bluuebunny/crossref_metadata_2025 huggingface dataset:
NEMESI, VIAGGIO NELLA MALATTIA DI UN MEDICO
Authors: Editors The
Published: May 2013

Book review of:Germano PilatiNEMESI, VIAGGIO NELLA MALATTIA DI UN MEDICORoma: Chronos – Nuove Voci, 2007Pagine: 124Prezzo: 13,00 euro
Adult growth hormone deficiency: academic extravagance or real clinical entity for the internist?
Authors: Scanelli Giovanni , Catapano Luca , Traverso Beatrice , Aimoni Claudia
Published: May 2013

The Growth Hormone (GH) continues to act lifelong: it has been described, in fact, an Adult Growth Hormone Deficiency (AGHD) syndrome, involving several organs and functions, whose clinical aspects greatly improve with the administration of human recombinant GH. The authors describe, evaluating the most recent data from the literature, the clinical picture, the pathophysiologic mechanisms, the diagnostic tools and the therapy of AGHD.
Complex and Multifaceted Therapy-Related Myeloid Neoplasm Following Laryngeal Cancer Treated with Cisplatin and Radiotherapy
Authors: Niscola Pasquale
Published: May 2013

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A Case of Recurrent Tumoral Calcinosis in a Young Female
Authors: Kumar Abhishek , Singh Pawan , Dobhal Heena
Published: May 2013

Tumoral calcinosis, a rare benign clinical condition resembling a neoplasm is characterized by calcium and phosphate deposits, usually located around large joints. It can be primary or secondary to renal failure and hyperparathyroidism. This report describes a rare case of tumoral calcinosis in a 13 years old girl presenting as a huge lump around left shoulder and elbow joint with discharging sinus over left infraclavicular region.

How to cite this article

Kumar A, Singh P, Dobhal H. A Case of Recurrent Tumoral Calcinosis in a Young Female. World J Endoc Surg 2013;5(1):18-20.
Comparison of the characteristics of ionospheric parameters obtained from FORMOSAT-3 and digisonde over Ascension Island
Authors: Chuo Y. J. , Lee C. C. , Chen W. S. , Reinisch B. W.
Published: May 2013

Abstract. Electron density profile data obtained from the FORMOSAT-3 radio occultation (RO) measurements over Ascension Island are used to study the bottomside thickness parameter B0 in the International Reference Ionosphere (IRI) model, scale height around the F region peak height, and other F2 region parameters. The RO data were collected when the radio occultation occurred at Ascension Island (345.6° E, 8.0° S) during the solar minimum activity period from May 2006 to April 2008. Results show that the B0 values are in moderate agreement with the ground-based observations in the equinox period (correlation coefficient r = 0.682) and winter (r = 0.570), with a strong correlation in summer (r = 0.750). The seasonal and diurnal variations in B0 over Ascension Island show peak values during the daytime and in winter. In addition, the B0 values were underestimated and overestimated in the RO measurements during the daytime and nighttime, respectively. Moreover, the comparison of scale heights shows that scale heights obtained from the retrieved data and digisonde observations are weakly correlation in all three seasons. Furthermore, although the effective scale height (HT) values were reverse of those obtained from the RO measurements and are higher during the nighttime than in the daytime, they are in good agreement with those from ground-based observations. This paper also provides a comprehensive discussion of the effect of the asymmetric ionospheric electron density profiles on RO measurements.
Dynamics of seawater carbonate chemistry, production, and calcification of a coral reef flat, Central Great Barrier Reef
Authors: Albright R. , Langdon C. , Anthony K. R. N.
Published: May 2013

Abstract. Ocean acidification is projected to shift coral reefs from a state of net accretion to one of net dissolution this century. Presently, our ability to predict global-scale changes to coral reef calcification is limited by insufficient data relating seawater carbonate chemistry parameters to in situ rates of reef calcification. Here, we investigate natural trends in carbonate chemistry of the Davies Reef flat in the central Great Barrier Reef on diel and seasonal timescales and relate these trends to benthic carbon fluxes by quantifying net ecosystem calcification (nec) and net community production (ncp). Results show that seawater carbonate chemistry of the Davies Reef flat is highly variable over both diel and seasonal timescales. pH (total scale) ranged from 7.92 to 8.17, pCO2 ranged from 272 to 542 μatm, and aragonite saturation state (Ωarag) ranged from 2.9 to 4.1. Diel cycles in carbonate chemistry were primarily driven by ncp, and warming explained 35% and 47% of the seasonal shifts in pCO2 and pH, respectively. Daytime ncp averaged 36 ± 19 mmol C m−2 h−1 in summer and 33 ± 13 mmol C m−2 h−1 in winter; nighttime ncp averaged −22 ± 20 and −7 ± 6 mmol C m−2 h−1 in summer and winter, respectively. Daytime nec averaged 11 ± 4 mmol CaCO3 m−2 h−1 in summer and 8 ± 3 mmol CaCO3 m−2 h−1 in winter, whereas nighttime nec averaged 2 ± 4 mmol and −1 ± 3 mmol CaCO3 m−2 h−1 in summer and winter, respectively. Net ecosystem calcification was positively correlated with Ωarag for both seasons. Linear correlations of nec and Ωarag indicate that the Davies Reef flat may transition from a state of net calcification to net dissolution at Ωarag values of 3.4 in summer and 3.2 in winter. Diel trends in Ωarag indicate that the reef flat is currently below this calcification threshold 29.6% of the time in summer and 14.1% of the time in winter.
NEAR REAL-TIME AUTOMATIC MARINE VESSEL DETECTION ON OPTICAL SATELLITE IMAGES
Authors: Máttyus G.
Published: May 2013

