bluuebunny/crossref_metadata_2025 huggingface dataset:
Avaliação Neuropsicológica na Doença Alzheimer e Demência Frontotemporal: critérios nosológicos
Authors: Hamdan Amer Cavalheiro , Ramos Ari Alex
Published: August 2016

A Doença de Alzheimer (DA) e a Demência Frontotemporal (DFT) são manifestações frequentemente observadas na prática clínica em avaliação neuropsicológica no idoso. Contudo, a similaridade dessas manifestações impõe uma dificuldade para estabelecer quais são os critérios diagnósticos diferenciais. O objetivo deste artigo é descrever os principais critérios nosológicos para a DA e para a DFT. A neurofisiopatologia é um marcador evidente nessa distinção. Uma plena compreensão nosológica nos distintos quadros demências é importante para a avaliação neuropsicológica.
A Novel Algorithm for Isolated Weber B Ankle Fractures: A Retrospective Review of 51 Nonsurgically Treated Patients
Authors: Holmes James R. , Acker William B. , Murphy Joshua M. , McKinney Amy , Kadakia Anish R. , Irwin Todd A.
Published: August 2016

Introduction: Stability of isolated Weber B ankle fractures can be difficult to determine. Using weight-bearing radiographs, a reliable method to determine the stability of isolated Weber B ankle fractures is described.

Methods: A retrospective review of prospectively gathered data was performed. Weber B ankle fractures were defined as stable when having a medial clear space (MCS) of <7 mm on initial gravity stress radiographs and a normal mortise relationship on weight-bearing radiographs. Fifty-one patients meeting these criteria were treated nonsurgically with protected weight bearing and serial radiography for 1 year.

Results: Average functional score results were: American Orthopaedic Foot and Ankle Society Hindfoot, 93.2; Foot and Ankle Ability Measure for Activities of Daily Living, 93.2; Olerud-Molander Ankle Score, 91.0; and visual analog scale pain score, 0.57. Despite a mean gravity stress MCS of 4.42 mm, no patient demonstrated subsequent MCS widening. Mean MCS on 1-year follow-up weight-bearing radiographs was 2.64 mm.

Conclusion: Weight-bearing ankle radiographs are predictive of stability in isolated Weber B ankle fractures. Gravity stress radiographs using traditional measurement criteria may overestimate instability in these injuries. Nonsurgical treatment with protected weight bearing shows good early outcomes.

Level of Evidence: IV
Computer Literacy and Online Learning Attitude toward GSOE Students in Distance Education Programs
Authors: Li Lung-Yu , Lee Long-Yuan
Published: August 2016

The purpose of this study was to explore graduate students’ competencies in computer use and their attitudes toward online learning in asynchronous online courses of distance learning programs in a Graduate School of Education (GSOE) in Taiwan. The research examined the relationship between computer literacy and the online learning attitudes of these students. Data were collected via a survey through 252 GSOE students in Taiwan. Results revealed a significant positive relationship between computer literacy and online learning attitude among the students. Higher computer literacy was correlated with higher online learning attitude. However, no statistically significant difference was found in online learning attitude by gender or by age group. Suggestions and managerial implications were discussed in the study, and would provide contribution both to the body of knowledge in the filed of education management.
Effect of direction of an external force on crystallization of colloidal particles in a V-shaped groove by sedimentation
Authors: Sato Masahide
Published: August 2016

We carried out Langevin dynamics simulations to study the effect of the direction of a uniform external force on the crystallization of colloidal particles in a V-shaped groove. When the inclination of the side walls of a groove was set to a suitable value and the external force bisected the angle, the face-centered-cubic (fcc) structure grew with a {100} growth interface. When the external force was inclined, the number of solidified particles decreased with increasing inclination, which is different from the growth in an inverted pyramidal container.
Impact of micro‐environmental changes on respiratory tract infections with intracellular bacteria
Authors: Shima Kensuke , Coopmeiners Jonas , Graspeuntner Simon , Dalhoff Klaus , Rupp Jan
Published: August 2016

Community‐acquired pneumonia is caused by intra‐ and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro‐environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon‐γ levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body.
Forcings of nutrient, oxygen, and primary production interannual variability in the southeast Atlantic Ocean
Authors: Bachèlery M.‐L. , Illig S. , Dadou I.
Published: August 2016

The recurrent occurrences of interannual warm and cold events along the coast of Africa have been intensively studied because of their striking effects on climate and fisheries. Using sensitivity experimentation based on a coupled physical/biogeochemical model, we show that the oceanic remote equatorial forcing explains more than 85% of coastal interannual nitrate and oxygen fluctuations along the Angolan and Namibian coasts up to the Benguela Upwelling System (BUS). These events, associated with poleward propagations of upwelling and downwelling Coastal Trapped Waves (CTW), are maximum in subsurface and controlled by physical advection processes. Surprisingly, an abrupt change in the CTW biogeochemical signature is observed in the BUS, associated with mixed vertical gradients due to the strong local upwelling dynamics. Coastal modifications of biogeochemical features result in significant primary production variations that may affect fisheries habitats and coastal biodiversity along the southwestern African coasts and in the BUS.
Assessing uncertainties in the Noah‐MP ensemble simulations of a cropland site during the Tibet Joint International Cooperation program field campaign
Authors: Zhang Guo , Chen Fei , Gan Yanjun
Published: August 2016

