bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the Canada Acute Coronary Syndrome Risk Score for Hospital Mortality in the Gulf Registry of Acute Coronary Events‐2
Authors: AlFaleh Hussam F. , Alsheikh‐Ali Alawi A. , Ullah Anhar , AlHabib Khalid F. , Hersi Ahmad , Suwaidi Jassim Al , Sulaiman Kadhim , Saif Shukri Al , Almahmeed Wael , Asaad Nidal , Amin Haitham , Al‐Motarreb Ahmed , Kashour Tarek
Published: September 2015

Background

Several risk scores have been developed for acute coronary syndrome (ACS) patients, but their use is limited by their complexity. The new Canada Acute Coronary Syndrome (C‐ACS) risk score is a simple risk‐assessment tool for ACS patients. This study assessed the performance of the C‐ACS risk score in predicting hospital mortality in a contemporary Middle Eastern ACS cohort.

Hypothesis

The C‐ACS score accurately predicts hospital mortality in ACS patients.

Methods

The baseline risk of 7929 patients from 6 Arab countries who were enrolled in the Gulf RACE‐2 registry was assessed using the C‐ACS risk score. The score ranged from 0 to 4, with 1 point assigned for the presence of each of the following variables: age ≥75 years, Killip class >1, systolic blood pressure <100 mm Hg, and heart rate >100 bpm. The discriminative ability and calibration of the score were assessed using C statistics and goodness‐of‐fit tests, respectively.

Results

The C‐ACS score demonstrated good predictive values for hospital mortality in all ACS patients with a C statistic of 0.77 (95% confidence interval [CI]: 0.74‐0.80) and in ST‐segment elevation myocardial infarction and non–ST‐segment elevation acute coronary syndrome patients (C statistic: 0.76, 95% CI: 0.73‐0.79; and C statistic: 0.80, 95% CI: 0.75‐0.84, respectively). The discriminative ability of the score was moderate regardless of age category, nationality, and diabetic status. Overall, calibration was optimal in all subgroups.

Conclusions

The new C‐ACS score performed well in predicting hospital mortality in a contemporary ACS population outside North America.
The gut microbiome in NAFLD and ALD
Authors: Kirpich Irina A. , Parajuli Dipendra , McClain Craig J.
Published: September 2015

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Noncirrhotic portal hypertension: An overview
Authors: Etzion Ohad , Koh Christopher , Heller Theo
Published: September 2015

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CT segmentation of dental shapes by anatomy‐driven reformation imaging and B‐spline modelling
Authors: Barone S. , Paoli A. , Razionale A. V.
Published: September 2015

Dedicated imaging methods are among the most important tools of modern computer‐aided medical applications. In the last few years, cone beam computed tomography (CBCT) has gained popularity in digital dentistry for 3D imaging of jawbones and teeth. However, the anatomy of a maxillofacial region complicates the assessment of tooth geometry and anatomical location when using standard orthogonal views of the CT data set. In particular, a tooth is defined by a sub‐region, which cannot be easily separated from surrounding tissues by only considering pixel grey‐intensity values. For this reason, an image enhancement is usually necessary in order to properly segment tooth geometries.

In this paper, an anatomy‐driven methodology to reconstruct individual 3D tooth anatomies by processing CBCT data is presented. The main concept is to generate a small set of multi‐planar reformation images along significant views for each target tooth, driven by the individual anatomical geometry of a specific patient. The reformation images greatly enhance the clearness of the target tooth contours. A set of meaningful 2D tooth contours is extracted and used to automatically model the overall 3D tooth shape through a B‐spline representation.

The effectiveness of the methodology has been verified by comparing some anatomy‐driven reconstructions of anterior and premolar teeth with those obtained by using standard tooth segmentation tools. Copyright © 2015 John Wiley & Sons, Ltd.
Free Energy Calculations using a Swarm‐Enhanced Sampling Molecular Dynamics Approach
Authors: Burusco Kepa K. , Bruce Neil J. , Alibay Irfan , Bryce Richard A.
Published: September 2015

Free energy simulations are an established computational tool in modelling chemical change in the condensed phase. However, sampling of kinetically distinct substates remains a challenge to these approaches. As a route to addressing this, we link the methods of thermodynamic integration (TI) and swarm‐enhanced sampling molecular dynamics (sesMD), where simulation replicas interact cooperatively to aid transitions over energy barriers. We illustrate the approach by using alchemical alkane transformations in solution, comparing them with the multiple independent trajectory TI (IT‐TI) method. Free energy changes for transitions computed by using IT‐TI grew increasingly inaccurate as the intramolecular barrier was heightened. By contrast, swarm‐enhanced sampling TI (sesTI) calculations showed clear improvements in sampling efficiency, leading to more accurate computed free energy differences, even in the case of the highest barrier height. The sesTI approach, therefore, has potential in addressing chemical change in systems where conformations exist in slow exchange.
Providing Access to Genomic Variant Knowledge in a Healthcare Setting: A Vision for the ClinGen Electronic Health Records Workgroup
Authors: Overby CL , Heale B , Aronson S , Cherry JM , Dwight S , Milosavljevic A , Nelson T , Niehaus A , Weaver MA , Ramos EM , Williams MS
Published: September 2015