Abstract. Vessel monitoring and surveillance is important for maritime safety and security, environment protection and border control. Ship monitoring systems based on Synthetic-aperture Radar (SAR) satellite images are operational. On SAR images the ships made of metal with sharp edges appear as bright dots and edges, therefore they can be well distinguished from the water. Since the radar is independent from the sun light and can acquire images also by cloudy weather and rain, it provides a reliable service. Vessel detection from spaceborne optical images (VDSOI) can extend the SAR based systems by providing more frequent revisit times and overcoming some drawbacks of the SAR images (e.g. lower spatial resolution, difficult human interpretation). Optical satellite images (OSI) can have a higher spatial resolution thus enabling the detection of smaller vessels and enhancing the vessel type classification. The human interpretation of an optical image is also easier than as of SAR image. In this paper I present a rapid automatic vessel detection method which uses pattern recognition methods, originally developed in the computer vision field. In the first step I train a binary classifier from image samples of vessels and background. The classifier uses simple features which can be calculated very fast. For the detection the classifier is slided along the image in various directions and scales. The detector has a cascade structure which rejects most of the background in the early stages which leads to faster execution. The detections are grouped together to avoid multiple detections. Finally the position, size(i.e. length and width) and heading of the vessels is extracted from the contours of the vessel. The presented method is parallelized, thus it runs fast (in minutes for 16000 × 16000 pixels image) on a multicore computer, enabling near real-time applications, e.g. one hour from image acquisition to end user.
USING MORPHOLOGICAL DIFFERENTIAL ATTRIBUTE PROFILES FOR CHANGE CATEGORIZATION IN HIGH RESOLUTION SAR IMAGES
Authors: Boldt M. , Schulz K. , Thiele A. , Hinz S.
Published: May 2013

Abstract. Change detection in urban and suburban areas through remote sensing satellite imagery is an important topic. Furthermore, it is of special interest to derive information on the category of detected changes is of special interest. In Boldt et al. (2012), a fullyautomatic change detection method based on a morphological filtered ratio image was presented. This filter step is accomplished by an alternating sequential filter (ASF), which supports the knowledge-driven analysis of the scene. For example, the focus can be set on small-scaled changes caused by vehicles or smaller construction sites. The change detection itself is performed using the automatic threshold method shown in Sahoo et al. (2004) considering the entropies of the fore- and background of the filtered ratio image. In contrast, the presented approach makes use of morphological differential attribute profiles (DAPs) to compare changes detected in high resolution (HR) TerraSAR-X (TSX) amplitude images of Greding (Germany). DAPs are the derivatives of morphological attribute profiles (APs). APs are calculated by applying iteratively attribute openings and/or closings to an input image. Attribute openings (resp. closings) themselves are a combination of connected openings (closings) and trivial openings (closings). DAPs provide the opportunity to derive typical signatures for each pixel of the entire image (Dalla Mura et al., 2010), and, as a consequence, for each detected change segment. Aiming on the categorization of changes, it is shown in this paper that the DAPs represent a promising method for detecting changes with similar semantics automatically.
Environmental Influences on the Development of Endometriosis
Authors: Carmona Francisco , Martínez-Zamora Angeles , Bassols María L. , Balasch Juan
Published: May 2013

Purpose

Several environmental toxicants (ETs), including dioxins and dioxin-like compounds (DLCs), perfluorochemicals, organochlorine pesticides, phthalates, and heavy metals (especially cadmium with its estrogen-like properties in animal models) have been investigated as possibly being related to endometriosis.

Methods

Systematic review of pertinent literature.

Results

DLCs have been the most investigated ETs. DLCs are persistent organic pollutants with highly toxic potential and include three types of compounds: polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) or furans, and polychlorinated biphenyls (PCBs). The most toxic is 2, 3, 7, 8- tetrachlorodibenzo-p-dioxin (TCDD). The connection mechanism between dioxins and endometriosis is still unclear. However, dioxins and DLCs are endocrine-disrupting compounds that can affect the pathobiology of endometriosis at multiple levels. Part of the dioxin and DLCs toxic effects can be accounted for by their interaction with the aryl hydrocarbon receptor (AhR). It has been proposed that dioxin can initiate or promote endometriosis by means of interaction with estrogen receptors or by suppressing the expression of progesterone receptors. Furthermore, TCDD alters the expression of cytokines and growth factors, remodeling enzymes and cytochrome P450 expression and activity.