Despite the widespread use of the latest community Noah with multiparameterization (Noah‐MP) land surface model, it has not been rigorously evaluated over the complex Tibetan Plateau. This study assessed uncertainties in Noah‐MP simulations of a cropland site using observations from the 2008 Joint International Cooperation program field campaign. Such an assessment was conducted in the context of performing a total number of 4608 Noah‐MP physics ensemble simulations using two analysis methods: the natural selection approach and Tukey's test, where the impacts of uncertainties in atmospheric forcing conditions, vegetation parameters, and subprocesses on model simulations were identified. Uncertainty in precipitation data exerts greater influence on the general behavior of Noah‐MP ensemble simulations than that in the leaf area index (LAI). However, using a more realistic seasonal LAI improves the seasonal variations of surface heat fluxes. Combining a better precipitation forcing data set and Moderate Resolution Imaging Spectroradiometer monthly LAI significantly reduces the uncertainty range of the ensemble mean of surface heat fluxes. The uncertainty analysis results using the natural selection method are largely similar to that from Tukey's test but show some subtle differences. Both methods reveal greater uncertainties in the following subprocess schemes: canopy resistance, soil moisture threshold for evaporation, runoff and groundwater, and surface‐layer parameterization for this cropland site. The uncertainty analysis identifies the parameterization schemes that demonstrably degrade model performance. The uncertainties in ensemble simulations were significantly reduced when those schemes were excluded, and it was possible to configure an optimal combination of parameterization schemes to obtain similar performance to the ensemble mean of the “best” ensemble experiment.
Observations of conjugate MSTIDs using networks of GPS receivers in the American sector
Authors: Valladares C. E. , Sheehan R.
Published: August 2016

This study has used total electron content (TEC) values from an extended network of GPS receivers and a highly developed processing to characterize the conjugacy of medium‐scale traveling ionospheric disturbances (MSTIDs) over the American continent. It was found that midlatitude nighttime MSTIDs, also named electrobuoyancy waves, map into the opposite hemisphere but the amplitude of the TEC disturbance in the Southern Hemisphere is between 8 and 13% of the amplitude in the original hemisphere. The periods of the MSTIDs vary between 50 and 65 min. MSTID dynamics is presented for two days: 20 August 2012 and 17 June 2012. On the first day, MSTIDs entered into the American sector shortly before 4 UT, last for 3 h, drifted at an average speed of 200 m/s, and dissipated in the Caribbean region. In the Northern Hemisphere, the MSTIDs were directed southwestward (SW) and 60° from south. In the Southern Hemisphere, they moved northwestward (NW) or ~60° from north. The MSTID velocity changed through the night from ~300 m/s to ~150 m/s, but the propagation direction did not vary. On 17 June 2012 a series of wide MSTIDs were seen traveling across the Caribbean region that exited through the western coast of Central America. These MSTIDs last for ~5 h. Number density measured with the DMSP‐F15 and DMSP‐F17 satellites confirm the notion that the MSTIDs consist of rising and falling sheets of plasma density driven by electric fields likely set by a Perkins‐type instability. These observations support the notion that gravity waves can seed and boost the growth of the nighttime MSTIDs.
Influence of Nano‐Calcium Carbonate Particles on the Moisture Absorption and Mechanical Properties of Epoxy Nanocomposite
Authors: He Hongwei , Yang Jingjing , Huang Wei , Cheng Muhua
Published: August 2016

The moisture absorption and diffusion characteristics of epoxy‐based nanocomposites containing nano‐calcium carbonate (nano‐CaCO3) are investigated. Although the moisture absorption decreased with increasing nano‐CaCO3 content except for 8 wt%, the moisture absorption and diffusion behaviors were different from each other. It was found that the incorporation of 2 wt% and 4 wt% nano‐CaCO3 decreased moisture absorption capacity effectively. This is due to the more uniform distribution of nano‐CaCO3 particles, which created a longer diffusion path of moisture molecules in the nanocomposites. For the diffusion rate of moisture, there is no significant change observed on adding nano‐CaCO3. The effect of moisture absorption on the mechanical properties of nano‐CaCO3‐filled epoxy nanocomposites were investigated as a functional property of nano‐CaCO3 content. Due to moisture absorption, the flexural strength of epoxy/nano‐CaCO3 composites significantly impaired when compared to dry nanocomposites. However, the effect of nano‐CaCO3 on these mechanical properties was found to be positive, which allows the application of modified epoxy resin in high‐humidity environments.
Copper(I) oxide nanoparticles supported on magnetic casein as a bio‐supported and magnetically recoverable catalyst for aqueous click chemistry synthesis of 1,4‐disubstituted 1,2,3‐triazoles
Authors: Shaabani Shabnam , Tavousi Tabatabaei Azadeh , Shaabani Ahmad
Published: August 2016

