bluuebunny/crossref_metadata_2025 huggingface dataset:
Sand consolidation via latex destabilization
Authors: Gun Wei Jin , Routh Alexander F. , Aytkhozhina Dana , Aston Mark
Published: February 2017

This article investigates the use of a commercial latex dispersion for the purpose of sand consolidation in oil wells. The aim is to consolidate sand without compromising permeability and to prevent sanding during water breakthrough. This is achieved by injecting latex dispersions into a sand‐pack and relying on potassium chloride flushes, or irreducible saline water in the reservoir, to destabilize the latex onto the sand surface. This forms a latex network connecting and holding the sand grains together. The strength of the consolidation in the laboratory is determined by flowing water and oil at various flow rates and investigating the amount of sand produced. The effect of different parameters, such as the amount of latex injected, the latex salinity, and salinity of the irreducible water are discussed. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2610–2617, 2017
Preparation and solution performance for the amphiphilic polymers with different hydrophobic groups
Authors: Zhu Zhou , Kang Wanli , Sarsenbekuly Bauyrzhan , Yang Hongbin , Dai Caili , Yang Runmei , Fan Haiming
Published: February 2017

An amphiphilic polymer with twin‐tailed hydrophobic groups was prepared by micellar polymerization of acrylamide as hydrophilic monomers, 2‐acryloylamino‐2‐methyl‐1‐propanesulfonic acid as functional monomers and N,N‐dodecyl acrylamide as hydrophobic monomers. Using the same method, containing single‐tailed hydrophobic group of the amphiphilic polymer and not containing the hydrophobic group of ordinary polymer were prepared. The molecular structure of the product was characterized by infrared spectrum and 1H nuclear magnetism resonance spectrum. By inclusion complexation of β‐cyclodextrin (β‐CD), the hydrophobic association on the apparent viscosity contribution rate was studied. Relationship between hydrophobic group structure and its performance was investigated by the rotational viscometer, scanning electron microscopy (SEM), fluorescence spectroscopy, and rheometer. The results showed that amphiphilic polymers containing twin‐tailed hydrophobic groups had a lower critical aggregation concentration (CAC). When the amphiphilic polymer concentration was higher than CAC, hydrophobic association was stronger, which led to a higher apparent viscosity contribution rate. At the same polymer solution concentration, amphiphilic polymer containing twin‐tailed hydrophobic group had better performance on temperature resistance, salt tolerance, and mechanical shear resistance compared with the other two polymers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44744.
Aneurysm sealing
Authors: Hinchliffe R J
Published: February 2017

Compulsory registration needed
Prenatal diagnosis of X‐linked myopathy associated with a VMA21 gene mutation afforded through a novel targeted exome sequencing strategy applied in fetuses with abnormal ultrasound findings
Authors: Konialis Christopher , Assimakopoulos Efstratios , Hagnefelt Birgitta , Karapanou Sophia , Sotiriadis Alexandros , Pangalos Constantinos
Published: February 2017

Key Clinical Message

Fetal malformations detected through routine prenatal ultrasound examination comprise a heterogeneous group potentially associated with genetic disorders where the underlying cause is difficult to establish. We present the prenatal diagnosis of a rare X‐linked myopathy involving a new VMA21 gene mutation, detected through a novel prenatal exome sequencing‐based approach.
Application of Partial Least Squares‐Kernel Calibration in Competitive Adsorption Studies Using an Effective Chemically Activated Biochar
Authors: Issa Ayman A. , Al‐Degs Yahya S. , El‐Sheikh Amjad H. , Al‐Reyahi Anas Y. , Bakain Ramia Z.Al , Abdelghani Jafar I. , Newman Alan P.
Published: February 2017

In this work, chemically activated pine wood was used to prepare biochar, which was used to study the competitive adsorption behavior of four colorants (allura red (AR), brilliant black (BB), tartrazine (TT), and sunset yellow (SY)). Dye concentrations in mixed solutions were simultaneously estimated by using partial least squares Kernel calibration. The analytical recovery of food dyes was 96.7–103.4% and prediction error was 1.4–9.4%. Adsorption isotherms of dyes (at pH 2 and 25°C) from multi‐solute solutions were measured and the maximum adsorption capacities (according to the Jovanovich's model) were 68.4, 40.0, 29.6, and 23.4 mg/g for SY, AR, TT, and BB, respectively. The biochar had a combined retention capacity of 186.9 mg/g for dyes. The effects of dosage of adsorbent, pH and number of competing solutes on %Removal‐retention capacity were studied. The extent of competition between dyes toward the surface was assessed from the magnitudes of competition factors. The competition factors were 0.69, 0.70, 0.75, and 0.76 for AR, TT, BB, and SY, respectively. During adsorption of mixtures from solution, SY manifested stable performance while allura red negatively competed with the rest of the dyes. Partial least squares Kernel calibration was usefully applied for studying competitive adsorption behavior of four food‐dyes with minimum experimental setup.
Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity
Authors: Hannibal Jens , Christiansen Anders Tolstrup , Heegaard Steffen , Fahrenkrug Jan , Kiilgaard Jens Folke
Published: February 2017

Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N‐ and C‐terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (‐ir) RGCs, we applied the criteria used in mouse on human melanopsin‐ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin‐ir RGCs, which were named “gigantic M1 (GM1)” and “gigantic displaced M1 (GDM1).” Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin‐ir (0.63–0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin‐ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin‐ir RGCs, which most likely are involved in different functions.
Stabilization Effect of Amino Acid Side Chains in Peptide Assemblies on Graphite Studied by Scanning Tunneling Microscopy
Authors: Guo Yuanyuan , Hou Jingfei , Zhang Xuemei , Yang Yanlian , Wang Chen
Published: February 2017

An analysis is presented of the effects of amino acid side chains on peptide assemblies in ambient conditions on a graphite surface. The molecularly resolved assemblies of binary peptides are examined with scanning tunneling microscopy. A comparative analysis of the assembly structures reveals that the lamellae width has an appreciable dependence on the peptide sequence, which could be considered as a manifestation of a stabilizing effect of side‐chain moieties of amino acids with high (phenylalanine) and low (alanine, asparagine, histidine and aspartic acid) propensities for aggregation. These amino acids are representative for the chemical structures involving the side chains of charged (histidine and aspartic acid), aromatic (phenylalanine), hydrophobic (alanine), and hydrophilic (asparagine) amino acids. These results might provide useful insight for understanding the effects of sequence on the assembly of surface‐bound peptides.
Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy
Authors: Török ME , Aljayyoussi G , Waterhouse D , Chau TTH , Mai NTH , Phu NH , Hien TT , Hope W , Farrar JJ , Ward SA
Published: February 2017

A placebo‐controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti‐HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV –ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure.
A Call for a Consortium for Optimal Management of Drug–Drug Interactions in Patient Care
Authors: Burger DM , Smolders EJ , Schapiro J , Drenth JPH , Back DJ
Published: February 2017

During clinical development of medicines, manufacturers are obliged to assess the risk of drug–drug interactions (DDIs) with their new drug. There is no doubt that product labels of drugs that are nowadays introduced to the market contain much more information on DDIs than in the past. Indeed, the drug label is often the first source for DDIs available to physicians and pharmacists. But how informative are the data presented in the drug labels?
Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta‐analysis
Authors: Saffian SM , Duffull SB , Wright DFB
Published: February 2017

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta‐analysis of warfarin dosing algorithms to determine if there exists a systematic under‐ or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over‐ and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta‐analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta‐analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3–94.1, I2 = 24%).
Evaluating flow cytometer performance with weighted quadratic least squares analysis of LED and multi‐level bead data
Authors: Parks David R. , El Khettabi Faysal , Chase Eric , Hoffman Robert A. , Perfetto Stephen P. , Spidlen Josef , Wood James C.S. , Moore Wayne A. , Brinkman Ryan R.
Published: February 2017

We developed a fully automated procedure for analyzing data from LED pulses and multilevel bead sets to evaluate backgrounds and photoelectron scales of cytometer fluorescence channels. The method improves on previous formulations by fitting a full quadratic model with appropriate weighting and by providing standard errors and peak residuals as well as the fitted parameters themselves. Here we describe the details of the methods and procedures involved and present a set of illustrations and test cases that demonstrate the consistency and reliability of the results. The automated analysis and fitting procedure is generally quite successful in providing good estimates of the Spe (statistical photoelectron) scales and backgrounds for all the fluorescence channels on instruments with good linearity. The precision of the results obtained from LED data is almost always better than that from multilevel bead data, but the bead procedure is easy to carry out and provides results good enough for most purposes. Including standard errors on the fitted parameters is important for understanding the uncertainty in the values of interest. The weighted residuals give information about how well the data fits the model, and particularly high residuals indicate bad data points. Known photoelectron scales and measurement channel backgrounds make it possible to estimate the precision of measurements at different signal levels and the effects of compensated spectral overlap on measurement quality. Combining this information with measurements of standard samples carrying dyes of biological interest, we can make accurate comparisons of dye sensitivity among different instruments. Our method is freely available through the R/Bioconductor package flowQB. © 2017 International Society for Advancement of Cytometry
Imaging Mass Cytometry
Authors: Chang Qing , Ornatsky Olga I. , Siddiqui Iram , Loboda Alexander , Baranov Vladimir I. , Hedley David W.
Published: February 2017

