bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain
Authors: Tie Feng , Banerjee Rakhee , Fu Chen , Stratton Carl A. , Fang Ming , Harte Peter J.
Published: January 2016

Significance

The Polycomb protein (PC) is well known for its role in transcriptional silencing and binding to trimethylated histone H3 Lys27 (H3K27me3). We report here that PC inhibits the histone acetyltransferase (HAT) activity of CREB-binding protein (CBP). PC interacts directly with the CBP HAT domain, binding to its autoregulatory loop, whose autoacetylation greatly enhances enzyme activity. PC binding inhibits histone H3 acetylation. Interestingly, CBP autoacetylation impairs PC binding in vitro, and PC is preferentially associated with unacetylated CBP in vivo. Altering PC levels in vivo alters the acetylated H3K27 (H3K27ac) level in a predictable manner. PC inhibition of CBP HAT activity at enhancers and promoters with paused RNA polymerase II may affect regulation of both repressed and active genes.
Spatial and temporal dynamics of Atlantic menhaden (Brevoortia tyrannus) recruitment in the Northwest Atlantic Ocean
Authors: Buchheister Andre , Miller Thomas J. , Houde Edward D. , Secor David H. , Latour Robert J.
Published: January 2016

Atlantic menhaden, Brevoortia tyrannus, is an abundant, schooling pelagic fish that is widely distributed in the coastal Northwest Atlantic. It supports the largest single-species fishery by volume on the east coast of the United States. However, relatively little is known about factors that control recruitment, and its stock–recruitment relationship is poorly defined. Atlantic menhaden is managed as a single unit stock, but fisheries and environmental variables likely act regionally on recruitments. To better understand spatial and temporal variability in recruitment, fishery-independent time-series (1959–2013) of young-of-year (YOY) abundance indices from the Mid-Atlantic to Southern New England (SNE) were analysed using dynamic factor analysis and generalized additive models. Recruitment time-series demonstrated low-frequency variability and the analyses identified two broad geographical groupings, the Chesapeake Bay (CB) and SNE. Each of these two regions exhibited changes in YOY abundance and different periods of relatively high YOY abundance that were inversely related to each other; CB indices were highest from ca. 1971 to 1991, whereas SNE indices were high from ca. 1995 to 2005. We tested for effects of climatic, environmental, biological, and fishing-related variables that have been documented or hypothesized to influence stock productivity. A broad-scale indicator of climate, the Atlantic Multidecadal Oscillation, was the best single predictor of coast-wide recruitment patterns, and had opposing effects on the CB and SNE regions. Underlying mechanisms of spatial and interannual variability in recruitment likely derive from interactions among climatology, larval transport, adult menhaden distribution, and habitat suitability. The identified regional patterns and climatic effects have implications for the stock assessment of Atlantic menhaden, particularly given the geographically constrained nature of the existing fishery and the climatic oscillations characteristic of the coastal ocean.
Role of the Infectious Disease Consultant in Management of Patients With Tuberculosis-Associated Ocular Inflammation
Authors: Conant Marjorie M. , Vrasich Chuck R. , Wongskhaluang Jeff V. , Ferenchak Kevin , Asano Matthew K. , Becker Norbert , DeMarais Patricia
Published: January 2016

Background.  Tuberculosis is a disease with continued worldwide prevalence, morbidity, and mortality. Tuberculosis-associated ocular inflammation (TB-AOI) is a manifestation that can occur with pulmonary or extrapulmonary TB. Evaluation of these ocular presentations and treatment in the United States are limited. Our objective was to describe cases in an urban area and assess the role of the infectious diseases specialist in managing these complex patients.

Methods.  We performed a retrospective case series of all patients referred to our infectious disease clinic for presumed TB-AOI from 2005 through 2013. Patients with ocular inflammation were determined to have presumed TB-AOI based on clinical presentation with correlative positive tuberculin skin test and/or QuantiFERON-TB Gold. Attempts were made to exclude other diagnoses. Data were collected and analyzed with respect to demographics, ocular manifestations, and treatment.

Results.  Sixty eyes of 42 patients were included in the study; anterior uveitis was the most common site of involvement. The median age was 46 years, and 33 patients (79%) were foreign born. Forty patients (95%) received a course of antituberculous therapy with 38% experiencing treatment-related side effects. A 6-month duration was recommended in 78% cases. There was improvement or stability of the vision in 42 eyes (74%) of those treated.

Conclusions.  Ocular involvement is an uncommon but important manifestation of TB. Our data further characterize TB-AOI cases in the United States. Treatment provides significant benefit to properly selected patients. A multidisciplinary approach, with care provided by ophthalmology and infectious disease providers, should be used to allow for the most efficacious treatment.
Differential Suppression of Spontaneous and Noxious-evoked Somatosensory Cortical Activity by Isoflurane in the Neonatal Rat
Authors: Chang Pi-shan , Walker Suellen M. , Fitzgerald Maria
Published: January 2016

AbstractAbstract

Extracellular somatosensory cortex field potentials evoked by hind paw C-fiber electrical stimulation were resistant to isoflurane compared with spontaneous activity in neonatal rat. Surgical hind paw incision enhanced the resistance of noxious-evoked responses to isoflurane, an effect that declined with age, indicating critical age-dependent differences in anesthetic suppression of cortical nociceptive activity.