Copper(I) oxide nanoparticles supported on magnetic casein (Cu2O/Casein@Fe3O4NPs) has been synthesized as a bio‐supported catalyst and was characterized using powder X‐ray diffraction, transmission electron microscopy, energy dispersive X‐ray and Fourier transform infrared spectroscopies, thermogravimetric analysis and inductively coupled plasma optical emission spectrometry. The catalytic activity of the synthesized catalyst was investigated in one‐pot three‐component reactions of alkyl halides, sodium azide and alkynes to prepare 1,4‐disubstituted 1,2,3‐triazoles with high yields in water. The reaction work‐up is simple and the catalyst can be magnetically separated from the reaction medium and reused in subsequent reactions.
Enhancing microbial production of biofuels by expanding microbial metabolic pathways
Authors: Yu Ping , Chen Xingge , Li Peng
Published: August 2016

Fatty acid, isoprenoid, and alcohol pathways have been successfully engineered to produce biofuels. By introducing three genes,atfA,adhE, andpdc, intoEscherichia colito expand fatty acid pathway, up to 1.28 g/L of fatty acid ethyl esters can be achieved. The isoprenoid pathway can be expanded to produce bisabolene with a high titer of 900 mg/L inSaccharomyces cerevisiae. Short‐ and long‐chain alcohols can also be effectively biosynthesized by extending the carbon chain of ketoacids with an engineered “+1” alcohol pathway. Thus, it can be concluded that expanding microbial metabolic pathways has enormous potential for enhancing microbial production of biofuels for future industrial applications. However, some major challenges for microbial production of biofuels should be overcome to compete with traditional fossil fuels: lowering production costs, reducing the time required to construct genetic elements and to increase their predictability and reliability, and creating reusable parts with useful and predictable behavior. To address these challenges, several aspects should be further considered in future: mining and transformation of genetic elements related to metabolic pathways, assembling biofuel elements and coordinating their functions, enhancing the tolerance of host cells to biofuels, and creating modular subpathways that can be easily interconnected.
Effect of DNA on the conformational dynamics of the endonucleases I‐DmoI as provided by molecular dynamics simulations
Authors: Grottesi Alessandro , Cecconi Simone , Molina Rafael , D'abramo Marco
Published: August 2016

The conformational behavior of the wild‐type endonucleases I‐DmoI and two of its mutants has been studied in the presence and in the absence of DNA target sequences by means of extended molecular dynamics simulations. Our results show that in the absence of DNA, the three protein forms explore a similar essential conformational space, whereas when bound to the same DNA target sequence of 25 base pairs, they diversify and restrain the subspace explored. In addition, the differences in the essential subspaces explored by the residues near the catalytic site for both the bound and unbound forms are discussed in background of the experimental protein activity.
Reductive Calcination of Mineral Magnesite: Hydrogenation of Carbon Dioxide without Catalysts
Authors: Baldauf‐Sommerbauer Georg , Lux Susanne , Aniser Wolfgang , Siebenhofer Matthäus
Published: August 2016

The conversion of mineral magnesite to magnesium oxide, methane, carbon dioxide, and carbon monoxide in a hydrogen atmosphere at ambient pressure and overpressure without catalysts is discussed. Low temperature and elevated pressure facilitate CH4 formation whereas moderate to high temperature and low pressure facilitate CO formation. Methane is formed directly without any additional catalyst. CO2 emissions are decreased substantially in reductive calcination. Additional experiments revealed that reductively calcined magnesium oxide is a highly active reverse water‐gas shift catalyst. CO formation from gaseous CO2 and H2 at catalytically active magnesium oxide was reproducibly confirmed. Further reduction of carbon monoxide to methane is not catalyzed by reductively calcined magnesium oxide.
Single‐Phase Flow Residence‐Time Distributions in a Rotor‐Stator Spinning Disc Reactor
Authors: Haseidl Franz , König Peter , Hinrichsen Olaf
Published: August 2016

Residence‐time experiments were used to study the single‐phase flow hydrodynamics of a rotor‐stator spinning disc reactor. Two reactor setups of different sizes were used to identify the effects of the operating parameters. To precisely determine the central moments of the transfer functions of the reactors, which allow conclusions on the fluid flow profiles in the gap between the moving and nonmoving parts, a deconvolution procedure in the time and frequency domains was established. Residence‐time models were compared with regard to their applicability for deconvolution and fitting. The spatial extent of the convectionally back‐mixed and the plug‐flow regions was quantified with a threshold method. The results were incorporated into an engineering model and compared to literature data.
Sol‐Gel and Porous Glass‐Based Silica Monoliths with Hierarchical Pore Structure for Solid‐Liquid Catalysis
Authors: Enke Dirk , Gläser Roger , Tallarek Ulrich
Published: August 2016