Conclusions

Studies in rhesus models have revealed a correlation between dioxin exposure and endometriosis. However, evidence from epidemiologic studies is inconclusive.
The Role of Psychographic Factors in Nature-Based Tourist Expenditure
Authors: Veisten Knut , Lindberg Kreg , Grue Berit , Haukeland Jan Vidar
Published: May 2013

Numerous studies have examined the relationship between tourist expenditure and observable characteristics of the individual and the trip. We add latent variables based on psychographic factors into a model of expenditure by nature-based tourists. This study models the log of per person trip expenditure by domestic and international visitors in a Norwegian alpine national park region as a function of psychographic factors as well as traditional measures of trip and demographic characteristics. In the regression models, factor scores were utilized from nature orientation, recreation experience preference (REP), a new ecological paradigm (NEP) and wilderness preference (WPS) scales. Higher scores on a NEP environmentalism factor were associated with higher expenditure, while higher scores on a REP risk seeking factor were associated with lower expenditure. Higher scores on a risk seeking, or challenge factor, from the nature orientation scale was associated with lower expenditure, while higher scores on an inspiration seeking factor were associated with higher expenditure. Structural equation models were then estimated for comparison. The implications for tourism management and marketing are discussed.
Reduction of Wingtip Vortex from Suction at Wingtip
Authors: Samal Sangram Keshari , Dash P. K.
Published: May 2013

The editorial board announced this article has been retracted on November 3, 2017.

If you have any further question, please contact us at: mer@ccsenet.org
Where Water and Energy Meet
Authors: Krupinskey Dru , Diffenderfer Robert P.
Published: May 2013

Within the context of our changing climate, it is becoming increasingly important to create a meaningful and transparent method for measuring and reporting the water‐energy connection to achieve a sustainable supply of both. It generally takes water to make energy, and because treating and moving water is such an energy‐intensive process, it has become apparent that water and energy are inextricably linked.
Key Issues for Congress
Authors: Holmes Tommy
Published: May 2013

The 113th session of the US Congress is well under way. For the water community, two issues will dominate the legislative arena in this session: water infrastructure finance and cybersecurity. Yes, fierce partisanship still causes legislative gridlock on many issues, but infrastructure investment and security are among the few areas where legislators can come together.
Using Technology to Balance Algebraic Explorations
Authors: Kurz Terri L.
Published: May 2013

Free, Web-based balance tools can help students visualize the concept of the equal sign as the pivot point of an equation.
Is It a Pattern?
Authors: McGarvey Lynn M.
Published: May 2013

A child's decision-making photo activity about pattern identification presents implications for teaching and learning patterns in the early years.
Effective and Rapid Osteoclast Inhibition by Denosumab, is Reflected in Serum C Telopeptide (CTX), Across Different Tumor Types
Authors: S. Tuyls  , F. Geurs  , Y. Deprest
Published: May 2013

Denosumab, a monoclonal antibody against RANKL has superior efficacy against bone metastases. Its in vivo activity can be measured recently by dosing of serum C telopeptide, produced by collagen destruction by the osteoclast. We report the first patient series, across several tumor types of the efficacy of denosumab in normalising serum CTX.
Surgery Versus Radiation Therapy in Symptomatic Malignant Spinal Cord Compression
Authors: Kenneth D. Bishop  , Meghana Rao  , Peter J. Quesenberry
Published: May 2013

Malignant epidural spinal cord compression is an oncologic emergency that often results in pain and neurologic dysfunction, which may be permanent. Few prospective studies have been performed to determine whether surgical intervention confers a significant benefit over radiation therapy. We believe the small amount of existing evidence to support surgical intervention or radiation therapy alone suffers from patient selection bias, and that such bias tends to bear out in practice as well. In addition to the objective benefits achieved by surgical decompression, practitioners need to consider the subjective benefits such as increased ambulatory ability, increased spine stability, and improved pain management provided by timely surgical decompression of metastatic spinal cord lesions.
Photoacoustic Imaging for Cancer Diagnosis
Authors: Toshihiro Kushibiki  , Miya Ishihara
Published: May 2013

Photoacoustic imaging (PAI) is a unique modality that overcomes the resolution and depth limitations of optical imaging of tissues while maintaining relatively high contrast. In this article, we reviewthe biomedical applications of PAI, assisted or unassisted by exogenous photoabsorbers (contrast agents). Representative endogenous contrast agents include melanin and hemoglobin, whereas exogenous contrast agents include dyes, metal nanoparticles, and other constructs that absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic responses. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications including detection of cancer cells, sentinel lymph nodes, micrometastases, and monitoring of angiogenesis. Multi-functional agents have also been developed that can carry medicines or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents are used to guide and monitor therapeutic procedures. Overall, photoacoustic imaging has significant potential to assist in diagnosis, therapeutic planning, and monitoring of treatment outcome for cancers and other pathologies.
Biological and Pathological Study of Prostate Cancer at Localized Stage in Western Algeria
Authors: Abdelkrim Berroukche  , Malika Bendahmane-Salmi  , Badreddine Abdelkrim Kandouci
Published: May 2013