Background

The effect of neonatal anesthesia and pain on the developing brain is of considerable clinical importance, but few studies have evaluated noxious surgical input to the infant brain under anesthesia. Herein, the authors tested the effect of increasing isoflurane concentration on spontaneous and evoked nociceptive activity in the somatosensory cortex of rats at different postnatal ages.

Methods

Intracortical extracellular field potentials evoked by hind paw C-fiber electrical stimulation were recorded in the rat somatosensory cortex at postnatal day (P) 7, P14, P21, and P30 during isoflurane anesthesia (n = 7 per group). The amplitudes of evoked potentials and the energies of evoked oscillations (1 to 100 Hz over 3 s) were measured after equilibration at 1.5% isoflurane and during step increases in inspired isoflurane. Responses during and after plantar hind paw incision were compared at P7 and P30 (n = 6 per group).

Results

At P7, cortical activity was silent at 1.5% isoflurane but noxious-evoked potentials decreased only gradually in amplitude and energy with step increases in isoflurane. The resistance of noxious-evoked potentials to isoflurane at P7 was significantly enhanced after surgical hind paw incision (69 ± 16% vs. 6 ± 1% in nonincised animals at maximum inspired isoflurane). This resistance was age dependent; at P14 to P30, noxious-evoked responses decreased sharply with increasing isoflurane (step 3 [4%] P7: 50 ± 9%, P30: 4 ± 1% of baseline). Hind paw incision at P30 sensitized noxious-evoked potentials, but this was suppressed by higher isoflurane concentrations.

Conclusions

Despite suppression of spontaneous activity, cortical-evoked potentials are more resistant to isoflurane in young rats and are further sensitized by surgical injury.
Sonoelastography of Breast Lymphoma
Authors: Sousaris Nicholas , Barr Richard G.
Published: January 2016

Breast lymphomas only account for approximately 0.15% of malignant breast carcinomas. Half of these are primary lymphomas, and the other half are metastatic to the breast. Ultrasound elastography has been proven to aid in the diagnosis of breast lesions as malignant or benign, with malignancy appearing stiffer compared with normal breast tissue. However, in this study, we review the findings of breast lymphoma on strain and shear wave ultrasonography. Lymphoma appears drastically different on sonoelastography than primary breast cancers, and it could easily be interpreted as benign. Therefore, the unique imaging findings in addition to the patient's clinical history are important in differentiating lymphoma of the breast from other possible diagnoses.
Salt screening and characterization of ciprofloxacin
Authors: Zhang Guoshun , Zhang Li , Yang Dezhi , Zhang Na , He Lan , Du Guanhua , Lu Yang
Published: January 2016

With the aim of improving the solubility of ciprofloxacin, polybasic organic acids were utilized to react with ciprofloxacin in different stoichiometric proportions. The use of the solvent drop grinding (SDG) method, as well as the solvent evaporation method, resulted in the crystalline salts ciprofloxacin/fumaric acid (1:1, 2:1), ciprofloxacin/maleic acid (1:1) and ciprofloxacin/citric acid (2:1). The solubilities of these salts in pure water (pH 7.0) were determined using high-performance liquid chromatography (HPLC) at 310 K, with the salts showing considerably greater solubility than ciprofloxacin itself and, interestingly, ciprofloxacin/fumaric acid (2:1) being more soluble than ciprofloxacin/fumaric acid (1:1). Intrigued by this phenomenon, we undertook a comparison of the crystal structures of the salts: the three-dimensional sandwich-like structure observed in the 2:1 salt indicates that the preferred stacking may be a factor in increasing the solubility of ciprofloxacin.
Experimental and theoretical charge-density analysis of 1,4-bis(5-hexyl-2-thienyl)butane-1,4-dione: applications of a virtual-atom model
Authors: Ahmed Maqsood , Nassour Ayoub , Noureen Sajida , Lecomte Claude , Jelsch Christian
Published: January 2016

The experimental and theoretical charge densities of 1,4-bis(5-hexyl-2-thienyl)butane-1,4-dione, a precursor in the synthesis of thiophene-based semiconductors and organic solar cells, are presented. A dummy bond charges spherical atom model is applied besides the multipolar atom model. The results show that the dummy bond charges model is accurate enough to calculate electrostatic-derived properties which are comparable with those obtained by the multipolar atom model. The refinement statistics and the residual electron density values are found to be intermediate between the independent atom and the multipolar formalisms.
Charge distribution as a tool to investigate structural details. IV. A new route to heteroligand polyhedra
Authors: Nespolo Massimo
Published: January 2016

A new route to apply the charge distribution (CHARDI) method to structures based on heteroligand coordination polyhedra is presented. The previous algorithm used scale factors computed in an iterative way based on the assumption (which turned out to be not always correct) that a real over–under bonding effect affects mainly the anionic charges of each single anion, without grossly modifying the total charge of each type of anion. The new, more general approach is not based on anya prioriassumption but treats separately the homoligand sub-polyhedra and attributes to each type of atom a fraction of the charge of the atom coordinated to it, computed in a self-consistent iterative way. The distinction between the bonding and non-bonding contact is also redefined in terms of the mean fictive ionic radii (MEFIR), without the need of an empirical parameter, used in the previous algorithm. CHARDI equations are generalized in terms of the new approach and a series of examples is presented.
Electron density, disorder and polymorphism: high-resolution diffraction studies of the highly polymorphic neuralgic drug carbamazepine
Authors: Sovago Ioana , Gutmann Matthias J. , Senn Hans Martin , Thomas Lynne H. , Wilson Chick C. , Farrugia Louis J.
Published: January 2016