This work draws attention to both prospects and challenges for silica monoliths in solid‐liquid catalysis at ultrahigh efficiency. The fundamental advantages of silica monoliths as support structure over particulate fixed beds and organic‐polymer monoliths are illustrated as well as recent applications as flow‐through microreactors for the production of fine chemicals. Preparation routes to sol‐gel and porous glass‐based silica monoliths featuring a hierarchical pore structure are described and their potential use as short‐contact‐time reactors is highlighted together with a view on the multiscale characterization and their rational design by establishing quantitative synthesis‐morphology‐transport relationships.
Core‐shell structured CaO‐based pellets protected by mesoporous ceramics shells for high‐temperature CO2 capture
Authors: Sedghkerdar Mohammad Hashem , Mahinpey Nader , Soleimanisalim Amir H. , Sun Zhenkun , Chen Zhiwei , Lim Jim , Kaliaguine Serge
Published: August 2016

In this study, a series of core‐shell structured spheriform CO2 sorbents were synthesized by using CaO‐based pellets as cores and different mesoporous metal oxides (e.g. alumina, ceria, and yttrium‐stabilized zirconia) as shells through a repeated wet impregnation coating process. Cyclic CO2 capture performance of the obtained sorbents was investigated using a thermogravimetric analyzer. Among all the core/shell sorbents under study, the pellets coated with a layer of alumina exhibit the best performance in the retention of CO2 uptake over 20 cycles with the lowest activity loss of only 30.4 %, attributed to the existence of the thermal stable porous alumina shell which prevents the sintering and the aggregation of the CaO grains. Moreover, the attrition study using an air‐jet apparatus and a standard test method reveals that such sorbents exhibit enhanced attrition resistance due to the protection of the porous shell providing them with a great potential for application in fluidized bed conditions.
Enable cloud DevOps approach for industry and higher education
Authors: Airaj Mohammed
Published: August 2016

Innovation in both industry and academia increasingly depends on the fast evolution of software and software services. Adoption of agile software development methodologies has reduced time to market and improved success rates; however, deployment obstacles often impede the quick delivery of the new and improved features to end users. This paper deals with DevOps, a new methodology that extends agile processes to include operations. DevOps methodology adopted with cloud computing could immediately benefit current practitioners from various software development parties while a focus on the young will ensure that DevOps ideals and processes will be taken forward into the longer‐term future. Moving towards clouds, adopting DevOps culture, and implementing DevOps tools will produce more innovative services at lower cost and with higher quality. Wider adoption of the cloud DevOps will bring cloud DevOps features, and the benefit of agile software development, automation, and elastic resource provisioning. Additionally, teaching cloud DevOps in university will help to overcome the barriers to its adoption and maximize its indirect socioeconomic impact.
The Utility of Cannabidiol in the Treatment of Refractory Epilepsy
Authors: Reddy DS
Published: August 2016

Cannabis‐derived cannabinoids such as cannabidiol (CBD) have anticonvulsant properties. Recently, there has been an emerging interest in the use of CBD‐enriched products for treatment of drug‐resistant epilepsy. Some pilot trials of CBD have proved beneficial for refractory epilepsy, but its efficacy is yet to be confirmed by standard placebo‐controlled trials. However, the mechanisms underlying the seizure protection efficacy claims of CBD remain unclear. This review briefly describes the clinical utility of CBD in the treatment of refractory epilepsy.
Transporters affecting biochemical test results: Creatinine‐drug interactions
Authors: Chu X , Bleasby K , Chan GH , Nunes I , Evers R
Published: August 2016

Creatinine is eliminated by the kidneys through a combination of glomerular filtration and active transport. Drug‐induced increases in serum creatinine (SCr) and/or reduced creatinine renal clearance are used as a marker for acute kidney injury. However, inhibition of active transport of creatinine can result in reversible and, therefore, benign increases in SCr levels. Herein, the transporters involved in creatinine clearance are discussed, in addition to limitations of using creatinine as a biomarker for kidney damage.
Diagnostic utility of arborizing stromal meshwork fragments in mucinous tumors
Authors: Patadji Stell , Pantanowitz Joshua , Perlov Natalie M. , Monaco Sara E.
Published: August 2016

Introduction

Arborizing stromal meshwork fragments (ASMFs) have been proposed as a useful clue to differentiate mucin associated with mucinous adenocarcinoma from contaminating mucus during endobronchial ultrasound‐guided transbronchial needle aspiration. Our aim was to retrospectively review cytology cases with mucinous material to determine the utility of ASMFs in diagnosing mucinous tumors.

Material and Methods

Diff‐Quik stained smears from archival cytology cases (N = 40) were reviewed, including adenocarcinomas with mucinous features, cystic mucinous neoplasms, and control cases with mucin contamination. Specimens were procured by image‐guided fine needle aspiration (FNA) (16 cases), endoscopic ultrasound‐guided FNA (22 cases), pathologist‐performed FNA (1 case), and fluid drainage (1 case). All cases were reviewed for ASMFs, which were defined as metachromatic, spidery extensions with frayed edges within a background of mucinous material.

Results

ASMFs were identified in 4 (10% of cases, 14% of adenocarcinomas) cases of metastatic gastrointestinal mucinous adenocarcinomas in various locations (liver, lymph node, lung, and bone), but absent in mucin contamination. ASMFs in Diff‐Quik stained smears were magenta‐colored and corresponded to intervening stroma between dissecting mucin in the tumor. Nonarborizing desmoplastic stroma, inspissated mucus, cartilage fragments, transgressing vessels in renal cell carcinoma, and mucus‐like material in pancreatic pseudocysts can morphologically mimic ASMFs.