The Clinical Genome Resource (ClinGen) is a National Institutes of Health (NIH)‐funded collaborative program that brings together a variety of projects designed to provide high‐quality, curated information on clinically relevant genes and variants. ClinGen's EHR (Electronic Health Record) Workgroup aims to ensure that ClinGen is accessible to providers and patients through EHR and related systems. This article describes the current scope of these efforts and progress to date. The ClinGen public portal can be accessed at www.clinicalgenome.org.
Nonplanar Shocks and Solitons in a Strongly Coupled Adiabatic Plasma: the Roles of Heavy Ion Dynamics and Nonextensitivity
Authors: Ema S. A. , Hossen M. R. , Mamun A. A.
Published: September 2015

An investigation has been made on heavy ion‐acoustic (HIA) nonplanar shocks and solitons in an unmagnetized, collisionless, strongly coupled plasma whose constituents are strongly correlated adiabatic inertial heavy ions, weakly correlated nonextensive distributed electrons and Maxwellian light ions. By using appropriate nonlinear equations for our strongly coupled plasma system and the well‐known reductive perturbation technique, a modified Burgers (mB) equation and a modified Korteweg‐de Vries (mK‐dV) equation have been derived. They are also numerically solved in order to investigate the basic features (viz. polarity, amplitude, width, etc.) of cylindrical and spherical shock/solitary waves in such a strongly coupled plasma system. The roles of heavy ion dynamics, nonextensivity of electrons, and other plasma parameters arised in this investigation have significantly modified the basic features of the cylindrical and spherical HIA solitary and shock waves. The findings of our results obtained from this theoretical investigation may be useful in understanding the nonlinear phenomena associated with the cylindrical and spherical HIA waves both in space and laboratory plasmas. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
MicroRNAs as regulators of beta‐cell function and dysfunction
Authors: Osmai Mirwais , Osmai Yama , Bang‐Berthelsen Claus H. , Pallesen Emil M. H. , Vestergaard Anna L. , Novotny Guy W. , Pociot Flemming , Mandrup‐Poulsen Thomas
Published: September 2015

In the last decade, there has been an explosion in both the number of and knowledge about miRNAs associated with both type 1 and type 2 diabetes. Even though we are presently in the initial stages of understanding how this novel class of posttranscriptional regulators are involved in diabetes, recent studies have demonstrated that miRNAs are important regulators of the islet transcriptome, controlling apoptosis, differentiation and proliferation, as well as regulating unique islet and beta‐cell functions and pathways such as insulin expression, processing and secretion. Furthermore, a large number of miRNAs have been linked to diabetogenic processes induced by elevated levels of glucose, free fatty acids and inflammatory cytokines. Thus, miRNAs are novel therapeutic targets with the potential of protecting the beta‐cell, and there is proof of principle that miRNA antagonists, so‐called antagomirs, are effective in vivo for other disorders. miRNAs are exported out of cells in exosomes, raising the intriguing possibility of cell‐to‐cell communication between distant tissues via miRNAs and that miRNAs can be used as biomarkers of beta‐cell function, mass and survival. The purpose of this review is to provide a status on how miRNAs control beta‐cell function and viability in health and disease. Copyright © 2015 John Wiley & Sons, Ltd.
Cyclic dinucleotides modulate human T‐cell response through monocyte cell death
Authors: Tosolini Marie , Pont Frédéric , Verhoeyen Els , Fournié Jean‐Jacques
Published: September 2015

Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c‐di‐AMP and cGAMP, two adenosine‐based cyclic dinucleotides, activated T lymphocytes in an unusual manner through monocyte cell death. c‐di‐AMP and cGAMP induced the selective apoptosis of human monocytes, and T lymphocytes were activated by the direct contact with these dying monocytes. The ensuing T‐cell response comprised cell‐cycle exit, phenotypic maturation into effector memory cells and proliferation arrest, but not cell death. This quiescence was transient since T cells remained fully responsive to further restimulation. Together, our results depict a novel activation pattern for human T lymphocytes: a transient quiescence induced by c‐di‐AMP‐ or cGAMP‐primed apoptotic monocytes.
SNAr versus Buchwald–Hartwig Amination/Amidation in the Imidazo[2,1‐b][1,3,4]thiadiazole Series
Authors: Copin Chloé , Massip Stéphane , Léger Jean‐Michel , Jarry Christian , Buron Frédéric , Routier Sylvain
Published: September 2015

An original and efficient palladium‐catalyzed amination of imidazo[2,1‐b][1,3,4]thiadiazole is reported. The SNAr and Buchwald–Hartwig cross‐coupling reactions were investigated to access C‐2 aminated imidazo[1,2‐b][1,3,4]thiadiazole derivatives. The reaction conditions were optimized under microwave irradiation, and a wide range of amines were used to determine the scope and limitations of the method. To complete this study, the palladium‐catalyzed and SNAr amination reactions were compared to determine the best strategy. The X‐ray crystallographic data of imidazo[2,1‐b][1,3,4]thiadiazole derivative 20 was used to formally establish the structures of the products.
The pathogenesis of Prurigo nodularis – ‘Super‐Itch’ in exploration
Authors: Zeidler C. , Ständer S.
Published: September 2015

Prurigo nodularis (PN) is characterized by multiple hyperkeratotic nodules, papules and the presence of intensive pruritus. This leads to an impaired quality of life and high burden due not only to the severe itch but also the chronic, skin lesions and lack of treatment options.