Analysis of neutron and high-resolution X-ray diffraction data on form (III) of carbamazepine at 100 K using the atoms in molecules (AIM) topological approach afforded excellent agreement between the experimental results and theoretical densities from the optimized gas-phase structure and from multipole modelling of static theoretical structure factors. The charge density analysis provides experimental confirmation of the partially localized π-bonding suggested by the conventional structural formula, but the evidence for any significant C—N π bonding is not strong. Hirshfeld atom refinement (HAR) gives H atom positional and anisotropic displacement parameters that agree very well with the neutron parameters. X-ray and neutron diffraction data on the dihydrate of carbemazepine strongly indicate a disordered orthorhombic crystal structure in the space groupCmca, rather than a monoclinic crystal structure in space groupP21/c. This disorder in the dihydrate structure has implications for both experimental and theoretical studies of polymorphism.
Determining europium compositional fluctuations in partially stabilized zirconia nanopowders: a non-line-broadening-based method
Authors: Marin Riccardo , Sponchia Gabriele , Back Michele , Riello Pietro
Published: January 2016

A method is reported for assessing the compositional fluctuations in a ceramic sample, based only on the determination of the crystalline lattice parameters. Pure tetragonal phase partially stabilized zirconia powders are synthesized through the co-precipitation method by incorporating 4% Eu3+. The powder is subjected to compression cycles to promote the tetragonal-to-monoclinic transformation. The Rietveld analysis of the X-ray powder diffraction patterns, recorded after each compression cycle, gives information about the lattice parameters and monoclinic phase content. The determination of europium content in the residual tetragonal phase is accomplished considering the unit cell volume oft-ZrO2using Vegard's law. Using this information the compositional fluctuations over the sample were determined by considering two possible distributions of lanthanide ion content in the powders: a Gaussian and a Log-normal one. It was found that the Gaussian distribution better fits the experimental data. It was eventually demonstrated that these results are physically meaningful.
Identifying the multiplicity of crystallographically equivalent variants generated by iterative phase transformations in Ti
Authors: Grammatikopoulos Panagiotis , Pond Robert Charles
Published: January 2016

This work describes phase transformations in Ti from a purely crystallographic perspective. Iterative heating and cooling above and below 1155 K induce phase transitions between a low-temperature h.c.p. (hexagonal close packed) ({6 \over m}mm) and a high-temperature b.c.c. (body centred cubic) (m\bar 3m) structure. The crystallography of the two phases has been found to be related by the Burgers Orientation Relationship (Burgers OR). The transitions are accompanied by changes in texture, as an ever-increasing number of crystallographically equivalent variants occur with every cycle. Identifying their multiplicity is important to relate the textures before and after the transformation, in order to predict the resultant one and refine its microstructure. The four-dimensional Frank space was utilized to describe both h.c.p. and b.c.c. structures within the same orthogonal framework, and thus allow for their easy numerical manipulation through matrix algebra. Crystallographic group decomposition showed that the common symmetry maintained in both groups was that of group 2/m; therefore, the symmetry operations that generated the variants were of groups 3mand 23 for cubic and hexagonal generations, respectively. The number of all potential variants was determined for the first three variant generations, and degeneracy was indeed detected, reducing the number of variants from 72 to 57 and from 432 to 180 for the second and third generations, respectively. Degeneracy was attributed on some special alignments of symmetry operators, as a result of the Burgers OR connecting the relative orientation of the two structures.
HexagonalRMnO3: a model system for two-dimensional triangular lattice antiferromagnets
Authors: Sim Hasung , Oh Joosung , Jeong Jaehong , Le Manh Duc , Park Je-Geun
Published: January 2016

The hexagonalRMnO3(h-RMnO3) are multiferroic materials, which exhibit the coexistence of a magnetic order and ferroelectricity. Their distinction is in their geometry that both results in an unusual mechanism to break inversion symmetry and also produces a two-dimensional triangular lattice of Mn spins, which is subject to geometrical magnetic frustration due to the antiferromagnetic interactions between nearest-neighbor Mn ions. This unique combination makes theh-RMnO3a model system to test ideas of spin-lattice coupling, particularly when both the improper ferroelectricity and the Mn trimerization that appears to determine the symmetry of the magnetic structure arise from the same structure distortion. In this review we demonstrate how the use of both neutron and X-ray diffraction and inelastic neutron scattering techniques have been essential to paint this comprehensive and coherent picture ofh-RMnO3.
Heterocyclic Aromatic Amines in Cooked Meat Products: Causes, Formation, Occurrence, and Risk Assessment
Authors: Gibis Monika
Published: January 2016