Conclusion

These data show that ASMFs may be encountered in some (14%) cases of adenocarcinoma with mucinous differentiation. When present, ASMFs can be diagnostically helpful to differentiate adenocarcinoma with mucinous features from contaminating mucus, if reliably distinguished from mimics. Diagn. Cytopathol. 2016;44:805–810. © 2016 Wiley Periodicals, Inc.
HPA axis dysregulation, NR3C1 polymorphisms and glucocorticoid receptor isoforms imbalance in metabolic syndrome
Authors: Martins Clarissa Silva , Elias Daniel , Colli Leandro Machado , Couri Carlos Eduardo , Souza Manoel Carlos L.A. , Moreira Ayrton C. , Foss Milton C. , Elias Lucila L.K. , de Castro Margaret
Published: August 2016

Context

Metabolic syndrome (MetS) shares several similarities with hypercortisolism.

Objectives

To evaluate hypothalamic‐pituitary‐adrenal (HPA) axis sensitivity to dexamethasone (DEX), NR3C1 single nucleotide polymorphisms (SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in peripheral immune cells of MetS patients and controls.

Design

Prospective study with 40 MetS patients and 40 controls was conducted at the Ribeirão Preto Medical School University Hospital.

Methods

Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5, and 1 mg of DEX given at 2300 h. In addition, p.N363S (rs6195), p.ER22/23EK (rs6189‐6190), and BclI (rs41423247) SNPs were evaluated by quantitative polymerase chain reaction allelic discrimination. Exons 3 to 9 and exon/intron boundaries of NR3C1 were sequenced. GR isoforms and cytokines (IL1B, IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα) expression were assessed by quantitative polymerase chain reaction.

Results

Plasma and salivary cortisol (nmol/L) after 1‐mg DEX were higher in MetS patients compared with controls (PF: 70.2 ± 17.3 vs 37.9 ± 2.6, P = .02, and SF: 4.9 ± 1.7 vs 2.2 ± 0.3, P < .0001). After all DEX doses, a lower number of MetS patients suppressed plasma and salivary cortisol compared with controls. The BclI genotypic frequencies (%) differed between patients (CC:56/CG:44) and controls (CC:50/CG:32.5/GG:17.5) (P = .03). The GRβ was overexpressed (fold = 100.0; P = .002) and IL4 (fold = −265.0; P < .0001) was underexpressed in MetS.

Conclusion

MetS patients exhibited decreased HPA sensitivity to glucocorticoid feedback. Moreover, the BclI polymorphism lower frequency, GRβ overexpression, and IL4 underexpression might underlie the molecular mechanism of glucocorticoid resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS pathogenesis.
A validated, sensitive HPLC‐MS/MS method for quantification of cis‐para‐methyl‐4‐methylaminorex (cis‐4,4'‐DMAR) in rat and human plasma: application to pharmacokinetic studies in rats
Authors: Lucchetti Jacopo , Marzo Claudio M. , Di Clemente Angelo , Cervo Luigi , Gobbi Marco
Published: August 2016

4,4′‐DMAR is an analogue of the known psychostimulants 4‐methylaminorex and aminorex. In the light of reports of deaths associated with its abuse, and the easy access from Internet vendors, the EU Council recently decided on control measures across member states. Here we describe a validated method for measuring plasma levels of cis‐4,4′‐DMAR, crucial for preclinical studies and analysis in human plasma. Chromatographic separation was done by gradient elution on a Kinetex C18 column with 0.1% formic acid in water and 0.1% formic acid in acetonitrile at 0.2 mL/min. Detection was by positive electrospray ionization (ESI+) in multiple reaction monitoring mode monitoring the quantifier transitions m/z 191.4 → m/z 148.3 for cis‐4,4'‐DMAR and m/z 259.3 → m/z 194.2 for carbamazepine (internal standard). Protein precipitation with 1% of formic acid in acetonitrile was used in cis‐4,4'‐DMAR extraction from plasma; recovery was high (>93%) with a negligible matrix effect. This method provides an accurate, precise, and sensitive method for cis‐4,4’‐DMAR quantification in human and rat plasma, following European Medicine Agency guidelines for bioanalytical method validation. Pharmacokinetic studies were conducted in rats. After an intravenous dose of 1 mg/kg, plasma levels declined rapidly (≥80% in 4 h), followed by a slow elimination phase (t1/2 of 5.14 ± 0.65 h). Absorption was rapid after intraperitoneal injection (tmax = 15 min) with a rapid decline thereafter; Cmax and AUC0‐240min showed dose‐proportionality over the dose range 1–10 mg/kg. This method was successfully applied to investigate pharmacokinetic properties in rats and could be used to quantify cis‐4,4’‐DMAR levels in human plasma. Copyright © 2016 John Wiley & Sons, Ltd.
Epigenetic suppression of potassium‐chloride co‐transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA)
Authors: Lin C.‐R. , Cheng J.‐K. , Wu C.‐H. , Chen K.‐H. , Liu C.‐K.
Published: August 2016

Background

Multiple mechanisms contribute to the stimulus‐evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium‐chloride co‐transporter 2 (KCC2) gene expression in the persistence of inflammatory pain.