The pathogenesis of PN is not completely clarified. Previous studies have demonstrated just how important the interaction between cutaneous nerve fibres and immune cells is. Besides a reduced intraepidermal nerve fibre density, there are increased dermal levels of neuropeptides such as substance P, calcitonin gene‐related peptide and nerve growth factor, as well as a predominant presence of eosinophils and mast cells. An interaction of these factors results in a complex relationship which will be discussed in this article.
Pruritus in psoriasis: An update
Authors: Szepietowski J.C. , Reich A.
Published: September 2015

Background and objective

Psoriasis is one of the most common chronic inflammatory skin diseases, found in about 1–3% of the general population. Pruritus affects about 60–90% of patients with psoriasis. The aim of this review was to summarize current knowledge about the pathogenesis and treatment of this symptom in psoriasis patients.

Results

Majority of psoriatic patients consider pruritus as the most bothersome symptom. The pathogenesis of pruritus is still unknown but the major concept of its origin is focused on neurogenic inflammation. Possible itch mediators include neuropeptides released from dermal nerve endings upon various stimuli, which were found to be abnormally expressed in itchy psoriatic plaques. Another important phenomenon supporting the idea of neurogenic inflammation as a key player in pruritus accompanying psoriasis is abnormal innervations of psoriatic skin. Possibly increased innervation density in psoriasis may decrease the threshold for pruritic stimuli. It is also suggested that pruritus in psoriasis might be related to abnormal functioning of the peripheral opioid system. Despite the high frequency of pruritus in psoriasis, to date there is no single antipruritic therapy dedicated specifically to treat itch in this disease.

Conclusions

Neurogenic inflammation seems to be important for itchiness in psoriasis. Treatment of pruritus in patients with psoriasis should be directed towards the resolution of skin lesions, as disease remission usually is linked with pruritus relief.
Electrochemical Performance of Carbon Onions Fabricated by Electric Arc‐Discharge Method
Authors: Ruan Chao , Leng Jinsong , Lian Yongfu
Published: September 2015

Arc discharged carbon onions (CNOs) were purified through successive ignition, acid wash, surfactant‐assisted dispersion, filtration and centrifugation. Cyclic voltammetry of the multistage separated products with a ferro/ferricyanide redox probe was employed to measure the heterogeneous electron transfer (HET) rate. It was found that metal (nickel) encapsulating CNOs yielded in an HET rate about 60 times higher than that of hollow CNOs. The electrochemical performances of CNOs are interfered by the residual metal catalyst and nano‐graphitic debris, and are dependent on their varying morphology and structure. This work implicates that the metal encapsulating CNOs are applicable in the field of batteries or supercapacitors.
Chloroperoxidase production by Caldariomyces fumago biofilms
Authors: Huster Manuel , Müller‐Renno Christine , Ziegler Christiane , Schlegel Christin , Ulber Roland , Muffler Kai
Published: September 2015

Chloroperoxidase (CPO) is a versatile enzyme, which is secreted by the marine fungus Caldariomyces fumago (Leptoxyphium fumago). However, the application of the enzyme is hampered by its high price, which is due to the costly, labor‐intensive purification process. One challenge of the downstream process is the removal of a coproduced black pigment that forms a complex with the active enzyme. While strain development can be considered as an option to reduce the synthesis of the interfering pigment, the metabolism of the microorganism can be altered alternatively by using the biofilm growth mode of the fungus. The aim of this study was to reduce pigment formation during CPO synthesis. We investigated for the first time CPO production during C. fumago biofilm growth initiated through the presence of different microstructured stainless steel surfaces (material number: 1.4571; AISI 316Ti). CPO production by C. fumago was similar when grown as a biofilm or in suspension, whereas pigment formation was drastically reduced by cells grown on moderately structured surfaces (Ra = 0.13 ± 0.02 μm). The possibilities of biofilm growth for changing cell properties and for continuous fermentation are discussed.
Effect of non‐moment braced frame seismic deformations on buckling‐restrained brace end connection behavior: Theoretical analysis and subassemblage tests
Authors: Zhao Junxian , Lin Fuxiong , Wang Zhan
Published: September 2015

In‐plane buckling‐restrained brace (BRB) end rotation induced by frame action is a commonly observed phenomenon in buckling‐restrained braced frames (BRBFs). However, its effect on BRB end connection behavior has not yet been clear. In this study, four BRB end deformation modes for quick determination of end rotational demand are proposed for non‐moment BRBF considering different BRB arrangements, installing story of BRBs, and boundary condition of corner gussets connected with column base. Key factors affecting BRB end rotation and flexural moments are examined theoretically by parametric analysis. Subassemblage tests of seven BRB specimens under horizontal cyclic loading were conducted by adopting two loading frames to impose the expected BRB end deformations. It shows that BRB end rotation subjected BRB ends to significant flexural moments, leading to premature yielding of BRB ends or even tendency of end zone buckling. The deformation modes, the flexural rigidity of BRB ends, and the initial geometric imperfections of BRBs were found to have significant influence on BRB end connection behavior. The triggering moment induced by BRB end rotation was the main contributor to end flexural moment. However, the moment amplification effect induced by flexure of BRB end zones became prominent especially for small flexural rigidity of BRB ends. Implications and future research needs for design of BRB end connections are provided finally based on the theoretical and experimental results. Copyright © 2015 John Wiley & Sons, Ltd.
Simplified macro‐model for infill masonry walls considering the out‐of‐plane behaviour
Authors: Furtado André , Rodrigues Hugo , Arêde António , Varum Humberto
Published: September 2015