Objective:Toshow the contribution of the pathological examination, associated with prostatic specific antigen (PSA), in the early detection of prostate cancer in Western Algeria.
Methodology:This study focused on 160 cases, old between 50-80 years, with histologically confirmed prostate adenocarcinoma and carried out in urology hospitals in western Algeria during the period from 2007 to 2011. Tumor stage, PSA, Gleason score and the degree of tumor differentiation were analyzed.
Results:135 patients, with a poor prognosis and a Gleason score > 8 index of incurable malignant aggression, have not been the subject of this study. But the other 35 patients were candidates because they had a favorable prognosis with a localized stage that could be curable. Gleason score was between 5-6 in 5 patients with TPSA  10 ng / ml at differential stage, score of 7 in 10 patients with TPSA between 10-20 ng / ml atmoderately differentiated stage and finally a score of 8 in 20 patients with TPSA between 20,1-50 ng / ml at apoorly differentiated stage.
Conclusion:There is a strong correlation between TPSA, Gleason score and the degree of tumor differentiation. Biological and pathological prognosis, established early, can reduce tumor progression.
Nitric Oxide Metabolites Change in Cisplatin-Induced Nephrotoxicity: The Effect of L-Arginine and Losartan
Authors: Zahra Pezeshki  , Mehdi Nematbakhsh
Published: May 2013

Cisplatin (CP) is an anticancer drug with the most common side effect of nephrotoxicity. CP also alters the level of nitric oxide (NO), and NO itself may promote CP-induced nephrotoxicity. In this short report, we measured the serum levels of NO metabolites in an animal model of CP-induced nephrotoxicity, and tested the effect of two nephroprotectant agents; l-arginine and losartan on serum levels of NO metabolites. The results indicated that CP increased the serum concentration of nitrite but not nitrate. However, l-arginine and losartan significantly decreased the serum level of nitrite. It seems that l-arginine and losartan provide their nephroprotectant effect against CP-induced nephrotoxicity by reducing the serum level of nitrite.
A Generalization of the «Lady-Tasting-Tea» Procedure to Link Qualitative and Quantitative Approaches in Psychiatric Research
Authors: Falissard Bruno , Milman Daniel , Cohen David
Published: May 2013

In Fisher’s “The Design of Experiments”, a trial was designed to test a lady’s claim to be able to discriminate whether the milk or the tea was added first to a cup. In this trial, eight cups are poured, four with milk first and four with tea first. They are then presented in random order to a subject who has to divide them into two sets of 4, according his/her belief about the "treatment" received. The present paper generalizes this design so that a hypothesis concerning the existence of two sub groups in a set of psychiatric patient records (whether written, audiotaped or videotaped) can be tested rigorously from a statistical point of view. Tables are proposed to enable power and sample size calculations. A real example is presented; it shows that psycho-dynamically oriented professionals are able to discriminate seven healthy adults who have experienced a sibling’s cancer during childhood or adolescence from seven matched controls. This method is particularly suited to small sample studies that explore elusive clinical hypotheses traditionally tackled with qualitative methodologies.
Accounting for the Hierarchical Structure in Veterans Health Administration Data: Differences in Healthcare Utilization between Men and Women Veterans
Authors: Allore Heather G. , Ning Yuming , Brandt Cynthia A. , Goulet Joseph L.
Published: May 2013

Women currently constitute 15% of active United States of America military service personnel, and this proportion is expected to double in the next 5 years. Previous research has shown that healthcare utilization and costs differ in women US Veterans Health Administration (VA) patients compared to men. However, none have accounted for the potential effects of clustering on their estimates of healthcare utilization. US Women Veterans are more likely to serve in specific military branches (e.g. Army), components (e.g. National Guard), and ranks (e.g. officer) than men. These factors may confer different risk and protection that can affect subsequent healthcare needs. Our study investigates the effects of accounting for the hierarchical structure of data on estimates of the association between gender and VA healthcare utilization. The sample consisted of data on 406,406 Veterans obtained from VA’s Operation Enduring Freedom/ Operation Iraqi Freedom roster provided by Defense Manpower Data Center — Contingency Tracking System Deployment File. We compared three statistical models, ordinary, fixed and random effects hierarchical logistic regression, in order to assess the association of gender with healthcare utilization, controlling for branch of service, component, rank, age, race, and marital status. Gender was associated with utilization in ordinary logistic and, but not in fixed effects hierarchical logistic or random effects hierarchical logistic regression models. This points out that incomplete inference could be drawn by ignoring the military structure that may influence combat exposure and subsequent healthcare needs. Researchers should consider modeling VA data using methods that account for the potential clustering effect of hierarchy.
Association of aggression with a novel microRNA binding site polymorphism in the wolframin gene
Authors: Kovacs‐Nagy Reka , Elek Zsuzsanna , Szekely Anna , Nanasi Tibor , Sasvari‐Szekely Maria , Ronai Zsolt
Published: May 2013