Methods

Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl‐histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT‐PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection.

Results

Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)‐mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock‐down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour.

Conclusion

These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA.

Significance

Persistent pain suppresses KCC2 expression through HDAC‐mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic.
Putting pain out of mind with an ‘out of body’ illusion
Authors: Pamment J. , Aspell J.E.
Published: August 2016

Background

Chronic pain is a growing societal concern that warrants scientific investigation, especially given the ineffectiveness of many treatments. Given evidence that pain experience relies on multisensory integration, there is interest in using body ownership illusions for reducing acute pain.

Aim

In the present study, we investigate whether patients’ experience of chronic pain could be reduced by full body illusions (FBIs) that cause participants to dissociate from their own body.

Methods

Participants with chronic pain (including sciatica, osteoarthritis, fibromyalgia, muscular pain, IBS and back pain) viewed their own ‘virtual’ bodies via a video camera and head‐mounted display for two minutes. In the ‘back‐stroking FBI’, their backs were stroked with a stick while they viewed synchronous or asynchronous stroking on the virtual body and in the ‘front‐stroking FBI’, they were stroked near their collarbone while viewing the stick approach their field of view in a synchronous or asynchronous fashion. Illusion strength and pain intensity were measured with self‐report questionnaires.

Results

We found that full body illusions were experienced by patients with chronic pain and further, that pain intensity was reduced by an average of 37% after illusion (synchronous) conditions.

Conclusion

These findings add support to theories that high‐level multisensory body representations can interact with homeostatic regulation and pain perception.

Significance

Pain intensity in chronic pain patients was reduced by 37% by ‘out of body’ illusions. These data demonstrate the potential of such illusions for the management of chronic pain.
Charge‐based separation of particles and cells with similar sizes via the wall‐induced electrical lift
Authors: Thomas Cory , Lu Xinyu , Todd Andrew , Raval Yash , Tzeng Tzuen‐Rong , Song Yongxin , Wang Junsheng , Li Dongqing , Xuan Xiangchun
Published: August 2016

The separation of particles and cells in a uniform mixture has been extensively studied as a necessity in many chemical and biomedical engineering and research fields. This work demonstrates a continuous charge‐based separation of fluorescent and plain spherical polystyrene particles with comparable sizes in a ψ‐shaped microchannel via the wall‐induced electrical lift. The effects of both the direct current electric field in the main‐branch and the electric field ratio in between the inlet branches for sheath fluid and particle mixture are investigated on this electrokinetic particle separation. A Lagrangian tracking method based theoretical model is also developed to understand the particle transport in the microchannel and simulate the parametric effects on particle separation. Moreover, the demonstrated charge‐based separation is applied to a mixture of yeast cells and polystyrene particles with similar sizes. Good separation efficiency and purity are achieved for both the cells and the particles.
Investigation of UV/H2O2 pretreatment effects on humic acid fouling on polysulfone/titanium dioxide—And polysulfone/multiwall carbon nanotube—Nanocomposite ultrafiltration membranes
Authors: Koutahzadeh Negin , Esfahani Milad Rabbani , Stretz Holly A. , Arce Pedro E.
Published: August 2016

Membrane fouling is an important concern for membrane separation technology. Preparation of the feed before entering into the membrane and physicochemical modifications of membrane are both important approaches toward enhancing the permeability and separation in membrane processes. The present report combines both approaches. In terms of membrane characterization, scanning electron microscopy (SEM) images showed that the addition of titanium dioxide (TiO2) nanoparticles and multiwall carbon nanotube (MWCNT) resulted in increased pore numbers at the top surface and more interconnected pores in the porous membrane structure. The surface hydrophilicity and porosity of the PSF/TiO2 and PSF/MWCNT increased compared with pure PSF membranes. PSF/TiO2 nanocomposites showed just 10% flux decline and improved 95% flux recovery ratio (FRR%). UV/H2O2 pretreatment changed the physicochemical properties of humic acid (HA) aggregates by reducing the super‐micrometer size range (>1 μm) aggregates to a bimodal distribution of two submicrometer size ranges <1 μm (10–100 nm and 100–1000 nm) and increased the zeta potential of HA solution due to the production of new functional groups. The oxidation pretreatment alone improved flux decline at 120 min from 21% to 80% and increased the FRR from 58% to 80% for the pure PSF. The oxidative pretreatment also improved purification for the PSF/TiO2 nanocomposite membranes. The flux decline improved from 81% to 95% with only a slight improvement on the 94% FRR increasing to about 99% FRR. The FRR in the case of PSF/MWCNT actually declined with the pretreatment. The hybrid process of UV/H2O2 pretreatment and PSF/TiO2 nanocomposite membranes exhibited optimal permeability and antifouling properties. © 2016 American Institute of Chemical Engineers Environ Prog, 36: 27–37, 2017
The SAGES telephone neuropsychological battery: correlation with in‐person measures
Authors: Bunker Lydia , Hshieh Tammy T. , Wong Bonnie , Schmitt Eva M. , Travison Thomas , Yee Jacqueline , Palihnich Kerry , Metzger Eran , Fong Tamara G. , Inouye Sharon K.
Published: August 2016

Objective

Neuropsychological test batteries are administered in person to assess cognitive function in both clinical and research settings. However, in‐person administration holds a number of logistical challenges that makes it difficult to use in large or remote populations or for multiple serial assessments over time. The purpose of this descriptive study was to determine whether a telephone‐administered neuropsychological test battery correlated well with in‐person testing.

