bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapy response monitoring of the early effects of a new BRAF inhibitor on melanoma xenograft in mice: evaluation of 18F‐FDG‐PET and 18F‐FLT‐PET
Authors: Geven Edwin J. W. , Evers Stefan , Nayak Tapan K. , Bergström Mats , Su Fei , Gerrits Danny , Franssen Gerben M. , Boerman Otto C.
Published: September 2014

Inhibition of the V600E mutated BRAF kinase gene (BRAFV600E) is an important and effective approach to treating melanomas. A new specific small molecule inhibitor of BRAFV600E, PLX3603, showed potent melanoma growth‐inhibiting characteristics in preclinical studies and is currently under clinical investigation. In this study we investigated the feasibility of 18F‐FDG and 18F‐FLT‐PET to monitor the early effects of the BRAFV600E inhibitor in mice with melanoma xenografts. SCID/beige mice with subcutaneous (s.c.) A375 melanoma xenografts, expressing BRAFV600E, received the BRAFV600E inhibitor twice daily orally (0, 25, 50 and 75 mg/kg). At 1, 3 and 7 days after start of therapy, the uptake of 18F‐FDG and 18F‐FLT in the tumor and normal tissues was determined in ex vivo tissue samples. Serial 18F‐FDG and 18F‐FLT‐PET scans were acquired of animals at 1 day before and 1, 3 and 7 days after start of treatment with 75 mg/kg BRAFV600E inhibitor. A dose‐dependent decrease in 18F‐FDG uptake in the A375 tumors was observed by ex vivo biodistribution analysis. Administration of 75 mg/kg BRAF inhibitor for 1, 3 and 7 days resulted in a significantly decreased 18F‐FDG uptake in A375 tumors (41, 35 and 51%, respectively). 18F‐FLT uptake in the A375 tumors was low at baseline and no significant changes in 18F‐FLT uptake were observed at any of the doses administered. These effects were corroborated by serial in vivo 18F‐FDG and 18F‐FLT‐PET imaging. These data demonstrate that 18F‐FDG‐PET can be used as an imaging biomarker to noninvasively evaluate the early effects of PLX3603. Copyright © 2014 John Wiley & Sons, Ltd.
Multimodal imaging for improved diagnosis and treatment of cancers
Authors: Tempany Clare M. C. , Jayender Jagadeesan , Kapur Tina , Bueno Raphael , Golby Alexandra , Agar Nathalie , Jolesz Ferenc A.
Published: September 2014

The authors review methods for image‐guided diagnosis and therapy that increase precision in the detection, characterization, and localization of many forms of cancer to achieve optimal target definition and complete resection or ablation. A new model of translational, clinical, image‐guided therapy research is presented, and the Advanced Multimodality Image‐Guided Operating (AMIGO) suite is described. AMIGO was conceived and designed to allow for the full integration of imaging in cancer diagnosis and treatment. Examples are drawn from over 500 procedures performed on brain, neck, spine, thorax (breast, lung), and pelvis (prostate and gynecologic) areas and are used to describe how they address some of the many challenges of treating brain, prostate, and lung tumors. Cancer 2015;121:817–827. © 2014 American Cancer Society.
Interactive Chemical Reactivity Exploration
Authors: Haag Moritz P. , Vaucher Alain C. , Bosson Maël , Redon Stéphane , Reiher Markus
Published: September 2014

Elucidating chemical reactivity in complex molecular assemblies of a few hundred atoms is, despite the remarkable progress in quantum chemistry, still a major challenge. Black‐box search methods to find intermediates and transition‐state structures might fail in such situations because of the high‐dimensionality of the potential energy surface. Here, we propose the concept of interactive chemical reactivity exploration to effectively introduce the chemist’s intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mechanical response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which technical difficulties need to be overcome. All reactivity‐exploration concepts developed for this purpose have been implemented in the samson programming environment.
Silicon Nanowire Photocathodes for Light‐Driven Electroenzymatic Synthesis
Authors: Lee Sahng Ha , Ryu Gyeong Min , Nam Dong Heon , Kim Jae Hong , Park Chan Beum
Published: September 2014

The photoelectroenzymatic synthesis of chemical compounds employing platinum nanoparticle‐decorated silicon nanowires (Pt‐SiNWs) is presented. The Pt‐SiNWs proved to be an efficient material for photoelectrochemical cofactor regeneration because the silicon nanowires absorbs a wide range of the solar spectrum while the platinum nanoparticle serve as an excellent catalyst for electron and proton transfer. By integrating the platform with redox enzymatic reaction, visible‐light‐driven electroenzymatic synthesis of L‐glutamate was achieved. Compared to electrochemical and photochemical methods, this approach is free from side reactions caused by sacrificial electron donors and has the advantage of applying low potential to realize energy‐efficient and sustainable synthesis of chemicals by a photoelectroenzymatic system.
Operando and In situ X‐ray Spectroscopies of Degradation in La0.6Sr0.4Co0.2Fe0.8O3−δ Thin Film Cathodes in Fuel Cells
Authors: Lai Samson Y. , Ding Dong , Liu Mingfei , Liu Meilin , Alamgir Faisal M.
Published: September 2014