Meat products are sources of protein with high biological value and an essential source of other nutrients, such as vitamins and minerals. Heating processes cause food to become more appetizing with changes in texture, appearance, flavor, and chemical properties by the altering of protein structure and other ingredients. During heat treatment, heterocyclic aromatic amines (HAAs), potent mutagens/carcinogens, are formed due to the Maillard reaction. The HAAs are classified in at least 2 groups: thermic HAAs (100 to 300 °C) and pyrolytic HAAs (>300 °C). This review focuses on the parameters and precursors which affect the formation of HAAs: preparation, such as the marinating of meat, and cooking methods, including temperature, duration, and heat transfer, as well as levels of precursors. Additionally, factors are described subject to pH, and the type of meat and ingredients, such as added antioxidants, types of carbohydrates and amino acids, ions, fat, and other substances inhibiting or enhancing the formation of HAAs. An overview of the different analytical methods available is shown to determine the HAAs, including their preparation to clean up the sample prior to extraction. Epidemiological results and human daily intake of HAAs obtained from questionnaires show a relationship between the preference for very well‐done meat products with increased HAA levels and an enhanced risk of the incidence of cancer, besides other carcinogens in the diet. The metabolic pathway of HAAs is governed by the activity of several enzymes leading to the formation of DNA adducts or HAA excretion and genetic sensitivity of individuals to the impact of HAAs on human cancer risk.
Mycotoxins in Bovine Milk and Dairy Products: A Review
Authors: Becker‐Algeri Tania Aparecida , Castagnaro Denise , de Bortoli Kennidy , de Souza Camila , Drunkler Deisy Alessandra , Badiale‐Furlong Eliana
Published: January 2016

This paper presents a literature review of the occurrence of several mycotoxins in bovine milk and dairy products, because it is the main type of milk produced and marketed worldwide. Mycotoxins are produced by different genera of filamentous fungi and present serious health hazards such as carcinogenicity and mutagenicity. Under favorable growth conditions, toxigenic fungi produce mycotoxins which contaminate the lactating cow's feedstuff. During metabolism, these mycotoxins undergo biotransformation and are secreted in milk. Data show that there is a seasonal trend in the levels of mycotoxins in milk, with these being higher in the cold months probably due to the prolonged storage required for the cattle feeds providing favorable conditions for fungal growth. Good agricultural and storage practices are therefore of fundamental importance in the control of toxigenic species and mycotoxins. Although aflatoxins (especially aflatoxin M1) are the mycotoxins of greater incidence in milk and dairy products, this review shows that other mycotoxins, such as fumonisin, ochratoxin A, trichothecenes, zearalenone, T‐2 toxin, and deoxynivalenol, can also be found in these products. Given that milk is widely consumed and is a source of nutrients, especially in childhood, a thorough investigation of the occurrence of mycotoxins as well the adoption of measures to minimize their contamination of milk is essential.
Extension of the Vane Pump‐Grinder Technology to Manufacture Finely Dispersed Meat Batters
Authors: Irmscher Stefan B. , Gibis Monika , Herrmann Kurt , Oechsle Anja Maria , Kohlus Reinhard , Weiss Jochen
Published: January 2016

A vane pump‐grinder system was extended to enable the manufacture of finely dispersed emulsion‐type sausages by constructing and attaching a high‐shear homogenizer at the outlet. We hypothesized that the dispersing capabilities of the extended system may be improved to the point of facilitating meat‐fat emulsification due to an overall increased volumetric energy input EV. Coarsely ground raw material mixtures were processed to yield meat batters at varying volume flow rates (10 to 60 L/min) and rotational rotor speeds of the homogenizer nrotor (1000 to 3400 rpm). The normalized torques acting on pump, grinder, and homogenizer motors were recorded and unit power consumptions were calculated. The structure of the manufactured meat batters and sausages were analyzed via image analysis. Key physicochemical properties of unheated and heated batters, that is, texture, water‐binding, color, and solubilized protein were determined. The mean diameter d10 of the visible lean meat particles varied between 352 and 406 μm whereas the mean volume‐surface diameter d32 varied between 603 and 796 μm. The lightness L* ranged from 66.2 to 70.7 and correlated with the volumetric energy input and product structure. By contrast, varying process parameters did not impact color values a* (approximately 11) and b* (approximately 8). Interestingly, water‐binding and protein solubilization were not affected. An exponential process‐structure relationship was identified allowing manufacturers to predict product properties as a function of applied process parameters. Raw material mixtures can be continuously comminuted, emulsified, and subsequently filled into casings using an extended vane pump‐grinder.
Effects of Long‐Chain and Medium‐Chain Fatty Acids on Apoptosis and Oxidative Stress in Human Liver Cells with Steatosis
Authors: Wang Baogui , Li Lumin , Fu Jing , Yu Ping , Gong Deming , Zeng Cheng , Zeng Zheling
Published: January 2016

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity‐related metabolic complications, which caused by excess energy intake and physical inactivity apart from genetic defects. The mechanisms that promote disease progression from NAFLD to further liver injury are still unclear. We hypothesize that the progression involved “2nd hit” is strongly influenced by the type of fatty acids in diets. Flow cytometric analysis showed that medium‐chain fatty acid (MCFA) markedly decreased the percentage of late apoptotic and necrotic cells compared with long‐chain fatty acid (LCFA), and MCFA inhibited the activities of caspase‐3 and ‐9 in human liver cells with steatosis. Western blot analysis found that the levels of inflammatory markers (interleukin [IL]‐6, IL‐1‐β, and tumor necrosis factor‐α) were substantially reduced by MCFA compared with LCFA. Proteomic analysis further showed that LCFA inhibited the expression of antioxidant enzymes, and increased the expression of proteins associated with oxidative stress. It was found that LCFA (palmitate), not MCFA induced apoptosis, oxidative stress and chronic inflammatory responses in the hepatic cells with steatosis. In conclusion, reasonable selection of dietary fats has potential to translate therapeutically by ameliorating disease progression in patients with NAFLD.
Effect of Storage on the Physico‐Chemical and Antioxidant Properties of Strawberry and Kiwi Leathers
Authors: Concha‐Meyer Anibal A. , D'Ignoti Valeria , Saez Barbara , Diaz Ricardo I. , Torres Carolina A.
Published: January 2016