Methods

Fifty English‐speaking patients without dementia, over 70 years old, and part of a cohort of patients in a prospective cohort study examining cognitive outcomes following elective surgery were enrolled in this study. Five well‐validated neuropsychological tests were administered by telephone to each participant by a trained interviewer within 2–4 weeks of the most recent in‐person interview. Tests included the Hopkins Verbal Learning Test‐Revised, Digit Span, Category Fluency, Phonemic Fluency, and Boston Naming Test. A General Cognitive Performance composite score was calculated from individual subtest scores as a Z‐score.

Results

Mean age was 74.9 years (SD = 4.1), 66% female, and 4% non‐White. Mean and interquartile distributions of telephone scores were similar to in‐person scores. Correlation analysis of test scores revealed significant correlations between telephone and in‐person results for each individual subtest, as well as for the overall composite score. A Bland–Altman plot revealed no bias or trends in scoring for either test administration type.

Conclusions

In this descriptive study, the telephone version of a neuropsychological test battery correlated well with the in‐person version and may provide a feasible supplement in clinical and research applications. Copyright © 2016 John Wiley & Sons, Ltd.
Novel educational interventions in residency increase knowledge of chronic liver disease and career interest in hepatology
Authors: Mikolajczyk Adam E. , Farnan Jeanne M. , McConville John F. , Jensen Donald M. , Reddy K. Gautham , Te Helen S. , Reau Nancy , Aronsohn Andrew I.
Published: August 2016

There is an increasing burden of chronic liver disease (CLD) in the United States but a significant shortage of hepatologists. Thus, it is necessary to develop new recruitment strategies to the field of hepatology as well as ensure that non‐gastroenterology‐trained physicians are able to capably assist in the care of CLD. We established a novel, nonelective, inpatient hepatology rotation that uses required modules in the American Association for the Study of Liver Diseases Curriculum and Training‐First Hepatitis B and C curriculums as well as in LiverLearning. A paper‐based anonymous assessment was distributed to the inaugural 25 postgraduate years 2 and 3 internal medicine residents before and after the 2‐week rotation over the course of 1 year. Both the prerotation and postrotation assessments included validated multiple‐choice questions and Likert‐type questions, which evaluated self‐perceived knowledge and comfort with managing CLD. The mean comfort level (1 = not at all comfortable/strongly disagree, 5 = very comfortable/strongly agree) of managing several common liver diseases increased significantly after completion of the rotation (i.e., cirrhosis 2.8 versus 3.8, P < 0.001; hepatitis B 2.4 versus 3.4, P = 0.001; hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus 4.0, P < 0.001; liver transplant care 2.1 versus 3.4, P < 0.001). There was also a significantly increased interest in hepatology as a career (2.6 versus 3.0, P = 0.03). Finally, the mean percentage of multiple‐choice questions answered correctly on the pretest was 62% and posttest was 77% (P = 0.02). Conclusion: Our novel curriculum and nonelective hepatology rotation has effectively demonstrated improvement in internal medicine residents' comfort with and knowledge of CLD, and increased career interest in hepatology was also observed after completion of the curriculum, which suggests that more exposure to CLD could positively impact recruitment to the workforce; larger, multicenter studies are needed to validate these results. (Hepatology 2016;64:2210‐2218).
Cell autonomous or systemic EGFR blockade alters the immune‐environment in squamous cell carcinomas
Authors: Mascia Francesca , Schloemann Derek T. , Cataisson Christophe , McKinnon Katherine M. , Krymskaya Ludmila , Wolcott Karen M. , Yuspa Stuart H.
Published: August 2016

