iranian Elements in Arabic the State of Research
Authors: Asatrian Mushegh
Published: August 2006

The article critically examines the extant literature on the problem of Iranian elements in Classical Arabic, classifying it into three categories: lexica, lexicological essays and notes, and general overviews. The last section of the paper discusses the phonetic peculiarities of the Iranian borrowings in Arabic.
Traditional Medicine in Bhutan
Authors: McKay Alex , Wangchuk Dorji
Published: August 2006

The Himalayan kingdom of Bhutan is an independent state situated between China and India. It emerged as a unified polity in the early 17th century under the rule of an exiled Tibetan religious leader and much of its elite culture, including its medical traditions, were brought from Tibet during this period. The Bhutanese Traditional Medical system subsequently evolved distinct characteristics that enable it to be viewed as a separate part of the Himalayan tradition of Sowa Rigpa (̒the science of healing̓), which includes what is now known as Tibetan Medicine. After coming under the influence of the British imperial Government of India at the beginning of the 20th century, Bhutan was occasionally visited by British Medical Officers from the Indian Medical Service, who accompanied British Political Officers on diplomatic missions there. But when the British withdrew from South Asia in 1947 there were no permanent biomedical structures or even fully qualified Bhutanese biomedical doctors in Bhutan. Since 194 7, Bhutan has evolved a state medical system in which their Traditional Medicine is an integral part and patients have the choice of treatment under traditional or biomedical practitioners. With particular reference to the role of The Institute of Traditional Medicine Services in Thimphu this paper discusses the history, structures and practices of traditional medicine in Bhutan, including its interaction with biomedicine.
On Measuring the Terms of the Turbulent Kinetic Energy Budget from an AUV
Authors: Goodman Louis , Levine Edward R. , Lueck Rolf G.
Published: August 2006

The terms of the steady-state, homogeneous turbulent kinetic energy budgets are obtained from measurements of turbulence and fine structure from the small autonomous underwater vehicle (AUV) Remote Environmental Measuring Units (REMUS). The transverse component of Reynolds stress and the vertical flux of heat are obtained from the correlation of vertical and transverse horizontal velocity, and the correlation of vertical velocity and temperature fluctuations, respectively. The data were obtained using a turbulence package, with two shear probes, a fast-response thermistor, and three accelerometers. To obtain the vector horizontal Reynolds stress, a generalized eddy viscosity formulation is invoked. This allows the downstream component of the Reynolds stress to be related to the transverse component by the direction of the finescale vector vertical shear. The Reynolds stress and the vector vertical shear then allow an estimate of the rate of production of turbulent kinetic energy (TKE). Heat flux is obtained by correlating the vertical velocity with temperature fluctuations obtained from the FP-07 thermistor. The buoyancy flux term is estimated from the vertical flux of heat with the assumption of a constant temperature–salinity (T–S) relationship. Turbulent dissipation is obtained directly from the usage of shear probes.

A multivariate correction procedure is developed to remove vehicle motion and vibration contamination from the estimates of the TKE terms. A technique is also developed to estimate the statistical uncertainty of using this estimation technique for the TKE budget terms. Within the statistical uncertainty of the estimates herein, the TKE budget on average closes for measurements taken in the weakly stratified waters at the entrance to Long Island Sound. In the strongly stratified waters of Narragansett Bay, the TKE budget closes when the buoyancy Reynolds number exceeds 20, an indicator and threshold for the initiation of turbulence in stratified conditions. A discussion is made regarding the role of the turbulent kinetic energy length scale relative to the length of the AUV in obtaining these estimates, and in the TKE budget closure.
Detecting Answer Copying Using the Kappa Statistic
Authors: Sotaridona Leonardo S. , van der Linden Wim J. , Meijer Rob R.
Published: August 2006

A statistical test for detecting answer copying on multiple-choice tests based on Cohen's kappa is proposed. The test is free of any assumptions on the response processes of the examinees suspected of copying and having served as the source, except for the usual assumption that these processes are probabilistic. Because the asymptotic null and alternative distributions of the kappa statistic are derived under the assumption of common marginal probabilities for all items, a recoding of the item alternatives is proposed to approximate this case. The results from a simulation study in this article show that under this recoding, the test approximates its nominal Type I error rates and has promising power functions.
The Effectiveness of Complementary Therapies on the Pain Experience of Hospitalized Children
Authors: Lassetter Jane H.
Published: August 2006

Pain is a complex phenomenon for children, and the concepts of hospitalization and pain are often linked in the minds of children. Despite best-practice guidelines and standards related to pain management, many hospitalized children continue to have unrelieved pain. This suggests that analgesics alone do not sufficiently relieve their discomfort. Complementary therapies may have an important role in holistic pediatric pain management. This review of literature evaluates available evidence related to the use and effectiveness of complementary therapies on the pain experience of children in hospital settings. Thirteen recent research articles relative to this topic were located and included in this review. A variety of complementary therapies, including relaxation, distraction, hypnosis, art therapies, and imagery, are included. Results of the research are mixed, and further investigation is required.
Physical activity and behaviour in dementia
Authors: Eggermont Laura H.P. , Scherder Erik J.A.
Published: August 2006

Physical activity can have a positive impact on cognition and well-being in older people. This article reviews and evaluates the effects of planned physical activity programmes on mood, sleep and functional ability in people with dementia. A total of 27 studies between 1974 and 2005 were found. Of these, four included participants living at home, two involved participants who were living either at home or in care homes and 21 included participants living solely in care homes. Since psychosocial intervention can reduce family caregiver burden, the break down of home-care and associated rates of institutionalization, the indirect effects of these physical activity programmes on the family caregiver are also explored. The scope for developing physical activity programmes for people with dementia in primary care using families and volunteers is discussed.
Use of Traditional Medicine and Globalized Complementary and Alternative Medicine Among Low-Income Cancer Service Users in Brazil
Authors: Tovey Philip , de Barros Nelson Filice , Hoehne Eduardo Luiz , Carvalheira José Barreto Campello
Published: August 2006

Background: Complementary and alternative medicine (CAM) has become increasingly high profile in prosperous countries over the past 2 decades. Alongside this has been a renewed interest in the use of traditional medicine (TM) in poorer countries. Academic attention has tended to focus on either CAM in rich countries or indigenous TM in poorer ones. However, such a differentiation leads to a potential to gloss over global complexities, such as the study of countries where both CAM and TM are a potentially significant part of health options. Brazil is just such a country. Brazil is marked by massive socioeconomic inequalities; cancer is its second highest cause of death. To date, there has been little research on CAM/TM in cancer care in Brazil. Purpose: The purpose of this study is to provide the first exploratory data on the proportion of the use of CAM and/or TM among low-income cancer service users in Brazil. Method: A survey of cancer patients was conducted in November 2004 in a public-sector hospital in a major city in Brazil. A random sample (n = 92) was generated from a list of all appointments scheduled during that month (n = 570). Eighty-nine of the 92 patients contacted (97%) completed the questionnaire. Results: Of the sample, 62.9% had used at least 1 form of CAM or TM. However, this headline figure is potentially misleading. The data reveal an almost total absence of use of non-indigenous international CAM; it also shows prayer to be a major contributor to the relatively high use rate. Discussion: On the basis of this small-scale exploratory study, there is no evidence that those international CAMs ubiquitous in the West are spreading to low-income cancer service users in Brazil (despite anecdotal evidence of its increasing presence in the country generally). Moreover, when excluding prayer, use of indigenous traditional medicine was found to be relatively low. Further research is needed to examine these findings on a larger scale and to explore the relative importance of social, cultural, and economic factors behind them.