Imaging Mass Cytometry (IMC) is an expansion of mass cytometry, but rather than analyzing single cells in suspension, it uses laser ablation to generate plumes of particles that are carried to the mass cytometer by a stream of inert gas. Images reconstructed from tissue sections scanned by IMC have a resolution comparable to light microscopy, with the high content of mass cytometry enabled through the use of isotopically labeled probes and ICP‐MS detection. Importantly, IMC can be performed on paraffin‐embedded tissue sections, so can be applied to the retrospective analysis of patient cohorts whose outcome is known, and eventually to personalized medicine. Since the original description in 2014, IMC has evolved rapidly into a commercial instrument of unprecedented power for the analysis of histological sections. In this Review, we discuss the underlying principles of this new technology, and outline emerging applications of IMC in the analysis of normal and pathological tissues. © 2017 International Society for Advancement of Cytometry
Cytological features of atypical polypoid adenomyoma of the endometrium: A case report with literature review
Authors: Ebisu Yusuke , Arimoto Tomoko , Ishida Mitsuaki , Miyasaka Chika , Uemura Yoshiko , Okada Hidetaka , Tsuta Koji
Published: February 2017

Atypical polypoid adenomyoma (APA) is a rare mixed epithelial and mesenchymal tumor characterized histopathologically by the presence of disorganized hyperplastic glands with cytological atypia embedded in intersecting fascicles of fibromuscular stromal cells. Herein, we report the first documented endometrial cytological case of APA. A 35‐year‐old Japanese female presented with irregular menstrual cycles and then was found to have polypoid lesions of the endometrium. Cytological examination of the endometrium and endometrial curettage were performed. The Papanicolaou smear revealed the presence of abundant clusters of crowded glandular cells in a clean background. These clusters exhibited irregular branching and dilatation, and these glandular cells had mild to moderately enlarged round to oval nuclei. Within the dilated glands, metaplastic squamous cells (squamous morules) were observed. The most striking feature was the presence of short fascicles of the spindle cells without atypia around the dilated atypical glandular cell clusters with squamous morules. Histopathological and immunohistochemical examinations revealed a diagnosis of APA. Our report demonstrates that the characteristic cytological feature suggestive of APA is the presence of short fascicles of the spindle cells without atypia surrounding dilated atypical glandular cell clusters with squamous morules in a clean background, and their appearance can allow cytologists/cytopathologists to consider APA in differential diagnosis in the endometrial cytological specimens. Diagn. Cytopathol. 2017;45:345–349. © 2016 Wiley Periodicals, Inc.
The significance of parakeratosis alone in cervicovaginal cytology of turkish women
Authors: Kir Gozde , Sarbay Billur Cosan , Seneldir Hatice
Published: February 2017

Background

We aimed to analyze the significance of parakeratosis on an otherwise negative Papanicalaou (Pap) smear, in the absence of any characteristic human papilloma virus (HPV) findings.

Methods

A total of 22,076 Papanicalaou smears that were diagnosed as negative for intraepithelial lesions or malignancy between 2013 and 2015 were included in this study. Samples were separated into two groups, according to the presence of parakeratosis. We investigated the association between parakeratosis in the cytology results and a high‐risk HPV status and high‐grade squamous intraepithelial lesion (HSIL) in the colposcopic biopsy specimens.

Results

A positive HPV result was more frequently identified in cases with parakeratosis than in cases without parakeratosis (P < 0.001). A histological diagnosis of HSIL was more frequently observed in HPV‐positive cases with a diagnosis of parakeratosis on cytology than in cases without parakeratosis (P = 0.8).

Conclusion

Our results demonstrate that a finding of parakeratosis on an otherwise negative Pap smear supports a follow‐up HPV DNA test. Also we should consider whether the presence of parakeratosis should be included in standard cytology reports. Additionally parakeratosis trended toward increased frequency of HSIL in follow‐up biopsy specimens. But it did not reach statistical significance. That is why larger studies are necessary to evaluate the association of parakeratosis and HSIL in colposcopic biopsy specimens. Diagn. Cytopathol. 2017;45:297–302. © 2016 Wiley Periodicals, Inc.
Iron(III) Pincer Complexes as a Strategy for Anticancer Studies
Authors: Estrada‐Montaño Aldo S. , Ryabov Alexander D. , Gries Alexandre , Gaiddon Christian , Le Lagadec Ronan
Published: February 2017

[Fe(NCN)2]PF6 (1·PF6) [NCHN = 1,3‐di(pyridin‐2‐yl)benzene] was readily obtained by a transmetalation reaction between [Fe3(CO)12] and Hg(NCN)Cl followed by a metathesis reaction with KPF6. X‐ray diffraction, electron paramagnetic resonance spectroscopy, and cyclic voltammetry studies confirmed the proposed structure. Cytotoxic assays in human colon cancer (HCT‐15), lung cancer (SKLU), and gastric cancer (AGS, KATOIII) cells were performed, and the IC50 data obtained for all cell lines showed that 1·PF6 has a much higher activity than cisplatin.
Analysis of transcriptional responses of normalizing genes on Crassostrea brasiliana under different experimental conditions
Authors: Müller Gabrielle do Amaral e Silva , de Lima Daína , Zacchi Flávia Lucena , Piazza Rômi Sharon , Lüchmann Karim Hahn , Mattos Jacó Joaquim , Schlenk Daniel , Bainy Afonso Celso Dias
Published: February 2017