Targeting mutations and amplifications in the EGFR has been successful precision therapy for cancers of the lung, oral cavity and gastrointestinal track. However, a systemic immune reaction manifested by dose‐limiting inflammation in the skin and gut has been a consistent adverse effect. To address the possibility that intra‐tumoral immune changes contribute to the anti‐cancer activity of EGFR inhibition, squamous cancers were produced by syngeneic orthografts of either EGFR null or wildtype mouse primary keratinocytes transduced with an oncogenic H‐ras retrovirus. Flow cytometric, RNA and Bioplex immunoassay analyses of the tumor immune milieu were performed. Cancers forming from keratinocytes genetically depleted of EGFR were smaller than wildtype cancers and had fewer infiltrating FoxP3 Treg cells, lower Foxp3 RNA and a lower percentage of CD4 PD1 positive cells indicating a tumor cell autonomous regulation of its microenvironment. Hosts bearing wildtype cancers treated with gefitinib for 1 week showed a trend for smaller tumors. In this short term pharmacological model, there was also a trend to reduced FoxP3 cells and FoxP3 RNA in the tumors of treated mice as well as a substantial increase in the ratio of IL‐1A/IL‐1RA transcripts. These results suggest that relatively brief systemic inhibition of EGFR signaling alters the immune environment of the targeted cancer. Together these data imply that an EGFR dependent Treg function supports the growth of squamous cancers and is a target for the therapeutic activity of EGFR inhibition.
Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer
Authors: Takahashi Yayoi , Sugai Tamotsu , Habano Wataru , Ishida Kazuyuki , Eizuka Makoto , Otsuka Koki , Sasaki Akira , Takayuki Matsumoto  , Morikawa Takanori , Unno Michiaki , Suzuki Hiromu
Published: August 2016

Differences in the pathogenesis of microsatellite stable (MSS) sporadic colorectal cancers (CRCs) between left‐sided CRC (LC) and right‐sided CRC (RC) have not been clarified. To identify pathogenesis‐related genomic differences between MSS CRCs within the two locations, we performed a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability (MSI; high and low/negative) and DNA methylation status (low methylation epigenome; intermediate methylation epigenome [IME] or high methylation epigenome [HME]) were determined using polymerase chain reaction (PCR) microsatellite analysis and PCR‐bisulfite pyrosequencing, respectively. Additionally, mutations in the TP53, KRAS, BRAF and PIK3CA genes were examined using PCR‐bisulfite pyrosequencing (for KRAS and BRAF mutations) or PCR‐single conformation polymorphism (for TP53 and PIK3CA mutations), followed by sequencing of aberrant bands. Finally, a genome‐wide study using a copy number alteration (CNA)‐targeted single nucleotide polymorphism array was performed. Ninety‐two CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with the MSS phenotype (LC, 56; RC, 15). Mutations in KRAS were associated with RC with the MSS phenotype, whereas mutations in TP53 were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies of KRAS and TP53 mutations in the IME between LC and RC with the MSS phenotype. Although CNA gains were associated with LC with the MSS phenotype, CNA losses were not major alterations associated with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC.
The Role of Hox in Pisiform and Calcaneus Growth Plate Formation and the Nature of the Zeugopod/Autopod Boundary
Authors: Reno Philip L. , Kjosness Kelsey M. , Hines Jasmine E.
Published: August 2016

The mesopodium forms at the boundary between the zeugopod and autopod and is composed of short nodular bones that typically lack growth plates. Hoxa11 and Hoxa13 are expressed in mutually exclusive proximal‐distal domains that demarcate the zeugopod/autopod boundary. Similarly, Hoxd genes are deployed in two distinct phases during limb development. The early phase corresponds to proximal segments including the zeugopod, and a late phase occurs in the digits. This arrangement produces a gap of low Hoxd expression that is traditionally viewed to correspond to the mesopodium. In contrast to the other mesopodials, the mammalian pisiform and calcaneus form true growth plates. We show that these bones, along with other proximal mesopodials, develop within the Hoxa11 and Hoxd11 expression domains. We also observe that the pisiform growth plate becomes disorganized with Hoxa11 or Hoxd11 loss of function, indicating a direct role for Hox11 in its development. Hoxa13 loss of function has minimal effect on the pisiform and proximal calcaneus as these bones still form secondary centers and undergo longitudinal growth. Consideration of the phenotypes resulting from hypodactyly (Hd) and synpolydactyly homolog (spdh) mutations, which result from altered HOXA13 and HOXD13 proteins, respectively, confirms that Hox13 plays a limited role in the development of the pisiform and calcaneus and suggests that they lie within the early phase of Hox expression. Therefore, with respect to patterns of ossification and gene expression, these bones share much more in common with the zeugopod than the autopod. Such an interpretation fits with the timing of autopod origins during tetrapod evolution.
Interferon stimulated genes and innate immune activation following infection with hepatitis B and C viruses
Authors: Hayes C. Nelson , Chayama Kazuaki
Published: August 2016

Although not directly cytopathic, hepatitis B and C viruses (HBV and HCV) are responsible for millions of deaths per year, and the aging patient population presents a severe public health challenge. Most cases of acute HCV become chronic, but treatment has become increasingly successful following the development of direct acting antiviral agents. Conversely, most cases of acute HBV are cleared in the pre‐symptomatic stage and do not become chronic, but treatment options for chronic HBV are limited and rarely result in clearance. Despite these differences, interferon is partially effective against both viruses and has long been used in therapy. Newer treatments have largely moved away from interferon in favor of more targeted approaches, but interferon signaling remains the body's first line of defense against viruses. The recent discovery of type III interferon and IFNL4 has yielded new insights into the mechanism of ISG activation and revealed potential new therapeutic targets. J. Med. Virol. 89:388–396, 2017. © 2016 Wiley Periodicals, Inc.