Rare mutations in the WFS1 gene lead to Wolfram syndrome, a severe multisystem disorder with progressive neurodegeneration and diabetes mellitus causing life‐threatening complications and premature death. Only a few association studies using small clinical samples tested the possible effects of common WFS1 gene variants on mood disorders and suicide, the non‐clinical spectrum has not been studied yet. Self‐report data on Aggression, Impulsiveness, Anxiety, and Depression were collected from a large (N = 801) non‐psychiatric sample. Single nucleotide polymorphisms (SNPs) were selected to provide an adequate coverage of the entire WFS1 gene, as well as to include putative microRNA binding site polymorphisms. Molecular analysis of the assumed microRNA binding site variant was performed by an in vitro reporter‐gene assay of the cloned 3′ untranslated region with coexpression of miR‐668. Among the 17 WFS1 SNPs, only the rs1046322, a putative microRNA (miR‐668) binding site polymorphism showed significant association with psychological dimensions after correction for multiple testing: those with the homozygous form of the minor allele reported higher aggression on the Buss–Perry Aggression Questionnaire (P = 0.0005). Functional effect of the same SNP was also demonstrated in a luciferase reporter system: the minor A allele showed lower repression compared to the major G allele, if co‐expressed with miR‐668. To our knowledge, this is the first report describing a microRNA binding site polymorphism of the WFS1 gene and its association with human aggression based on a large, non‐clinical sample. © 2013 Wiley Periodicals, Inc.
Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial (Br J Surg 2013; 100: 970–975)
Authors: Rutten H
Published: May 2013

Worst with short course radiotherapy
Lymphangiogenesis in abdominal aortic aneurysm
Authors: Scott D J A , Allen C J , Honstvet C A , Hanby A M , Hammond C , Johnson A B , Perry S L , Jones P F
Published: May 2013

Background

Ongoing angiogenesis is implicated in the inflammatory environment that characterizes abdominal aortic aneurysm (AAA). Although lymphangiogenesis has been associated with chronic inflammatory conditions, it has yet to be demonstrated in AAA. The aim was to determine the presence of lymphangiogenesis and to delineate the relationship between inflammation and neovascularization in AAA tissue.

Methods

AAA samples and preoperative computed tomography images were obtained from patients undergoing elective AAA repair. Control samples were age-matched abdominal aortic tissue. Specific immunostains for blood vessels (CD31, CD105), lymphatic vessels (D2-40), vascular endothelial growth factor (VEGF) A and VEGF receptor (VEGFR) 3 allowed characterization and quantitation of vasculature.

Results

The AAA wall contained high levels of inflammatory infiltrate; microvascular densities of blood (P < 0·001) and lymphatic (P = 0·003) vessels were significantly increased in AAA samples compared with controls. Maximal AAA vascularity was observed in inflammatory areas, with vessels that stained positively for CD31 (ρ = 0·625, P = 0·017), CD105 (ρ = 0·692, P = 0·009) and D2-40 (ρ = 0·675, P = 0·008) correlating positively with the extent of inflammation. Increased VEGFR-3 and VEGF-A expression was also evident within inflammatory AAA areas.

Conclusion

These findings demonstrated lymphatic vessel involvement in end-stage AAA disease, which was associated with the degree of inflammation, and confirmed the involvement of neovascularization.
Forecasting deforestation and carbon emissions in tropical developing countries facing demographic expansion: a case study in Madagascar
Authors: Vieilledent Ghislain , Grinand Clovis , Vaudry Romuald
Published: May 2013

Anthropogenic deforestation in tropical countries is responsible for a significant part of global carbon dioxide emissions in the atmosphere. To plan efficient climate change mitigation programs (such as REDD+, Reducing Emissions from Deforestation and forest Degradation), reliable forecasts of deforestation and carbon dioxide emissions are necessary. Although population density has been recognized as a key factor in tropical deforestation, current methods of prediction do not allow the population explosion that is occurring in many tropical developing countries to be taken into account. Here, we propose an innovative approach using novel computational and statistical tools, including R/GRASS scripts and the new phcfM R package, to model the intensity and location of deforestation including the effect of population density. We used the model to forecast anthropogenic deforestation and carbon dioxide emissions in five large study areas in the humid and spiny‐dry forests of Madagascar. Using our approach, we were able to demonstrate that the current rapid population growth in Madagascar (+3.39% per year) will significantly increase the intensity of deforestation by 2030 (up to +1.17% per year in densely populated areas). We estimated the carbon dioxide emissions associated with the loss of aboveground biomass to be of 2.24 and 0.26 tons per hectare and per year in the humid and spiny‐dry forest, respectively. Our models showed better predictive ability than previous deforestation models (the figure of merit ranged from 10 to 23). We recommend this approach to reduce the uncertainty associated with deforestation forecasts. We also underline the risk of an increase in the speed of deforestation in the short term in tropical developing countries undergoing rapid population expansion.
High resolution 13CNMR detection of short‐ and medium‐chain synthetic triacylglycerols used in butterfat adulteration
Authors: Picariello Gianluca , Sacchi Raffaele , Fierro Olga , Melck Dominique , Romano Raffaele , Paduano Antonello , Motta Andrea , Addeo Francesco
Published: May 2013