One of the main challenges in earthquake risk mitigation is the assessment of existing buildings not designed according to modern codes and the development of effective techniques to strengthen these structures. Particular attention should be given to RC frame structures with masonry infill panels, as demonstrated by their poor performance in recent earthquakes in Europe. Understanding the seismic behaviour of masonry‐infilled RC frames presents one of the most difficult problems in structural engineering. Analytical tools to evaluate infill–frame interaction and the failure mechanisms need to be further studied. This research intends to develop a simplified macro‐model that takes into account the out‐of‐plane behaviour of the infill panels and the corresponding in‐plane and out‐of‐plane interaction when subjected to seismic loadings. Finally, a vulnerability assessment of an RC building will be performed in order to evaluate the influence of the out‐of‐plane consideration in the building response. Copyright © 2015 John Wiley & Sons, Ltd.
A 400‐year isotopic record of seabird response to eastern tropical Pacific productivity
Authors: Conroy Jessica L , Collins Aaron F , Overpeck Jonathan T , Bush Mark B , Cole Julia E , Anderson David J
Published: September 2015

Seabirds play an important role in coastal environments, serving as key indicators of marine ecosystem variability as well as biovectors that influence terrestrial productivity and carbon storage. Long‐term estimates of seabird populations remain rare, but lakes that support large seabird populations in their watersheds can archive a history of seabird activity in their sediment records. Here we present a seabird guano‐influenced sediment record from Genovesa Crater Lake, Galápagos Islands, home to the world's largest reported colony of red‐footed boobies (Sula sula) and smaller populations of other species. Influx of seabird guano into Genovesa Crater Lake produces high sedimentary δ15N values, and temporal variability in sediment δ15N primarily reflects changes in guano influx through time. Two abrupt increases in sedimentary δ15N occurred at 1835 AD and 1965 AD, and variance increased following the 1965 AD shift. The largest of these abrupt shifts at 1835 AD coincided, within age model error, with an abrupt increase in marine productivity indicators in sediment records off the coast of Perú and Chile. In the latter part of the twentieth century, δ15N values increased during periods of higher landings of Peruvian anchoveta and sardines. We hypothesise that seabird presence and activity on Genovesa increased during periods of higher regional marine productivity. Enhanced variance in Genovesa δ15N following the 1965 AD shift may reflect a modern population more susceptible to climate and environmental variability than at any other time in the last 400 years.
Differential involvement of cortical and cerebellar areas using dominant and nondominant hands: An FMRI study
Authors: Alahmadi Adnan A.S. , Pardini Matteo , Samson Rebecca S. , D'Angelo Egidio , Friston Karl J. , Toosy Ahmed T. , Gandini Wheeler‐Kingshott Claudia A.M.
Published: September 2015

Motor fMRI studies, comparing dominant (DH) and nondominant (NDH) hand activations have reported mixed findings, especially for the extent of ipsilateral (IL) activations and their relationship with task complexity. To date, no study has directly compared DH and NDH activations using an event‐related visually guided dynamic power‐grip paradigm with parametric (three) forces (GF) in healthy right‐handed subjects. We implemented a hierarchical statistical approach aimed to: (i) identify the main effect networks engaged when using either hand; (ii) characterise DH/NDH responses at different GFs; (iii) assess contralateral (CL)/IL‐specific and hemisphere‐specific activations. Beyond confirming previously reported results, this study demonstrated that increasing GF has an effect on motor response that is contextualised also by the use of DH or NDH. Linear analysis revealed increased activations in sensorimotor areas, with additional increased recruitments of subcortical and cerebellar areas when using the NDH. When looking at CL/IL‐specific activations, CL sensorimotor areas and IL cerebellum were activated with both hands. When performing the task with the NDH, several areas were also recruited including the CL cerebellum. Finally, there were hand‐side‐independent activations of nonmotor‐specific areas in the right and left hemispheres, with the right hemisphere being involved more extensively in sensori‐motor integration through associative areas while the left hemisphere showing greater activation at higher GF. This study shows that the functional networks subtending DH/NDH power‐grip visuomotor functions are qualitatively and quantitatively distinct and this should be taken into consideration when performing fMRI studies, particularly when planning interventions in patients with specific impairments. Hum Brain Mapp 36:5079–5100, 2015. © 2015 Wiley Periodicals, Inc.
Spatiotemporal patterns of cortical fiber density in developing infants, and their relationship with cortical thickness
Authors: Li Gang , Liu Tianming , Ni Dong , Lin Weili , Gilmore John H. , Shen Dinggang
Published: September 2015