Information from ex situ characterization can fall short in describing complex materials systems simultaneously exposed to multiple external stimuli. Operando X‐ray absorption spectroscopy (XAS) was used to probe the local atomistic and electronic structure of specific elements in a La0.6Sr0.4Co0.2Fe0.8O3−δ (LSCF) thin film cathode exposed to air contaminated with H2O and CO2 under operating conditions. While impedance spectroscopy showed that the polarization resistance of the LSCF cathode increased upon exposure to both contaminants at 750 °C, XAS near‐edge and extended fine structure showed that the degree of oxidation for Fe and Co decreases with increasing temperature. Synchrotron‐based X‐ray photoelectron spectroscopy tracked the formation and removal of a carbonate species, a Co phase, and different oxygen moieties as functions of temperature and gas. The combined information provides insight into the fundamental mechanism by which H2O and CO2 cause degradation in the cathode of solid oxide fuel cells.
Trade‐offs in seedling growth and survival within and across tropical forest microhabitats
Authors: Inman‐Narahari Faith , Ostertag Rebecca , Asner Gregory P. , Cordell Susan , Hubbell Stephen P. , Sack Lawren
Published: September 2014

For niche differences to maintain coexistence of sympatric species, each species must grow and/or survive better than each of the others in at least one set of conditions (i.e., performance trade‐offs). However, the extent of niche differentiation in tropical forests remains highly debated. We present the first test of performance trade‐offs for wild seedlings in a tropical forest. We measured seedling relative growth rate (RGR) and survival of four common native woody species across 18 light, substrate, and topography microhabitats over 2.5 years within Hawaiian montane wet forest, an ideal location due to its low species diversity and strong species habitat associations. All six species pairs exhibited significant performance trade‐offs across microhabitats and for RGR versus survival within microhabitats. We also found some evidence of performance equivalence, with species pairs having similar performance in 26% of comparisons across microhabitats. Across species, survival under low light was generally positively associated with RGR under high light. When averaged over all species, topography (slope, aspect, and elevation) explained most of the variation in RGR attributable to microhabitat variables (51–53%) followed by substrate type (35–37%) and light (11–12%). However, the relative effects of microhabitat differed among species and RGR metric (i.e., RGR for height, biomass, or leaf area). These findings indicate that performance trade‐offs among species during regeneration are common in low‐diversity tropical forest, although other mechanisms may better explain the coexistence of species with small performance differences.
Matrix liposomes: A solid liposomal formulation for oral administration
Authors: Pantze Silvia F. , Parmentier Johannes , Hofhaus Götz , Fricker Gert
Published: September 2014

Liposomes can be used as oral dosage form to improve the bioavailability of both hydrophilic drugs, such as peptides and proteins and lipophilic drugs. But liposome dispersions are not very stable under the harsh conditions of the GI‐tract. Also a controlled release of embedded compounds is not possible. Therefore we developed a lipid based liposomal carrier system for peroral delivery of peptides. The lipid bilayer of standard egg‐PC/cholesterol liposomes were stabilized by gelatine. The gelatine also works as a thickening agent by forming a matrix in which liposomes are embedded. Liposomes were prepared by dual asymmetric centrifugation with the addition of gelatine. Size and size distribution of prepared liposomes with up to 20% gelatine achieved the same quality compared to conventional liposomes. Size and size distribution, encapsulation efficiency of different compounds and the dissolution behaviour of the solid dosage form in simulated intestinal fluid were examined. Matrix liposomes containing 20% gelatine showed an approximately linear release of liposomes. Moreover, the dissolution rate could be adjusted by modification of the gelatine concentration and the absolute amount of liposomes released at a certain time was found to be dose dependent.

Practical applications: The new liposomal solid formulation can be useful for a controlled release of hydrophilic macromolecules as peptides and proteins after peroral administration. Liposomes embedded in a solid dosage form offer the possibility of a simple administration and exhibit higher storage stability compared to liposomes in dispersion.

A composition of phospholidpids and gelatine leads to matrix liposomes prepared by dual asymmetric centrifugation. Dissolution of the solid liposomal formulation leads to a liposome release out of the dosage form. The dissolution rate can be adjusted by the concentration of gelatine.
Formation of a Zwitterionic Enolate from Tetramethylthiourea and Dimethyl Acetylenedicarboxylate
Authors: Wannebroucq Amélie , Pitak Mateusz B. , Coles Simon J. , Wallis John D.
Published: September 2014

A zwitterionic tetrahydrothiophen‐3‐one derivative containing the enolate of a β‐keto ester located in the ring and a tetramethylamidinium group in a side chain is formed from tetramethylthiourea and dimethyl acetylenedicarboxylate by a surprising rearrangement reaction. Low‐temperature X‐ray crystallography shows weak intramolecular coordination of an enolate O atom by the amidinium group (O···C: 2.608 Å) and also a 1,5 S···O short contact (2.706 Å) due to electron delocalisation in a cis‐sulfanylacrylate grouping.
A Convergent Synthesis of Carbocyclic Sinefungin and its C‐5 Epimer
Authors: Ghosh Arun K. , Lv Kai
Published: September 2014