Strawberry and kiwi leathers were used to develop a new healthy and preservative‐free fruit snack for new markets. Fruit puree was dehydrated at 60 °C for 20 h and subjected to accelerated storage. Soluble solids, titratable acidity, pH, water activity (aw), total phenolic (TP), antioxidant activity (AOA) and capacity (ORAC), and color change (browning index) were measured in leathers, cooked, and fresh purees. An untrained panel was used to evaluate consumer acceptability. Soluble solids of fresh purees were 11.24 to 13.04 °Brix, whereas pH was 3.46 to 3.39. Leathers presented an aw of 0.59 to 0.67, and a moisture content of 21 kg water/100 kg. BI decreased in both leathers over accelerated storage period. TP and AOA were higher (P ≤ 0.05) in strawberry formulations. ORAC decreased 57% in strawberry and 65% in kiwi leathers when compared to fruit puree. TP and AOA increased in strawberries during storage. Strawberry and Kiwi leathers may be a feasible new, natural, high antioxidant, and healthy snack for the Chilean and other world markets, such as Europe, particularly the strawberry leather, which was preferred by untrained panelists.
Engineering Digestion: Multiscale Processes of Food Digestion
Authors: Bornhorst Gail M. , Gouseti Ourania , Wickham Martin S.J. , Bakalis Serafim
Published: January 2016

Food digestion is a complex, multiscale process that has recently become of interest to the food industry due to the developing links between food and health or disease. Food digestion can be studied by using either in vitro or in vivo models, each having certain advantages or disadvantages. The recent interest in food digestion has resulted in a large number of studies in this area, yet few have provided an in‐depth, quantitative description of digestion processes. To provide a framework to develop these quantitative comparisons, a summary is given here between digestion processes and parallel unit operations in the food and chemical industry. Characterization parameters and phenomena are suggested for each step of digestion. In addition to the quantitative characterization of digestion processes, the multiscale aspect of digestion must also be considered. In both food systems and the gastrointestinal tract, multiple length scales are involved in food breakdown, mixing, absorption. These different length scales influence digestion processes independently as well as through interrelated mechanisms. To facilitate optimized development of functional food products, a multiscale, engineering approach may be taken to describe food digestion processes. A framework for this approach is described in this review, as well as examples that demonstrate the importance of process characterization as well as the multiple, interrelated length scales in the digestion process.
Coalho Cheese Made with Protease from Thermomucor indicae‐seudaticae N31: Technological Potential of the New Coagulant for the Production of High‐Cooked Cheese
Authors: Merheb‐Dini Carolina , Chaves Karina S. , Gomes Eleni , da Silva Roberto , Gigante Mirna L.
Published: January 2016

The aim of this study was to explore the use of a new coagulant from Thermomucor indicae‐seudaticae N31 for the manufacture of a high‐cooked starter‐free cheese variety, by evaluating its physicochemical and functional characteristics in comparison to cheeses made with a traditional commercial coagulant. Coalho cheese was successfully produced with the new protease as it exhibited comparable characteristics to the one produced using the commercial enzyme: pH behavior during manufacture; cheese composition; protein and fat recovery; and cheese yield. In addition, during storage, melting was low and not affected by storage time; the increase of TCA 12% soluble nitrogen (% of total nitrogen) was lower than half of that of pH 4.6 soluble nitrogen (% of total nitrogen); concentration of β‐CN significantly decreased, whereas αs1‐CN concentration was not affected by storage time.
Interpreting the National Hospital Ambulatory Medical Care Survey: United States Emergency Department Opioid Prescribing, 2006–2010
Authors: Kea Bory , Fu Rochelle , Lowe Robert A. , Sun Benjamin C.
Published: January 2016

Objectives

Prescription opioid overdoses are a leading cause of death in the United States. Emergency departments (EDs) are potentially high‐risk environments for doctor shopping and diversion. The hypothesis was that opioid prescribing rates from the ED have increased over time.

Methods

The authors analyzed data on ED discharges from the 2006 through 2010 NHAMCS, a probability sample of all U.S. EDs. The outcome was documentation of an opioid prescription on discharge. The primary independent predictor was time. Covariates included severity of pain, a pain‐related discharge diagnosis, age, sex, race, payer, hospital ownership, and geographic location of hospital. Up to three discharge diagnoses were available in NHAMCS to identify “pain‐related” (e.g., back pain, fracture, dental/jaw pain, nephrolithiasis) ED visits. Multivariate logistic regression was performed to assess the independent associations between opioid prescribing and predictors. All analyses incorporated NHAMCS survey weights, and all results are presented as national estimates.

Results

Opioids were prescribed for 18.7% (95% confidence interval = 17.7% to 19.7%) of all ED discharges, representing 18.8 million prescriptions per year. There were no significant temporal trends in opioid prescribing overall (adjusted p = 0.93). Pain‐related discharge diagnoses that received the top three highest proportion of opioids prescriptions included nephrolithiasis (62.1%), neck pain (51.6%), and dental/jaw pain (49.7%). A pain‐related discharge diagnosis, non‐Hispanic white race, older age, male sex, uninsured status, and Western region were positively associated with opioid prescribing (p < 0.05).