Bivalves show remarkable plasticity to environmental changes and have been proposed as sentinel organisms in biomonitoring. Studies related to transcriptional analysis using quantitative real-time polymerase chain reaction (qRT-PCR) in these organisms have notably increased, imposing a need to identify and validate adequate reference genes for an accurate and reliable analysis. In the present study, 9 reference genes were selected from transcriptome data of Crassostrea brasiliana to identify their suitability as qRT-PCR normalizer genes. The transcriptional patterns were analyzed in gills of oysters under 3 different conditions: different temperatures (18, 24, or 32 °C) and phenanthrene (100 µg L−1) combined exposure; different salinities (10, 25, or 35‰) and phenanthrene combined exposure; and 10% of diesel fuel water-accommodated fraction (diesel-WAF) exposure. Reference gene stability was calculated using 5 algorithms (geNorm, NormFinder, BestKeeper, ΔCt, RefFinder). Transcripts of ankyrin-like (ANK), glyceraldehyde 3-phosphate dehydrogenase-like (GAPDH), and α-tubulin-like (TUBA) genes showed minor changes in different temperature/phenanthrene treatment. Transcripts of ANK, β-actin-like, and β-tubulin-like genes showed better stability at salinity/phenanthrene treatment, and ANK, TUBA, and 28S ribosomal protein-like genes showed the most stable transcription pattern in oysters exposed to diesel-WAF exposure. The present study constitutes the first systematic analysis of reference gene selection for qRT-PCR normalization in C. brasiliana. These genes could be employed in studies using qRT-PCR analysis under similar experimental conditions. Environ Toxicol Chem 2017;36:2190–2198. © 2017 SETAC
Venous Irritation Related to Intravenous Administration of Phenytoin versus Fosphenytoin
Authors: Jamerson Brenda D. , Dukes George E. , Brouwer Kim L.R. , Dorm Karl H. , Messenheimer John A. , Powell J. Robert
Published: February 2017

Study Objective. To compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water‐soluble phenytoin prodrug.

Design. Randomized, double‐blind, two‐period, crossover study.

Setting. University hospital clinical research unit.

Patients. Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment.

Interventions. Volunteers randomly received a 30‐minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14–21 days later.

Measurements and Main Results. Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p<0.05); cording occurred in six subjects. The time course of phenytoin‐induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording.

Conclusions. Fosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water‐soluble phenytoin prodrug should minimize the frequency and severity of infusion‐site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.
Hypertension and Left Ventricular Hypertrophy: Is Drug Therapy Beneficial?
Authors: Eselin Julie A. , Carter Barry L.
Published: February 2017

Left ventricular hypertrophy (LVH) is a consequence of long‐standing hypertension and is considered to be an independent risk factor for cardiovascular morbidity and mortality. Several antihypertensive agents are capable of inducing regression of LVH, but it is not known which class of drugs is most effective. The impact of drug‐induced reversal of hypertrophy on ventricular function remains a controversial issue. Furthermore, the long‐term clinical benefits of LVH regression have yet to be documented. Controversies also exist regarding the clinical outcomes associated with drug‐induced LVH regression.
An Alternative Sodium Bicarbonate Regimen During Cardiac Arrest and Cardiopulmonary Resuscitation in a Canine Model
Authors: Bleske Barry E. , Rice Ted L. , Warren Eric W.
Published: February 2017

We evaluated the effect of frequent, early bolus administration of low‐dose sodium bicarbonate (NaHCO3) on blood gas values during ventricular fibrillation and cardiopulmonary resuscitation (CPR) compared with normal saline and standard bolus doses of NaHCO3. This was a randomized laboratory investigation involving 13 mongrel dogs and 18 experiments (5 dogs were used in a crossover manner). Each dog underwent 3 minutes of ventricular fibrillation, followed by 15 minutes of CPR. Animals were randomly assigned to one of three treatments administered early in the resuscitation effort: NaHCO3 0.5 mEq/kg at 5, 10, and 15 minutes of ventricular fibrillation (SB); NaHCO3 1 mEq/kg at 5 minutes and 0.5 mEq/kg at 15 minutes of fibrillation (B); or 0.9% NaCl 1 ml/kg at 5 minutes and 0.5 ml/kg at 15 minutes of fibrillation (P). A total of 15 experiments were included for analysis. Arterial and venous blood gases were sampled at 4, 8, 13, and 18 minutes of fibrillation. The SB group demonstrated the highest arterial partial pressures of carbon dioxide (pCO2) at each sampling point after NaHCO3, including the 18‐minute sample: 42 ± 12, 29 ± 11, and 35 ± 10 torr for SB, P, and B, respectively. In addition, SB produced arterial alkalemia (pH > 7.45) after NaHCO3 administration. The arterial pH at 18 minutes of fibrillation for SB, P, and B was 7.46 ± 0.14, 7.29 ± 0.07, and 7.41 ± 0.1, respectively. Similar trends for pCO2 and pH were observed for venous samples. Early, frequent administration of low‐dose NaHCO3 during CPR is associated with elevated pCO2 and pH (alkalotic) values that may be potentially detrimental in this setting. It appears that this mode of administration offers no advantage over B with regard to blood gas values during CPR in this canine model.
Angioedema and Urticaria Associated With Omeprazole Confirmed by Drug Rechallenge
Authors: Bowlby Holly A. , Dickens George R.
Published: February 2017