Recently in European countries, control laboratories have revealed real cases of deceptive practices in which synthetic triacylglycerols (TAGs) were used for adulterating butterfat. The complex fat blends are difficult to detect with the classical methods of analysis, especially when the adulterating TAGs contain fatty acids (FAs) in the proportions similar to that of genuine butter. Nevertheless, because butyric acid (C4) exclusively occurs at the sn‐3 position in milk fat TAGs, the determination of its distribution on the glycerol backbone provides a diagnostic indicator to differentiate genuine butter from mixtures with synthetic TAGs. Herein, we have demonstrated the straightforward application of mono‐dimensional 13C NMR spectroscopy for detecting synthetic TAGs in mixtures with authentic butterfat. The method is based on the 13C NMR determination of the regioisomeric distribution of C4 between the sn‐1,3‐ and sn‐2‐positions and boasts several analytical advantages, such as specificity, robustness and minimal sample handling. The limit of detection (LOD) and limit of quantification (LOQ) of the synthetic fats, estimated to be 1 and 2.5% w/w, respectively, easily surpass the limit of 10% at which a fraudulent practice might be economically attractive.

Practical applications We have developed a robust and efficient method, based on high resolution 13C NMR spectroscopy, for detecting the adulteration of butterfat with synthetic low‐ and medium‐carbon number TAG mixtures. In milk fat TAGs, butyric acid is esterified exclusively at the sn‐3 position of the glycerol backbone. Thus, the method relies on 13C NMR monitoring of the carbonyl resonance of butyric acid at the sn‐2 glycerol position, which is diagnostic of synthetic or interesterified TAGs. The 13C NMR‐based analysis overcomes the pitfalls of traditional pattern recognition methodologies for the assessment of butter authenticity, which can be ineffective when butter is adulterated with synthetic TAGs obtained from FA in proportions similar to those of natural milk fat. The method achieves reliable quantification up to 2.5% w/w of adulterating fats (LOQ) and can detect quantities as low as 1% w/w of synthetic TAGs blended with butter (LOD).
Molecular diagnosis of endometrial cancer from uterine aspirates
Authors: Perez‐Sanchez Cristina , Colas Eva , Cabrera Silvia , Falcon Orlando , Sanchez‐del‐Río Angel , García Enrique , Fernández‐de‐Castillo Luis , Muruzabal Juan Carlos , Alvarez Elena , Fiol Gabriel , González Carmen , Torrejón Rafael , Moral Eloy , Campos Miriam , Repollés Manuel , Carreras Ramon , Jiménez‐López Jesus , Xercavins Jordi , Aibar Elena , Perdones‐Montero Alvaro , Lalanne Eric , Palicio Marta , Maes Tamara , Rosell‐Vives Elisabet , Nieto Carlos , Ortega Alicia , Pedrola Nuria , Llauradó Marta , Rigau Marina , Doll Andreas , Abal Miguel , Ponce Jordi , Gil‐Moreno Antonio , Reventós Jaume
Published: May 2013

Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using quantitative reverse transcriptase‐polymerase chain reaction on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of five genes and evaluated their ability to diagnose EC. The algorithms were tested in a prospective, double‐blind, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case–control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76 to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies and helps to identify additional cases.
Hybrid in silico models for drug‐induced liver injury using chemical descriptors and in vitro cell‐imaging information
Authors: Zhu Xiang‐Wei , Sedykh Alexander , Liu Shu‐Shen
Published: May 2013

Drug‐induced liver injury (DILI) is a major adverse drug reaction that accounts for one‐third of post‐marketing drug withdrawals. Several classifiers for human hepatotoxicity using chemical descriptors with limited prediction accuracies have been published. In this study, we developed predictive in silico models based on a set of 156 DILI positive and 136 DILI negative compounds for DILI prediction. First, models based on a chemical descriptor (CDK, Dragon and MOE) and in vitro cell‐imaging endpoints [human hepatocyte imaging assay technology (HIAT) descriptors] were built using random forest (RF) and five‐fold cross‐validation procedure. Then three hybrid models were built using HIAT and a single type of chemical descriptors. Generally, the models based only on chemical descriptors were poor, with a correct classification rate (CCR) around 0.60 when the default threshold value (i.e. threshold = 0.50) was used. The hybrid models afforded a CCR of 0.73 with a specificity of 0.74 and a better true positive rate (sensitivity of 0.71), which is crucial in drug toxicity screening for the purpose of patient safety. The benefit of hybrid models was even more drastic when stricter classification thresholds were employed (e.g. CCR would be 0.83 when double thresholds (non‐toxic < 0.40 and toxic > 0.60) were used for the hybrid model). We have developed rigorously validated hybrid models which can be used in virtual screening of lead compounds with potential hepatotoxicity. Our study also showed a chemical structure and in vitro biological data can be complementary in enhancing the prediction accuracy of human hepatotoxicity and can afford rational mechanistic interpretation. Copyright © 2013 John Wiley & Sons, Ltd.
Delivery of S1P receptor‐targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect
Authors: Das Anusuya , Tanner Shaun , Barker Daniel A. , Green David , Botchwey Edward A.
Published: May 2013