Conclusions

No temporal trend toward increased prescribing from 2006 to 2012 was found. These results suggest that problems with opioid overprescribing are multifactorial and not solely rooted in the ED.
Physician Preparation for the American Board of Emergency Medicine ConCert Examination
Authors: Marco Catherine A. , Wahl Robert P. , Counselman Francis L. , Heller Barry N. , Kowalenko Terry , Harvey Anne L. , Joldersma Kevin B. , Reisdorff Earl J.
Published: January 2016

Objectives

To maintain certification by the American Board of Emergency Medicine (ABEM), physicians are required to pass the Continuous Certification (ConCert) examination at least every 10 years. On the 2014 ConCert postexamination survey, ABEM sought to understand the manner in which ABEM diplomates prepared for the test and to identify associations between test preparation approaches and performance on the ConCert examination.

Methods

This was a cross‐sectional survey study. The survey was administered at the end of the 2014 ConCert examination. Analyses included chi‐square and linear regression to determine the association of preparation methods with performance.

Results

Of the 2,431 on‐time test‐takers, 2,338 (96.2%) were included. The most commonly used study approach was the review of written materials designed for test preparation (1,585; 67.8%), followed by an online training course (1,006; 43.0%). There were 758 (32.4%) physicians who took a single onsite board review course, while 41 (1.8%) took two or more onsite courses. Most physicians (1,611; 68.9%) spent over 35 hours preparing for the ConCert examination. The study method that was most associated with favorable test scores was the review of written materials designed for test preparation (p < 0.001). Attending an onsite preparation course was associated with poorer performance (p < 0.001). There was a significant association between no additional preparation and failing the examination (chi‐square with Yates correction; p = 0.001).

Conclusions

A substantial majority (97.8%) of physicians taking the 2014 ABEM ConCert examination prepared for it. The majority of physicians used written materials specifically designed for test preparation. Reviewing written materials designed for test preparation was associated with the highest performance.
A Comparison of the Effect of Interposed Abdominal Compression Cardiopulmonary Resuscitation and Standard Cardiopulmonary Resuscitation Methods on End‐tidal CO2 and the Return of Spontaneous Circulation Following Cardiac Arrest: A Clinical Trial
Authors: Movahedi Ali , Mirhafez Seyed Reza , Behnam‐Voshani Hamidreza , Reihani Hamidreza , Kavosi Ali , Ferns Gordon A. , Malekzadeh Javad
Published: January 2016

Objectives

Sudden cardiac arrest is a major cause of death in the adult population of developed countries, with only 10%–15% of cardiopulmonary resuscitations (CPRs) being successful. We aimed to compare the effects of interposed abdominal compression CPR (IAC‐CPR) with standard CPR (STD‐CPR) methods on end‐tidal CO2 (ETCO2) and the return of spontaneous circulation (ROSC) following cardiac arrest in a hospital setting.

Methods

After cardiac arrest was confirmed in a patient at Mashhad Ghaem Hospital, 80 cases were randomly assigned to one of the two methods of resuscitation, either IAC‐CPR or STD‐CPR, respectively. The inclusion criteria for the study were nontraumatic cardiac arrest, in patients between the age of 18 and 85 years, and the presence of endotracheal tube. Exclusion criteria were abdominal surgery in the past 2 weeks, active gastrointestinal bleeding, pulmonary embolism, and suspected pregnancy.

Results

There was a significant difference between the two groups in ETCO2 (p < 0.003), but there was no significant difference as far as the ROSC (p > 0.50).

Conclusion

The increase in the ETCO2 during IAC‐CPR is an indicator of the increase in cardiac output following the use of this method of CPR.
Who thinks what about e‐cigarette regulation? A content analysis of UK newspapers
Authors: Patterson Chris , Hilton Shona , Weishaar Heide
Published: January 2016

Aims

To establish how frequently different types of stakeholders were cited in the UK media debate about e‐cigarette regulation, their stances towards different forms of e‐cigarette regulation, and what rationales they employed in justifying those stances.

Methods

Quantitative and qualitative content analyses of 104 articles about e‐cigarette regulation published in eight UK and three Scottish national newspapers between 1 January 2013 and 31 December 2014.

Results

Reporting on e‐cigarette regulation grew significantly (P < 0.001) throughout the sample period. Governments and regulatory bodies were the most frequently cited stakeholders and uniformly supported regulation, while other stakeholders did not always support regulation. Arguments for e‐cigarette regulation greatly outnumbered arguments against regulation. Regulating purchasing age, restricting marketing and regulating e‐cigarettes as medicine were broadly supported, while stakeholders disagreed about prohibiting e‐cigarette use in enclosed public spaces. In rationalizing their stances, supporters of regulation cited child protection and concerns about the safety of e‐cigarette products, while opponents highlighted the potential of e‐cigarettes in tobacco cessation and questioned the evidence base associating e‐cigarette use with health harms.

Conclusions

In the UK between 2013 and 2014, governments and tobacco control advocates frequently commented on e‐cigarettes in UK‐wide and Scottish national newspapers. Almost all commentators supported e‐cigarette regulation, but there was disagreement about whether e‐cigarette use should be allowed in enclosed public spaces. This appeared to be linked to whether commentators emphasized the harms of vapour and concerns about renormalizing smoking or emphasized the role of e‐cigarettes as a smoking cessation aid.
Metronomic therapy can increase quality of life during paediatric palliative cancer care, but careful patient selection is essential
Authors: Porkholm Mikaela , Toiviainen‐Salo Sanna , Seuri Raija , Lönnqvist Tuula , Vepsäläinen Kaisa , Saarinen‐Pihkala Ulla M. , Pentikäinen Virve , Kivivuori Sanna‐Maria
Published: January 2016

Aim

Children with refractory or high‐risk malignancies frequently suffer from poor quality of life during palliative care. This study explored the effect of metronomic drug administration on survival and quality of life in paediatric patients with various refractory or high‐risk tumours.