Omeprazole is a substituted benzimidazole that has gained widespread use in the treatment of acidic and peptic ulcer disease. Adverse events with the drug are rare and involve mainly the gastrointestinal and central nervous systems. Skin inflammation, urticaria, pruritus, alopecia, and dry skin have been reported in 0.5–1.5% of patients. To date, no published report has linked angioedema with omeprazole. We report a case of a 34‐year‐old woman with cellulitis, ulcerative erosive esophagitis, and gastric and duodenal ulcers who developed several hypersensitivity reactions characterized by shortness of breath, wheezing, cough, mild angioedema, and total body urticaria and pruritus. These symptoms correlated with the addition of omeprazole to her regimen and the timing of its administration. A previous case report prompted a rechallenge with enteric‐coated omeprazole granules removed from the capsule shell. Recurrence of the adverse events suggested an allergy to the drug itself and not the capsule. Angioedema can be a life‐threatening allergic reaction requiring immediate treatment. Rechallenge using omeprazole with or without the capsule shell should be done only in a hospital setting where prompt action can be taken in the event of an emergency.
Febrile Reaction Associated With Urokinase
Authors: Shibley Michelle H. , Clifton G. Dennis
Published: February 2017

Urokinase is an endogenously produced human proteolytic enzyme used to treat many thrombotic disorders. A 54‐year‐old man with recurrent myocardial infarction experienced fever during intracoronary urokinase infusion into a saphenous vein graft; the fever resolved after discontinuation of the infusion. After excluding all other possible etiologies of fever, urokinase was determined to be the cause. Several studies indicated that this reaction may be associated with urokinase infusion, but it is actually recognized by few individuals. This is the first published case report of the adverse event to our knowledge.
Heterogeneous dielectric generalized Born model with a van der Waals term provides improved association energetics of membrane‐embedded transmembrane helices
Authors: Dutagaci Bercem , Sayadi Maryam , Feig Michael
Published: February 2017

The heterogeneous dielectric generalized Born (HDGB) implicit membrane formalism is extended by the addition of a van der Waals dispersion term to better describe the nonpolar components of the free energy of solvation. The new model, termed HDGBvdW, improves the energy estimates in the hydrophobic interior of the membrane, where polar and charged species are rarely found and nonpolar interactions become significant. The implicit van der Waals term for the membrane environment extends the model from Gallicchio et al. (J. Comput. Chem. 2004, 25, 479) by combining separate contributions from each of the membrane components. The HDGBvdW model is validated with a series of test cases ranging from membrane insertion and pair association profiles of amino acid side chain analogs and transmembrane helices. Overall, the HDGBvdW model leads to increased agreement with explicit membrane simulation results and experimental data. © 2016 Wiley Periodicals, Inc.
An averaged polarizable potential for multiscale modeling in phospholipid membranes
Authors: Witzke Sarah , List Nanna Holmgaard , Olsen Jógvan Magnus Haugaard , Steinmann Casper , Petersen Michael , Beerepoot Maarten T. P. , Kongsted Jacob
Published: February 2017

A set of average atom‐centered charges and polarizabilities has been developed for three types of phospholipids for use in polarizable embedding calculations. The lipids investigated are 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine, 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine, and 1‐palmitoyl‐2‐oleoyl‐sn‐glycerol‐3‐phospho‐L‐serine given their common use both in experimental and computational studies. The charges, and to a lesser extent the polarizabilities, are found to depend strongly on the molecular conformation of the lipids. Furthermore, the importance of explicit polarization is underlined for the description of larger assemblies of lipids, that is, membranes. In conclusion, we find that specially developed polarizable parameters are needed for embedding calculations in membranes, while common non‐polarizable point‐charge force fields usually perform well enough for structural and dynamical studies. © 2017 Wiley Periodicals, Inc.
Efficient gaussian density formulation of volume and surface areas of macromolecules on graphical processing units
Authors: Zhang Baofeng , Kilburg Denise , Eastman Peter , Pande Vijay S. , Gallicchio Emilio
Published: February 2017