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic‐co‐glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1‐phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow‐degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro‐computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in‐growth and an increase in new bone formation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1210‐1218, 2014.
ATF4 promotes bone angiogenesis by increasing vegf expression and release in the bone environment
Authors: Zhu Ke , Jiao Hongli , Li Shuai , Cao Huiling , Galson Deborah L , Zhao Zhongfang , Zhao Xi , Lai Yumei , Fan Jie , Im Hee-Jeong , Chen Di , Xiao Guozhi
Published: May 2013

Activating transcription factor 4 (ATF4) is a critical transcription factor for bone remodeling; however, its role in bone angiogenesis has not been established. Here we show that ablation of the Atf4 gene expression in mice severely impaired skeletal vasculature and reduced microvascular density of the bone associated with dramatically decreased expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in osteoblasts located on bone surfaces. Results from in vivo studies revealed that hypoxia/reoxygenation induction of HIF-1α and VEGF expression leading to bone angiogenesis, a key adaptive response to hypoxic conditions, was severely compromised in mice lacking the Atf4 gene. Loss of ATF4 completely prevented endothelial sprouting from embryonic metatarsals, which was restored by addition of recombinant human VEGF protein. In vitro studies revealed that ATF4 promotion of HIF-1α and VEGF expression in osteoblasts was highly dependent upon the presence of hypoxia. ATF4 interacted with HIF-1α in hypoxic osteoblasts, and loss of ATF4 increased HIF-1α ubiquitination and reduced its protein stability without affecting HIF-1α mRNA stability and protein translation. Loss of ATF4 increased the binding of HIF-1α to prolyl hydroxylases, the enzymes that hydroxylate HIF-1a protein and promote its proteasomal degradation via the pVHL pathway. Furthermore, parathyroid hormone-related protein (PTHrP) and receptor activator of NF-κB ligand (RANKL), both well-known activators of osteoclasts, increased release of VEGF from the bone matrix and promoted angiogenesis through the protein kinase C- and ATF4-dependent activation of osteoclast differentiation and bone resorption. Thus, ATF4 is a new key regulator of the HIF/VEGF axis in osteoblasts in response to hypoxia and of VEGF release from bone matrix, two critical steps for bone angiogenesis.
In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model
Authors: Lynch Maureen E , Brooks Daniel , Mohanan Sunish , Lee Min Joon , Polamraju Praveen , Dent Kelsey , Bonassar Lawrence J , van der Meulen Marjolein C H , Fischbach Claudia
Published: May 2013

Bone metastasis, the leading cause of breast cancer-related deaths, is characterized by bone degradation due to increased osteoclastic activity. In contrast, mechanical stimulation in healthy individuals upregulates osteoblastic activity, leading to new bone formation. However, the effect of mechanical loading on the development and progression of metastatic breast cancer in bone remains unclear. Here, we developed a new in vivo model to investigate the role of skeletal mechanical stimuli on the development and osteolytic capability of secondary breast tumors. Specifically, we applied compressive loading to the tibia following intratibial injection of metastatic breast cancer cells (MDA-MB231) into the proximal compartment of female immunocompromised (SCID) mice. In the absence of loading, tibiae developed histologically-detectable tumors with associated osteolysis and excessive degradation of the proximal bone tissue. In contrast, mechanical loading dramatically reduced osteolysis and tumor formation and increased tibial cancellous mass due to trabecular thickening. These loading effects were similar to the baseline response we observed in non-injected SCID mice. In vitro mechanical loading of MDA-MB231 in a pathologically relevant 3D culture model suggested that the observed effects were not due to loading-induced tumor cell death, but rather mediated via decreased expression of genes interfering with bone homeostasis. Collectively, our results suggest that mechanical loading inhibits the growth and osteolytic capability of secondary breast tumors after their homing to the bone, which may inform future treatment of breast cancer patients with advanced disease. © 2013 American Society for Bone and Mineral Research
Residence time distribution determination in a submerged filter with and without aeration using a tracer
Authors: Cobos‐Becerra Yazmín Lucero , González‐Martínez Simón
Published: May 2013

BACKGROUND

Commercial filter media are commonly regular in shape and the flow patterns can be predicted with simple tools. Using lava stones as filter media, this study analyzes the influence of particle size and aeration on the hydraulic behaviour of a submerged filter prior to biofilm colonization.

RESULTS

The filter was packed, separately, with two different sizes of lava stones (4.7 and 9.5 mm) and operated under different hydraulic retention times to establish the causes of deviations from ideal models. Tracer curves were analyzed using two mathematical models (Axial Dispersion and Wolf and Resnick models). The curves show that the tracer appeared in the effluent in a shorter time than expected indicating an effective volume reduction. It was estimated that the dead volume of the filter with aeration was 83% and 22% for the filter without aeration.