Methods

We treated 17 patients with a maintenance therapy that consisted of metronomic thalidomide, etoposide and celecoxib. The endpoints of the study were overall and progression‐free survival, changes in the Karnofsky–Lansky scores from baseline to the end of the study therapy and radiological responses.

Results

The median overall survival after the start of the study therapy was 6.2 months (range 2.0–57.7), and the six‐, 12‐ and 24‐month survival rates were 59%, 18% and 18%, respectively. The median progression‐free survival was 3.2 months (range 0.3–17.8). The Karnofsky–Lansky scores increased significantly during the study therapy (p = 0.02), with 35% of the patients having a transient improvement in their clinical status. Radiologically, one partial response and two disease stabilisations were encountered. Grade III‐V adverse events occurred in 76% of the patients.

Conclusion

Metronomic therapy may increase the quality of life during palliative care for childhood cancer, but requires careful patient selection to minimise the risk of serious adverse events.
Resuscitators who compared four simulated infant cardiopulmonary resuscitation methods favoured the three‐to‐one compression‐to‐ventilation ratio
Authors: Boldingh Anne Marthe , Solevåg Anne Lee , Aasen Elisabeth , Nakstad Britt
Published: January 2016

Aim

Suboptimal cardiopulmonary resuscitation (CPR) is associated with a poor outcome, and international guidelines state that resuscitators should optimise compression and ventilation techniques with as few interruptions as possible. We investigated compression and ventilation quality during simulated CPR with four compression‐to‐ventilation (C:V) methods.

Methods

In this crossover manikin study, 42 pairs of doctors, nurses, midwives and sixth‐year medical students from two Norwegian hospitals provided two‐minute resuscitation using the 3:1, 9:3 and 15:2 C:V methods and continuous chest compressions at 120 per minute with asynchronous ventilations (CCaV‐120). We measured chest compression, ventilation mechanics and the resuscitators' preferences.

Results

C:V methods 3:1 and 9:3 provided comparable chest compressions and ventilation mechanics, whereas 15:2 produced fewer ventilations and lower minute volumes. The CCaV‐120 method was significantly less effective than the 3:1 C:V ratio method: the chest compression depth was 1.9 mm lower, there were 25 fewer chest compressions and 21 fewer ventilations per minute, and the minute volume was 69 mL lower. The 3:1 C:V method also provided better coordination between resuscitators.

Conclusion

Our comparison of four simulated infant cardiopulmonary resuscitation methods favoured the 3:1 C:V method, and the multidisciplinary group of participants felt it offered the best level of coordination between resuscitators.
Identification of neonatal haemolysis: an approach to predischarge management of neonatal hyperbilirubinemia
Authors: Bhutani Vinod K. , Srinivas Shanmukha , Castillo Cuadrado Martin E. , Aby Janelle L. , Wong Ronald J. , Stevenson David K.
Published: January 2016

Aim

Relative contributions of increased production [by end‐tidal carbon monoxide concentrations (ETCOc)] and decreased elimination of bilirubin to predischarge hour‐specific total bilirubin (TB) levels were assessed in healthy late‐preterm and term newborns. Secondly, we report predischarge ETCOc ranges to guide clinical management of hyperbilirubinemia.

Methods

TB and ETCOc (≤3 timepoints) determinations of newborns aged between six hours and <6 days (n = 79) were stratified by postnatal age epochs. Hyperbilirubinemia risk was assessed by plotting TB values as a function of ETCOc.

Results

Stratifications of ETCOc (in ppm, mean, median and interquartile ranges) by postnatal age epochs (0–24, 24–48 and 48–72) were as follows: 2.0, 1.9, 1.8–2.2 (n = 11); 1.6, 1.5, 1.1–2.0 (n = 58); and 2.0, 1.8, 1.6–2.3 (n = 9), respectively. Infants with ETCOc ≥ 2.5 were at high risk, between 1.5 and 2.5 at moderate risk and ≤1.5 were at low risk. Risk due to haemolysis alone was not independent (p < 0.01). For infants with TB >75th percentile (n = 31), 23% had ETCO ≤1.5, and 77% had ETCOc > 1.5 (p < 0.00003).