We present an algorithm to efficiently compute accurate volumes and surface areas of macromolecules on graphical processing unit (GPU) devices using an analytic model which represents atomic volumes by continuous Gaussian densities. The volume of the molecule is expressed by means of the inclusion–exclusion formula, which is based on the summation of overlap integrals among multiple atomic densities. The surface area of the molecule is obtained by differentiation of the molecular volume with respect to atomic radii. The many‐body nature of the model makes a port to GPU devices challenging. To our knowledge, this is the first reported full implementation of this model on GPU hardware. To accomplish this, we have used recursive strategies to construct the tree of overlaps and to accumulate volumes and their gradients on the tree data structures so as to minimize memory contention. The algorithm is used in the formulation of a surface area‐based non‐polar implicit solvent model implemented as an open source plug‐in (named GaussVol) for the popular OpenMM library for molecular mechanics modeling. GaussVol is 50 to 100 times faster than our best optimized implementation for the CPUs, achieving speeds in excess of 100 ns/day with 1 fs time‐step for protein‐sized systems on commodity GPUs. © 2017 Wiley Periodicals, Inc.
Sec16 in conventional and unconventional exocytosis: Working at the interface of membrane traffic and secretory autophagy?
Authors: Tang Bor Luen
Published: February 2017

Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex‐mediated ER exit. Recent findings have, however, pointed toward a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α‐integrin in certain contexts of Drosophila development. In this regard, Sec16 interacts with components of a recently deciphered pathway of stress‐induced unconventional exocytosis, which is dependent on the tether protein Golgi reassembly stacking proteins (GRASPs) and the autophagy pathway. Intriguingly, Sec16 also appears to be post‐translationally modified by autophagy‐related signaling processes. Sec16 is known to be phosphorylated by the atypical extracellular signal regulated kinase 7 (Erk7) upon serum and amino acid starvation, both represent conditions that trigger autophagy. Recent work has also shown that Sec16 is phosphorylated, and thus regulated by the prominent autophagy‐initiating Unc‐51‐like autophagy activating kinase 1 (Ulk1), as well as another autophagy modulator Leucine‐rich repeat kinase 2 (Lrrk2). The picture emerging from Sec16's network of physical and functional interactors allows the speculation that Sec16 is situated (and may in yet undefined ways function) at the interface between COPII‐mediated exocytosis of conventional vesicular traffic and the GRASP/autophagy‐dependent mode of unconventional exocytosis.
IL‐10 expression in macrophages from neonates born from obese mothers is suppressed by IL‐4 and LPS/INFγ
Authors: Cifuentes‐Zúñiga Francisca , Arroyo‐Jousse Viviana , Soto‐Carrasco Gustavo , Casanello Paola , Uauy Ricardo , Krause Bernardo J. , Castro‐Rodríguez José A.
Published: February 2017

Obese women offspring have a higher risk of developing chronic diseases associated with an altered immune function. We aim to determine, in neonatal monocyte‐derived macrophages, whether maternal obesity is associated with an altered expression and DNA methylation of pro‐ and anti‐inflammatory genes, along with a higher pro‐inflammatory response. Cord blood from newborns of obese (Ob) and lean (control) women were obtained at delivery. Monocytes were isolated and differentiated into macrophages, in which M1 (LPS/IFNγ) and M2 (IL‐4) polarization were assayed. The mRNA levels for TNFα, IL‐1β, IL‐12A, IL‐12B, IL‐10, and IL‐4R were quantified by qPCR and the DNA methylation of candidate genes determined by pyrosequencing. Results: Ob‐monocytes had decreased levels of mRNA for pro‐inflammatory cytokines IL‐1β, IL‐10, and IL‐12B compared with controls. Conversely, Ob‐macrophages showed increased levels of mRNA for TNFα, IL‐4R, and IL‐10 compared with controls. M1 response was comparable between both groups, characterized by an important induction of TNFα and IL‐1β. In response to an M2 stimulus, control macrophages showed a decreased expression of inflammatory mediators while Ob‐macrophages had an additional suppression of the anti‐inflammatory mediator IL‐10. Changes in IL‐1β (monocytes) and IL‐10 (macrophages) in Ob‐monocytes were paralleled by changes in their promoter DNA methylation in fetal monocytes. These results suggest that monocyte‐derived macrophages from obese newborns show a basal anti‐inflammatory phenotype with an unbalanced response to M1 and M2 polarization stimuli. The presence of changes in DNA methylation of key inflammatory genes in neonatal monocytes suggests an intrauterine programing of immune function by maternal obesity.
Quantification of neonatal lung parenchymal density via ultrashort echo time MRI with comparison to CT
Authors: Higano Nara S. , Fleck Robert J. , Spielberg David R. , Walkup Laura L. , Hahn Andrew D. , Thomen Robert P. , Merhar Stephanie L. , Kingma Paul S. , Tkach Jean A. , Fain Sean B. , Woods Jason C.
Published: February 2017

Purpose

To demonstrate that ultrashort echo time (UTE) magnetic resonance imaging (MRI) can achieve computed tomography (CT)‐like quantification of lung parenchyma in free‐breathing, non‐sedated neonates. Because infant CTs are used sparingly, parenchymal disease evaluation via UTE MRI has potential for translational impact.