CONCLUSION

The dead volume is caused, in the case of the filter with aeration, by the combination of two phenomena: the liquid volume displaced by the air bubbles and the turbulence caused by aeration generating preferential channelling along the filter media and creating large zones of stagnant liquid. In the case of the filter without aeration the volume reduction is caused by channels developed by the media irregular shape. © 2013 Society of Chemical Industry
Synthesis of a phenolic precursor and its efficient O‐[18F]fluoroethylation with purified no‐carrier‐added [18F]2‐fluoroethyl brosylate as the labeling agent
Authors: Jarkas Nashwa , Voll Ronald J. , Goodman Mark M.
Published: May 2013

[18F]2‐Fluoroethyl‐p‐toluenesulfonate also called [18F]2‐fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [18F]2‐Fluoroethyl‐4‐bromobenzenesulfonate, also called [18F]2‐fluoroethyl brosylate ([18F]F(CH2)2OBs), was used as an alternative radiolabeling agent to prepare [18F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O‐fluoroethylating the phenolic precursor. Purified by reverse‐phase HPLC, the no‐carrier‐added [18F]F(CH2)2OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [18F]F(CH2)2OBs with the phenolic precursor was performed by heating in DMF and successfully produced [18F]FEOHOMADAM, after HPLC purification, in RCY of 21%. Copyright © 2013 John Wiley & Sons, Ltd.
Lack of effect of bioactive‐rich extracts of pomegranate, persimmon, nettle, dill, kale andSideritisand isolated bioactives on platelet function
Authors: Hollands Wendy J , Saha Shikha , Hayran Osman , Boyko Nadiya , Glibetic Maria , Konic‐Ristic Aleksandra , Jorjadze Mariam , Kroon Paul A
Published: May 2013

BACKGROUND

The health benefits of fruit and vegetable‐rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive‐rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n=15 subjects) were treated with extracts of bioactive‐rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using thePFA‐100.

RESULTS

None of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes inPFA‐100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases inCTfor the platelet agonists epinephrine andADP, respectively.

CONCLUSION

These data do not support the notion that these plant bioactives can improve human platelet function. © 2013 Society of Chemical Industry
Nutraceutical nanoemulsions: influence of carrier oil composition (digestible versus indigestible oil) on β‐carotene bioavailability
Authors: Rao Jiajia , Decker Eric Andrew , Xiao Hang , McClements David Julian
Published: May 2013

BACKGROUND

Carotenoids, such as β‐carotene, are widely used in foods and beverages as natural colorants and nutraceuticals. We investigated the influence of carrier oil composition (ratio of digestible to indigestible oil) on the physical stability, microstructure and bioaccessibility of β‐carotene nanoemulsions using a simulated gastrointestinal tract model.

RESULTS

β‐Carotene nanoemulsions (d < 150 nm) were formed by high‐pressure homogenization using sucrose monoester and lysolecithin as emulsifiers, and mixtures of corn oil (digestible) and lemon oil (indigestible) as the lipid phase. All of the nanoemulsions underwent extensive droplet aggregation under mouth, stomach and small intestine conditions. The extent of free fatty acid production in the small intestine increased as the amount of digestible oil in the droplets increased. The bioaccessibility of β‐carotene also increased with increasing digestible oil content, ranging from ∼5% for the pure lemon oil system to ∼76% for the pure corn oil system. This effect was attributed to the ability of mixed micelles formed from triglyceride digestion products (free fatty acids and monoglycerides) to solubilize β‐carotene.

CONCLUSIONS

This study provides important information for developing effective delivery systems for lipophilic bioactive components in food and beverage applications. © 2013 Society of Chemical Industry
Simultaneous screening of four epidermal growth factor receptor antagonists from Curcuma longa via cell membrane chromatography online coupled with HPLC–MS
Authors: Sun Meng , Ma Wei‐na , Guo Ying , Hu Zhi‐gang , He Lang‐chong
Published: May 2013

The epidermal growth factor receptors (EGFRs) are significant targets for screening active compounds. In this work, an analytical method was established for rapid screening, separation, and identification of EGFRs antagonists from Curcuma longa. Human embryonic kidney 293 cells with a steadily high expression of EGFRs were used to prepare the cell membrane stationary phase in a cell membrane chromatography model for screening active compounds. Separation and identification of the retention chromatographic peaks was achieved by HPLC–MS. The active sites, docking extents and inhibitory effects of the active compounds were also demonstrated. The screening result found that ar‐turmerone, curcumin, demethoxycurcumin, and bisdemethoxycurcumin from Curcuma longa could be active components in a similar manner to gefitinib. Biological trials showed that all of four compounds can inhibit EGFRs protein secretion and cell growth in a dose‐dependent manner, and downregulate the phosphorylation of EGFRs. This analytical method demonstrated fast and effective characteristics for screening, separation and identification of the active compounds from a complex system and should be useful for drug discovery with natural medicinal herbs.