Conclusion

Near‐simultaneous ETCOc and TB measurements in infants with TB >75th percentile accurately identify haemolytic hyperbilirubinemia.
Estimating Treatment Effect in a Proportional Hazards Model in Randomized Clinical Trials with All-or-Nothing Compliance
Authors: Li Shuli , Gray Robert J.
Published: January 2016

We consider methods for estimating the treatment effect and/or the covariate by treatment interaction effect in a randomized clinical trial under noncompliance with time-to-event outcome. As in Cuzick et al. (2007), assuming that the patient population consists of three (possibly latent) subgroups based on treatment preference: the ambivalent group, the insisters, and the refusers, we estimate the effects among the ambivalent group. The parameters have causal interpretations under standard assumptions. The article contains two main contributions. First, we propose a weighted per-protocol (Wtd PP) estimator through incorporating time-varying weights in a proportional hazards model. In the second part of the article, under the model considered in Cuzick et al. (2007), we propose an EM algorithm to maximize a full likelihood (FL) as well as the pseudo likelihood (PL) considered in Cuzick et al. (2007). The E step of the algorithm involves computing the conditional expectation of a linear function of the latent membership, and the main advantage of the EM algorithm is that the risk parameters can be updated by fitting a weighted Cox model using standard software and the baseline hazard can be updated using closed-form solutions. Simulations show that the EM algorithm is computationally much more efficient than directly maximizing the observed likelihood. The main advantage of the Wtd PP approach is that it is more robust to model misspecifications among the insisters and refusers since the outcome model does not impose distributional assumptions among these two groups.
Molecular and functional characterization of Kv7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats
Authors: Jepps T A , Olesen S P , Greenwood I A , Dalsgaard T
Published: January 2016

Background and Purpose

KCNQ‐encoded voltage‐dependent potassium channels (Kv7) are involved in the regulation of vascular tone. In this study we evaluated the influence of Kv7 channel activation on smooth muscle relaxation in rat penile arteries and corpus cavernosum from normal and spontaneously hypertensive, heart failure‐prone (SHHF) rats – a rat model of human metabolic syndrome.

Experimental Approach

Quantitative PCR and immunohistochemistry were used to determine the expression of KCNQ isoforms in penile tissue. Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from normal and SHHF rats.

Key Results

Transcripts for KCNQ3, KCNQ4 and KCNQ5 were detected in penile arteries and corpus cavernosum. KCNQ1 was only found in corpus cavernosum. Immunofluorescence signals to Kv7.4 and Kv7.5 were found in penile arteries, penile veins and corpus cavernosum. The Kv7.2–7.5 activators, ML213 and BMS204352, relaxed pre‐contracted penile arteries and corpus cavernosum independently of nitric oxide synthase or endothelium‐derived hyperpolarization. Relaxations to sildenafil, a PDE5 inhibitor, and sodium nitroprusside (SNP), an nitric oxide donor, were reduced by blocking Kv7 channels with linopirdine in penile arteries and corpus cavernosum. In SHHF rat penile arteries and corpus cavernosum, relaxations to ML213 and BMS204352 were attenuated, and the blocking effect of linopirdine on sildenafil‐induced and SNP‐induced relaxations reduced. KCNQ3, KCNQ4 and KCNQ5 were down‐regulated, and KCNQ1 was up‐regulated in corpus cavernosum from SHHF rats. KCNQ1–5 transcripts remained unchanged in penile arteries from SHHF rats.

Conclusions and Implications

These data suggest that Kv7 channels play a role in erectile function and contribute to the pathophysiology of erectile dysfunction, an early indicator of cardiovascular disease.
NPYFa, A Chimeric Peptide of Met‐Enkephalin, and NPFF Induces Tolerance‐Free Analgesia
Authors: Mudgal Annu , Kumar Krishan , Mollereau Catherine , Pasha Santosh
Published: January 2016

Methionine‐enkephalin‐Arg‐Phe is an endogenous amphiactive analgesic peptide. Neuropeptide FF, on the other hand, is reported for its role in opioid modulation and tolerance development. Based on these reports, in the present study we designed a chimeric peptide NPYFa (YGGFMKKKPQRFamide), having the Met‐enkephalin (opioid) and PQRFamide sequence of neuropeptide FF, which can then target both the opioid and neuropeptide FF receptors. We hypothesized that the chimeric peptide so designed would have both analgesic properties and further aid in understanding of the role of neuropeptide FF in the development of opiate tolerance. Our studies indicated that NPYFa induced an early onset, potent, dose‐dependent and prolonged antinociception. Additionally, antagonists (MOR, KOR, and DOR) pretreatment studies determined a KOR‐mediated antinociception activity of the ligand. Further, in vitro binding studies using the Eu‐GTP‐γS binding assay on cell lines expressing opioid and NPFF receptors showed binding to both the opioid and neuropeptide FF receptors suggesting a multiple receptor binding character of NPYFa. Moreover, chronic (6 days) treatment with NPYFa exhibited an absence of tolerance development subsequent to its analgesia. The current study proposes NPYFa as a potent, long‐acting antinociceptor lacking tolerance development as well as a probe to study opioid analgesia and the associated complex mechanisms of tolerance development.
Cognitive Control as a Moderator of Temperamental Motivations Toward Adolescent Risk‐Taking Behavior
Authors: Youssef George J. , Whittle Sarah , Allen Nicholas B. , Lubman Dan I. , Simmons Julian G. , Yücel Murat
Published: January 2016

Few studies have directly examined whether cognitive control can moderate the influence of temperamental positive and negative affective traits on adolescent risk‐taking behavior. Using a combined multimethod, latent variable approach to the assessment of adolescent risk‐taking behavior and cognitive control, this study examined whether cognitive control moderates the influence of temperamental surgency and frustration on risk‐taking behavior in a sample of 177 adolescents (Mage = 16.12 years, SD = 0.69). As predicted, there was a significant interaction between cognitive control and frustration, but not between cognitive control and surgency, in predicting risk‐taking behavior. These findings have important implications and suggest that the determinants of adolescent risk taking depend on the valence of the affective motivation for risk‐taking behavior.