Materials and Methods

Two neonatal control cohorts without suspected pulmonary morbidities underwent either a research UTE MRI (n = 5; 1.5T) or a clinically‐ordered CT (n = 9). Whole‐lung means and anterior–posterior gradients of UTE‐measured image intensity (arbitrary units, au, normalized to muscle) and CT‐measured density (g/cm3) were compared (Mann–Whitney U‐test). Separately, a diseased neonatal cohort (n = 5) with various pulmonary morbidities underwent both UTE MRI and CT. UTE intensity and CT density were compared with Spearman correlations within ∼33 anatomically matched regions of interest (ROIs) in each diseased subject, spanning low‐ to high‐density tissues. Radiological classifications were evaluated in all ROIs, with mean UTE intensities and CT densities compared in each classification.

Results

In control subjects, whole‐lung UTE intensities (0.51 ± 0.04 au) were similar to CT densities (0.44 ± 0.09 g/cm3) (P = 0.062), as were UTE (0.021 ± 0.020 au/cm) and CT (0.034 ± 0.024 [g/cm3]/cm) anterior–posterior gradients (P = 0.351). In diseased subjects' ROIs, significant correlations were observed between UTE and CT (P ≤0.007 in each case). Relative differences between UTE and CT were small in all classifications (4–25%).

Conclusion

These results demonstrate a strong association between UTE image intensity and CT density, both between whole‐lung tissue in control patients and regional radiological pathologies in diseased patients. This indicates the potential for UTE MRI to longitudinally evaluate neonatal pulmonary disease and to provide visualization of pathologies similar to CT, without sedation/anesthesia or ionizing radiation.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2017;46:992–1000.
Changes to radiotherapy utilisation in Western NSW after the opening of a local service
Authors: Butler Sally M.
Published: February 2017

Introduction

In 2011, the first radiotherapy centre in Western NSW Local Health District (WNSWLHD) was opened in the city of Orange. Prior to this, patients travelled outside the health service, primarily to Sydney, to receive treatment. The aim of this study was to investigate if the establishment of the new rural radiotherapy service has changed the demographic profile, cancer type, treatment intent and number of patients treated.

Methods

Data were collected on WNSWLHD patients, 17 years of age and above, who received radiotherapy in either 2010 or 2012 in New South Wales (NSW) or Australian Capital Territory (ACT). The age, gender, treatment intent, cancer type and residential town were recorded.

Results

The number of patients who accessed radiation increased from 573 to 667 between 2010 and 2012. The corresponding radiotherapy utilisation (RTU) rates were 29.3% in 2010 and 33.4% in 2012, an improvement of 4.1% (P = 0.01, 95% CI 1–7%). Patients travelled 128.5 km less for treatment in 2012 than in 2010 (338.7 km vs. 210.2 km, CI 111–145.5 km, P > 0.0001). All regions had an improvement in the RTU rates apart from the Remote region which decreased by 9% (31–20% in 2012). The number of palliative treatments increased significantly only within the Orange region. The number of male patients for treatments also significantly increased as there were 81 additional treatments (292 vs. 373) as did patients with a respiratory cancer (66 vs. 97).

Conclusions

A new radiotherapy service in a sparsely populated health district significantly changed the pattern of radiotherapy use for those who lived only in the Orange region. Treatment capacity at the Orange radiotherapy centre has doubled with the opening of a second linear accelerator since this study was conducted. Thus, a follow‐up study is recommended to ascertain if radiotherapy rates remain low in the regions beyond Orange.
Prochlorococcus in the lab and in silico: The importance of representing exudation
Authors: Grossowicz Michal , Roth‐Rosenberg Dalit , Aharonovich Dikla , Silverman Jacob , Follows Michael J. , Sher Daniel
Published: February 2017

In this study, we test the applicability of the Droop/Caperon internal stores model to describe the growth and decline of the globally abundant marine cyanobacterium Prochlorococcus in batch culture as a function of internal and external inorganic and organic carbon and nitrogen. A rigorous parameter fitting exercise, constrained by the measured cell density, ammonium and inorganic carbon concentrations, revealed many different combinations of parameter values that provided equally good model‐data fit. Introducing data on C : N ratio from the published literature provided additional constraints which could only be satisfied with a structural change to the model. The simplest addition that satisfied these constraints and improved quantitative overall model‐data agreement was to explicitly represent excretion, which was predicted to account for 0.03–8.5% of the daily primary productivity; somewhat lower than previous estimates based on radiotracer incorporation. We argue that this significant and biologically meaningful process should not be neglected in models of marine phytoplankton.
A tale of pipes and reactors: Controls on the in‐stream dynamics of dissolved organic matter in rivers
Authors: Casas‐Ruiz Joan P. , Catalán Núria , Gómez‐Gener Lluís , von Schiller Daniel , Obrador Biel , Kothawala Dolly N. , López Pilar , Sabater Sergi , Marcé Rafael
Published: February 2017