The intrinsic relationship between the convoluted cortical folding and the underlying complex whiter matter fiber connections has received increasing attention in current neuroscience studies. Recently, the axonal pushing hypothesis of cortical folding has been proposed to explain the finding that the axonal fibers (derived from diffusion tensor images) connecting to gyri are significantly denser than those connecting to sulci in both adult human and non‐human primate brains. However, it is still unclear about the spatiotemporal patterns of the fiber density on the cortical surface of the developing infant brains from birth to 2 years of age, which is the most dynamic phase of postnatal brain development. In this paper, for the first time, we systemically characterized the spatial distributions and longitudinal developmental trajectories of the cortical fiber density in the first 2 postnatal years, via joint analysis of longitudinal structural and diffusion tensor imaging from 33 healthy infants. We found that the cortical fiber density increases dramatically in the first year and then keeps relatively stable in the second year. Moreover, we revealed that the cortical fiber density on gyral regions was significantly higher at 0, 1, and 2 years of age than that on sulcal regions in the frontal, temporal, and parietal lobes. Meanwhile, the cortical fiber density was strongly positively correlated with cortical thickness at several three‐hinge junction regions of gyri. These results significantly advanced our understanding of the intrinsic relationship between the cortical folding, cortical thickness and axonal wiring during early postnatal stages. Hum Brain Mapp 36:5183–5195, 2015. © 2015 Wiley Periodicals, Inc.
Neural responses to kindness and malevolence differ in illness and recovery in women with anorexia nervosa
Authors: McAdams Carrie J. , Lohrenz Terry , Montague P. Read
Published: September 2015

In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long‐term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently‐ill and weight‐recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently‐ill subjects. Next, using a whole‐brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self‐report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception. Hum Brain Mapp 36:5207–5219, 2015. © 2015 Wiley Periodicals, Inc.
Evidence that smooth pursuit velocity, not eye position, modulates alpha and beta oscillations in human middle temporal cortex
Authors: Dunkley Benjamin T. , Freeman Tom C.A. , Muthukumaraswamy Suresh D. , Singh Krish D.
Published: September 2015

Suppression of 5–25 Hz oscillations have been observed in MT+ during pursuit eye movements, suggesting oscillations that play a role in oculomotor control and/or the integration of extraretinal signals during pursuit. The amplitude of these rhythms appears to covary with head‐centered eye position, but an alternative is that they depend on a velocity signal that lags the movement of the eyes. To investigate, we explored how alpha and beta amplitude changes related to ongoing eye movement depended on pursuit at different eccentricities. The results revealed largely identical patterns of modulation in the alpha and beta amplitude, irrespective of the eccentricity at which the pursuit eye movement was performed. The signals we measured therefore do not depend on head‐centered position. A second experiment was designed to investigate whether the alpha and beta oscillations depended on the direction of pursuit, as opposed to just speed. We found no evidence that alpha or beta oscillations depended on direction, but there was a significant effect of eye speed on the magnitude of the beta suppression. This suggests distinct functional roles for alpha and beta suppression in pursuit behavior. Hum Brain Mapp 36:5220–5232, 2015. © 2015 Wiley Periodicals, Inc.
Distribution and immunotoxicity by intravenous injection of iron nanoparticles in a murine model
Authors: Park Eun‐Jung , Oh Seung Yun , Kim Younghun , Yoon Cheolho , Lee Byoung‐Seok , Kim Sang Doo , Kim Jong Sung
Published: September 2015

With the increased application of iron oxide nanoparticles (FeNPs) for biomedical imaging purposes, concerns regarding the onset of the unexpected adverse health effects following exposure have been rapidly raised. In this study, we investigated the tissue distribution and immunotoxicity of FeNPs (2 and 4 mg kg–1) over time (2, 4 and 13 weeks) after single intravenous injection. At 13 weeks after a single injection, the iron levels increased in all measured tissues compared to the control, and iron accumulation was notable in the liver, spleen and thymus. These changes were accompanied by changes in levels of redox reaction‐related elements, including copper, manganese, zinc and cobalt. In addition, as compared to the control, the number of white blood cells and percentage of neutrophils significantly increased in the treated groups, and the interleukin‐8 secretion and lactate dehydrogenase release were clearly elevated in the treated groups along with enhanced expressions of chemotaxis‐related proteins. However, expression of antigen presenting related proteins attenuated following accumulation of FeNPs. Taken together, we suggest that FeNPs may primarily induce toxicity in the liver and immune system, and immunotoxicological evaluation should be considered to predict adverse health effects following exposure to NPs. Copyright © 2015 John Wiley & Sons, Ltd.
Porous poly (D,L‐lactide‐co‐glycolide) acid/biosilicate® composite scaffolds for bone tissue engineering
Authors: Kido Hueliton W. , Brassolatti Patricia , Tim Carla R. , Gabbai‐Armelin Paulo R. , Magri Angela M.P. , Fernandes Kelly R. , Bossini Paulo S. , Parizotto Nivaldo A. , Crovace Murilo C. , Malavazi Iran , da Cunha Anderson F. , Plepis Ana M.G. , Anibal Fernanda F. , Rennó Ana C.M.
Published: September 2015

This study evaluated the effects of the Biosilicate® and poly (D,L‐lactic‐co‐glycolic) acid composites on bone repair in a tibial bone defect model in rats by means of using histological evaluation (histopathological and morphometric analysis) and gene expression analysis. Eighty male Wistar rats (12 weeks old, weighing ±300 g) were randomly divided into two groups: Biosilicate® group (BG) and Biosilicate®/PLGA group (BG/PLGA). Each group was euthanized at 3, 7, 14, and 21 days after surgery (n = 10 animals per time point). The main findings showed that the incorporation of PLGA into BG had a significant effect on the morphological structure of the material, accelerating mass loss, decreasing the pH and increasing the calcium release. Furthermore, histologic analysis revealed that the BG/PLGA showed increased material degradation, accompanied by higher bone formation compared to BG, after 21 days of implantation. In addition, qRT‐PCR analysis showed that BG/PLGA induced an upregulation of the osteogenic genes related to BMP4, Runx2, ALP, and OC. These results show that the present BG/PLGA composite may be used as a bone graft for inducing bone repair. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 63–71, 2017.
RNA‐Seq Reveals Acute Manganese Exposure Increases Endoplasmic Reticulum Related and Lipocalin mRNAs in Caenorhabditis elegans
Authors: Rudgalvyte Martina , Peltonen Juhani , Lakso Merja , Nass Richard , Wong Garry
Published: September 2015

Manganese (Mn) is an essential nutrient; nonetheless, excessive amounts can accumulate in brain tissues causing manganism, a severe neurological condition. Previous studies have suggested oxidative stress, mitochondria dysfunction, and impaired metabolism pathways as routes for Mn toxicity. Here, we used the nematode Caenorhabditis elegans to analyze gene expression changes after acute Mn exposure using RNA‐Seq. L1 stage animals were exposed to 50 mM MnCl2 for 30 min and analyzed at L4. We identified 746 up‐ and 1828 downregulated genes (FDR corrected p < 0.05; two‐fold change) that included endoplasmic reticulum related abu and fkb family genes, as well as six of seven lipocalin‐related (lpr) family members. These were also verified by qRT‐PCR. RNA interference of lpr‐5 showed a dramatic increase in whole body vulnerability to Mn exposure. Our studies demonstrate that Mn exposure alters gene transcriptional levels in different cell stress pathways that may ultimately contribute to its toxic effects.
Structure Elucidation of a Complex Faldaprevir‐(±)‐α‐Tocopherol Addition Product Reveals Reactivity of Common Excipient Vitamin E‐TPGS
Authors: Gonnella Nina C. , Rodriguez Shirley A. , Pennino Scott , Norwood Daniel
Published: September 2015

Vitamin E‐TPGS (d‐α‐tocopheryl polyethylene glycol succinate) is a common excipient used in drug formulations. This excipient is formed by esterification of Vitamin E succinate with polyethylene glycol. As part of an oral formulation for active pharmaceutical ingredient (API) Faldaprevir, Vitamin E‐TPGS was found to decompose under ambient conditions producing free (±)‐α‐Tocopherol which subsequently formed an adduct composed of α‐Tocopherol and the API. The addition product was isolated using liquid chromatography with collections onto solid‐phase extraction cartridges, and full structure elucidation was achieved using mass spectrometry and nuclear magnetic resonance spectroscopy. The results revealed a regioselective addition of α‐Tocopherol to the API that likely occurs through the formation of a stabilized ortho‐quinone methide intermediate. This finding demonstrates the propensity of the common excipient (Vitamin E‐TPGS) to generate chemically active intermediates that may react with formulation ingredients.
Amination of Malononitrile Dimer to Amidines: Synthesis of 6‐aminopyrimidines
Authors: Elkanzi N. A. A. , Aly Ashraf A. , Shawky Ahmed M. , El‐Sheref Essmat M. , Morsy Nesrin M. , El‐Reedy Ahmed A. M.
Published: September 2015

Reactions of amidines with malononitrile dimer in DMF and catalyzed with piperidine are reported. The reaction occurred via amination process followed by cyclization to give racemic 6‐aminopyrimidine compounds. The reaction mechanism was discussed. The structure of products was elucidated by mass spectrometry, IR and NMR spectra together with elemental analyses.
A Convenient and Facile Hantzsch Synthesis of Aryl Imidazo[1,2‐b]Isoxazolyl‐N‐aryl Thiazol Amines
Authors: Rajanarendar E. , Thirupathaiah K. , Ramakrishna S. , Nagaraju D.
Published: September 2015

The Hantzsch synthesis of novel aryl imidazo[1,2‐b]isoxazolyl‐N‐aryl thiazol amines 5 analogues were described. Reaction of 3‐aminoisoxazole 1 with substituted phenacyl bromides 2 in dry ethanol afforded the corresponding 6‐methyl‐3‐arylimidazo[1,2‐b]isoxazoles 3 in good yields. Compounds 3 on reaction with chloroacetyl chloride in 1,4‐dioxane furnished the corresponding 2‐chloro‐1‐(6‐methyl‐3‐arylimidazo[1,2‐b]isoxazol‐2‐yl)ethanones 4. Compounds 4 on heating with N‐aryl thioureas in an oil bath underwent cyclization to afford the title compounds viz., imidazo[1,2‐b]isoxazolyl‐N‐aryl thiazol amines 5 in moderate to good yields by Hantzsch synthesis.
Where we've been, where we are, and where we are going: A 35‐year perspective on healthcare risk management
Authors: Carroll Roberta L.
Published: September 2015