The potential for rivers to alter the flux of dissolved organic matter (DOM) from land to ocean is widely accepted. Yet anticipating when and where rivers behave as active reactors vs. passive pipes of DOM stands as a major knowledge gap in river biogeochemistry, resulting in uncertainties for global carbon models. Here, we investigate the controls on in‐stream DOM dynamics by evaluating changes in DOM concentration and composition along several reaches of a medium‐sized river network over one full hydrological year. Roughly half of the observations over time and space showed active reactor conditions and, among these, similar proportion of gains and losses was measured. High water residence times promoted the active over passive behavior of the reaches, while DOM properties and nitrate availability determined whether they supplied or removed DOM from the river. Among different DOM fractions, protein‐like DOM both of terrestrial and aquatic origin seemed to drive bulk DOM patterns. Our study emphasizes the role of water residence time as a physical constraint for in‐stream processes, and provides new insights into the key factors governing the net balance between in‐stream gains and losses of DOM in rivers.
Distribution of trans‐resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver
Authors: Menet Marie‐Claude , Baron Stephanie , Taghi Meryam , Diestra Remi , Dargère Delphine , Laprévote Olivier , Nivet‐Antoine Valérie , Beaudeux Jean‐Louis , Bédarida Tatiana , Cottart Charles‐Henry
Published: February 2017

Scope

Trans‐resveratrol is widely studied for its potentially beneficial effects on numerous disorders. It is rapidly metabolized and its metabolites can exhibit biological activity. The present study aimed to investigate whether acute or sustained trans‐resveratrol administration impacted on the distribution of trans‐resveratrol and its metabolites in brain, heart, and liver.

Methods and results

We used ultra‐HPLC quadrupole‐TOF (UHPLC‐Q‐TOF) in a full‐scan mode to identify and assess large numbers of resveratrol metabolites. For acute intake, mice were overfed with a single dose of trans‐resveratrol (150 mg/kg) and organs were collected after 30 and 60 min. For sustained intake, trans‐resveratrol was given in the chow (0.04% w/w corresponding to 40 mg/kg/day), and plasma and the organs were collected after 3 months of this resveratrol diet. We found that trans‐resveratrol‐3‐O‐glucuronide and resveratrol‐3‐sulfate were the main metabolites found after acute intake, and free trans‐resveratrol (in the brain and heart) and dihydroresveratrol derivatives were found after sustained administration

Conclusions

Our results show notable differences between acute and sustained administration of trans‐resveratrol and distribution of trans‐resveratrol and its metabolites in mouse heart, brain, and liver. The results suggest a strategy for development of galenic forms of resveratrol.
Metabolically healthy obesity and incident chronic kidney disease: The role of systemic inflammation in a prospective study
Authors: Lin Lin , Peng Kui , Du Rui , Huang Xiaolin , Lu Jieli , Xu Yu , Xu Min , Chen Yuhong , Bi Yufang , Wang Weiqing
Published: February 2017

Objective

To investigate the association between the metabolically healthy obesity (MHO) phenotype and incident chronic kidney disease (CKD) in a Chinese population and whether systemic inflammation affects this association.

Methods

A cohort study was performed with 2,491 Chinese adults. Body mass index ≥ 25.0 kg/m2 was defined as obesity. CKD was defined as estimated glomerular filtration rate < 60 mL/min per 1.73 m2 or urinary albumin‐to‐creatinine ratio ≥ 30 mg/g. High‐sensitivity C‐reactive protein (hsCRP) was used as a surrogate marker of systemic inflammation.

Results

Over a median follow‐up period of 3.9 years, 243 of 2,491 participants developed incident CKD (9.8%). Compared with metabolically healthy nonobesity (MHNO), MHO was associated with incident CKD (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.01‐2.69), but not after adjustment for hsCRP. The MHO/hsCRP ≥ 0.20 mg/L group, but not the MHO/hsCRP < 0.20 mg/L group, had an increased OR for incident CKD (OR = 2.66, 95% CI 1.37‐5.14), with the MHNO/hsCRP < 0.20 mg/L group as the reference.

Conclusions

MHO was significantly associated with incident CKD, and the level of systemic inflammation partially explained this association.
Effect of chemical modification on the thermal and rheological properties of polylactide
Authors: Göttermann Svenja , Standau Tobias , Weinmann Sandra , Altstädt Volker , Bonten Christian
Published: February 2017

Today PLA is one of the most important bioplastics on the market. A disadvantage of commercial polylactide is that it is not readily foamable, due to its low molecular weight, its low melt stability, and the lack of strain hardening effects. Therefore, commercially available polylactide has to be modified. In this study, the effects on properties by adding different modifiers were investigated. Adding of the modifiers and their chemical reaction were performed by means of reactive extrusion on a twin screw extruder. The molecular weight was increased by modifiers, which can be attributed to a changed chain topology. The highest molecular weight was achieved with organic peroxide. The rheological studies show that a changed chain topology can be assumed for the modified PLA. The most pronounced effect on the melt properties—the melt viscosity and also the melt strength—again was observed with the organic peroxide. The melt strength was increased for PLA modified with the organic peroxide. Furthermore, the organic peroxide was the only modifier that enhanced the crystallization rate, which is also favorable for extrusion foaming. POLYM. ENG. SCI., 57:1242–1251, 2017. © 2017 Society of Plastics Engineers