In celebration of ASHRM's 35‐year anniversary, this article will explore the journey of healthcare risk management and the professionals practicing within its discipline over time and project the future of both the discipline and the ­profession.
Business resilience: Reframing healthcare risk management
Authors: Simeone Cynthia L.
Published: September 2015

The responsibility of risk management in healthcare is fractured, with multiple stakeholders. Most hospitals and healthcare systems do not have a fully integrated risk management system that spans the entire organizational and operational structure for the delivery of key services. This article provides insight toward utilizing a comprehensive Business Resilience program and associated methodology to understand and manage organizational risk leading to organizational effectiveness and operational efficiencies, with the fringe benefit of realizing sustainable operational capability during adverse conditions.
Comparison of NCEP‐NCAR and ERA‐Interim over Australia
Authors: Fu Guobin , Charles Stephen P. , Timbal Bertrand , Jovanovic Branislava , Ouyang Fen
Published: September 2015

This study compares observations of 22 climate variables [rainfall, minimum and maximum temperature, mean sea level pressure (MSLP), and air temperature, geopotential heights, relative and specific humidity, and u‐wind and v‐winds at 500, 700 and 850 hPa] over Australia with NCEP‐NCAR (National Centers for Environmental Prediction‐National Center for Atmospheric Research) and ERA‐Interim, two most often used reanalysis products. The results indicate that both NCEP‐NCAR and ERA‐Interim generally reproduce the observed spatial patterns of long‐term mean annual rainfall, daily maximum/minimum temperature and MSLP, the monthly distribution (annual cycle) of rainfall and temperature, although temperature is generally better simulated than rainfall and ERA‐Interim shows an overall better performance than NCEP‐NCAR in term of continental scale. In term of linear trends, both NCEP‐NCAR and ERA‐Interim simulate observed trend signs in some regions, but not in others, and the spatial distributions of temperature trends are generally not as well simulated as that of annual rainfall for both NCEP‐NCAR and ERA‐Interim. In addition, NCEP‐NCAR and ERA‐Interim show similar spatial patterns of annual mean air temperature, geopotential heights, humidity and winds. This implies that studies using NCEP‐NCAR data could also make use of ERA‐Interim to explore the range of uncertainties for the regions and climate variables where NCEP‐NCAR and ERA‐Interim show differences. This conclusion may also apply to regions other than Australia. For example, the different trend signs of MSLP between NCEP‐NCAR and ERA‐Interim could present a scientific challenging for climatic change studies using MSLP trends, and the split between large‐scale and convective rainfall would also have merits globally to understand if the differences between the two reanalysis data sets are global or if we see convergence on key areas, such as tropices and frontal systems.
Use of an IL1‐receptor antagonist to prevent the progression of tendinopathy in a rat model
Authors: Berkoff David J. , Kallianos Steven A. , Eskildsen Scott M. , Weinhold Paul S.
Published: September 2015

This study evaluated if inhibiting IL1‐β activity with an IL1‐receptor antagonist (IL1‐RA) will prevent pathologic changes commonly seen in tendinopathy. Thirty‐six Sprague–Dawley retired‐breeder rats were divided into three groups having weekly bilateral patellar tendon injections: CON (0.1 ml Saline), CAR (0.1 ml 2% carrageenan), IL1‐RA (0.1 ml 2% CAR plus 0.94 mg of the IL1‐RA, 2.5 mg/kg). Carrageenan was used to establish tendinopathy in two groups due to its ability to develop tendinopathy in prior studies. Animals were euthanized 3 weeks after initial injection. The CAR group demonstrated significantly (p < 0.05) shorter tendon lengths (8.61 ± 0.38 mm) relative to CON (8.94 ± 0.38 mm) that was prevented in the IL1‐RA (9.02 ± 0.30 mm) as well as significantly increased collagenase activity in the CAR (0.061 ± 0.043) compared to CON (0.027 ± 0.015) (p<  0.05). By histological evaluation, the CAR group demonstrated significantly greater inflammation than IL1‐RA, and CON (p < 0.05). CAR showed a trend for increased cross‐sectional area relative to CON that was absent in the IL1‐RA. IL1‐RA can effectively inhibit the development of mechanical, chemical, and histologic changes seen with carrageenan‐induced tendonitis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:616–622, 2016.
Effect of soil drying on mucilage exudation and its water repellency: a new method to collect mucilage
Authors: Ahmed Mutez A. , Holz Maire , Woche Susanne K. , Bachmann Jörg , Carminati Andrea
Published: September 2015

Despite the importance of mucilage for soil–plant relations, little is known about the effect of soil drying on mucilage exudation. We introduce a method to collect mucilage from maize growing in wet and dry soils. Mucilage was collected from brace roots. The amount of mucilage exuded did not change with soil water content and transpiration rate. Mucilage exuded in dry soils had a higher degree of hydrophobicity, suggesting that the wetting properties of mucilage change in response to soil drying.
Developing a carob‐based milk beverage using different varieties of carob pods and two roasting treatments and assessing their effect on quality characteristics
Authors: Srour Nadine , Daroub Hamza , Toufeili Imad , Olabi Ammar
Published: September 2015

BACKGROUND

This work aimed at formulating a carob‐based milk beverage and assessing its chemical and sensory properties. Six varieties of carob pods, each processed into roasted and unroasted powders, were used to develop 12 prototypes of the beverage. Chemical and physico‐chemical analyses (moisture, ash, fibre, protein, sugars, total‐phenolics, total‐antioxidants, water activity and colour) and sensory tests were conducted.

RESULTS

The variety of carob pod had a significant effect on all chemical variables in carob powders (P < 0.01), except for sugars, and when incorporated in the beverage, on moisture, total phenolics, total antioxidant activity and colour parameters (L, a, b; P‐values < 0.001). Roasting treatment significantly increased fibre, total phenolics, total antioxidant activity (P‐values < 0.001), fructose, glucose (P‐values < 0.05), and a‐value levels (P < 0.01), significantly lowered moisture (P < 0.05), water activity, L‐ and b‐values (P‐values < 0.001) in carob powders; and significantly increased the beverage's total phenolics, a‐value (P‐values < 0.001) and total antioxidant activity (P < 0.01). Roasting treatment significantly increased the beverage's acceptability ratings. Beverages formulated with roasted carob powder had higher ratings for level of residue, colour, caramel odour, mocha odour and flavour, roasted coffee odour and flavour, viscosity mouthfeel and bitter aftertaste. Principal component analysis was conducted; PC1 and PC2 separated attributes according to roasting treatment and variety of carob pods, respectively.

CONCLUSION

The use of Akkari roasted and Baladi Ikleem el Kharoob roasted to formulate a carob‐based milk beverage is recommended. © 2015 Society of Chemical Industry
In ovo administration of copper nanoparticles and copper sulfate positively influences chicken performance
Authors: Mroczek‐Sosnowska Natalia , Łukasiewicz Monika , Wnuk Agnieszka , Sawosz Ewa , Niemiec Jan , Skot Abdullah , Jaworski Sławomir , Chwalibog André
Published: September 2015

BACKGROUND

Copper (Cu) is a key trace mineral involved in a variety of physiological processes, and is commonly used in poultry production. However, regardless of the inclusion level the majority of Cu is excreted with poultry faeces. We hypothesise that in ovo administration will allow for better utilisation of Cu during embryo development than when supplied post‐natally with feed to growing chickens. Thus, the objective of this study was to evaluate effects of in ovo administration of NanoCu and copper sulfate (CuSO4) on broiler chicken performance.

RESULTS

The study showed the positive influences of Cu nanoparticles and CuSO4 on broiler chickens performance. Body weight, at the end of the rearing period (day 42) was significantly higher in NanoCu (2206 g) and CuSO4 (2402 g) groups compared to the control group (2000 g). Both treatment groups had significantly lower feed conversion rate and mortality, and higher percentage of breast and leg muscles in the carcass versus control.

CONCLUSION

The in ovo application of Cu colloids may ensure an efficient penetration of Cu into the embryonic tissue with long lasting effects on postnatal growth. The method may provide a successful alternative to using Cu as a feed additive. © 2015 Society of Chemical Industry
Nutrition recommendations and science: next parallel steps
Authors: Fogelholm Mikael
Published: September 2015

This article examines nutrition recommendations in relation to developments in nutrition science. Combining data on the genome, metabolome and microbiota is likely to open possibilities for personalized nutrition planning, but we are still far from practical applications. However, even these new steps are unlikely to challenge the role and importance of population‐based nutrition recommendations as a tool to promote dietary patterns, policies and public health. Developments in science could help in deriving more benefits from nutrition recommendations. For instance, improved accuracy of dietary intake assessment is needed both for surveillance and for understanding the quantitative interplay between diet and health. Applying metabolomics together with food diaries or questionnaires, and also modern technologies such as digital photography, are potentially interesting methods in this respect. Research on consumer behaviour, attitudes and policy interventions, such as taxation of unhealthy foods and nutrition labelling, are needed to gain more insight into how to change eating behaviour for better health at the population level. © 2015 Society of Chemical Industry
Asbestos exposure and laryngeal cancer mortality
Authors: Peng Wen‐jia , Mi Jing , Jiang Yu‐hong
Published: September 2015

Objectives/Hypothesis

Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma. However, the link between asbestos exposure and other malignancies was not confirmed. The aim of the current meta‐analysis was to provide a summary measure of risk for laryngeal cancer associated with occupational asbestos exposure.

Study Design

Systematic review and meta‐analysis.

Methods

Electronic databases were searched for studies characterizing the association between asbestos and laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence interval (CI) of each study was combined using a fixed or random effect model.

Results

Significantly increased SMR for laryngeal cancer was observed when subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45‐1.97, P < .001), with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I2 = 0.0%). Effect estimates were larger for cohorts controlling for male subjects, Europe and Oceania, mining and textile industries, exposure to crocidolite, long study follow‐up (>25 years), and SMR for lung cancer > 2.0. Publication bias was not detect by Begg test (P = .910) and Egger test (P = .340).

Conclusions

Our study supports the association of exposure to asbestos with an increased risk of laryngeal cancer mortality among male workers.

Level of Evidence

NA Laryngoscope, 126:1169–1174, 2016