A convergent synthesis of carbocyclic sinefungin (2), its C‐5 epimer 3a, and adenine‐modified derivative 3b is described. The key features of our approach include the use of commercially available L‐methionine and readily available (1R,4S)‐4‐hydroxy‐2‐cyclopentenyl acetate as starting materials, a cross‐metathesis reaction, an enzymatic kinetic resolution, and a Staudinger reduction. The current synthesis is flexible and, therefore, provides convenient access to the synthesis of various carbocyclic sinefungin analogues for biological evaluation.
The Nazarov Cyclization: A Valuable Method to Synthesize Fully Substituted Carbon Stereocenters
Authors: Wenz Donald R. , Read de Alaniz Javier
Published: September 2014

The synthesis of fully substituted carbon stereocenters remains a challenging task in organic chemistry. Recent developments in the design of substrates that undergo the Nazarov cyclization have enabled this reaction to become a valuable way to form elaborately substituted cyclopentane rings containing fully substituted carbon stereocenters. Three major strategies have been utilized in this endeavor. Here we provide an overview of these three areas that should give insight into the usage of the Nazarov reaction for the challenging task of forming fully substituted carbon stereocenters.
One‐Pot Preparation of Chiral Carbacycles from Morita–Baylis–Hillman Carbonates by an Asymmetric Allylic Alkylation/Olefin Metathesis Sequence
Authors: Putaj Piotr , Tichá Iveta , Císařová Ivana , Veselý Jan
Published: September 2014

An operationally simple, one‐pot synthetic protocol for the formation of all‐carbon, highly substituted five‐ and six‐membered rings is described. In this two‐step procedure, an asymmetric allylic alkylation (AAA) of Morita–Baylis–Hillman (MBH) carbonates with allylmalononitrile, catalyzed by a chiral tertiary amine, is followed by a ring‐closing alkene metathesis (RCM) reaction. Products are obtained in high yields, and an excellent level of optical purity of some of the target compounds is achieved after just a single recrystallization.
Application of Polyfolates in the Development of Electrochemical Glucose Biosensors
Authors: Venckus Tautvydas , Celiešiūtė Raimonda , Radzevič Aneta , Rakickas Tomas , Vaitekonis Šarūnas , Ruželė Živilė , Pauliukaite Rasa
Published: September 2014

Folic acid was polymerised electrochemically at a glassy carbon electrode surface from 0.1 mol L−1 phosphate buffer saline solution, pH 5.0, containing 0.1 mmol L−1 monomer. The obtained thin film was porous with a pore size of 50–60 nm. Since its electrochemical stability was rather short, the polyfolate film was covered with a graphene‐chitosan composite layer which increased its stability significantly. The best strategy to immobilise the enzyme was crosslinking with glutaraldehyde. The lifetime of this glucose biosensor in use was at least 12 days, on‐shelf life time was at least 30 days. The linear range was up to 1 mmol L−1 and the LOD was 0.6 µmol L−1. The first polyfolate‐based biosensor was applied to analysis of natural samples.
Community mental health teams for older people: variations in case mix and service receipt (II)
Authors: Wilberforce Mark , Tucker Sue , Brand Christian , Abendstern Michele , Jasper Rowan , Stewart Karen , Challis David
Published: September 2014

Objectives

To determine the extent to which services provided to older people via community mental health teams (CMHTs) vary in duration, composition and intensity. In particular, to identify the degree to which differences between teams are due to casemix.

Methods

Data were collected about the services provided to a random sample of patients from 15 CMHT caseloads, including contact with CMHT staff, other specialist mental health and social care services. The relationship between patients' needs and service receipt was explored.

Results

Information was obtained for 1396 patients. Average time on CMHT caseloads was 11.6 months, but there were marked between‐team differences. The proportion of re‐referrals also varied from under a tenth to over half. People with functional mental health problems and complex needs were most likely to be long‐term CMHT clients. The proportion of patients seen by a consultant in the previous 6 months ranged from approximately a fifth to almost all. Differences with respect to contact with other qualified practitioners were less marked. Older people with functional disorders, challenging behaviour and at least one medium risk had the most regular contact with CMHT staff. Risk of self‐harm, delusions and paranoia increased the likelihood of consultant involvement. Support workers were more likely to see people at risk of self‐neglect. The receipt of other services, including day hospitals and inpatient care varied greatly.

Conclusions

Considerable diversity was found in the length, nature and frequency of services provided to patients with different needs. Differences between teams were not wholly explained by case mix. Copyright © 2014 John Wiley & Sons, Ltd.
ALCAT1 controls mitochondrial etiology of fatty liver diseases, linking defective mitophagy to steatosis
Authors: Wang Li , Liu Xiaolei , Nie Jia , Zhang Jun , Kimball Scot R. , Zhang Hai , Zhang Weiping J. , Jefferson Leonard S. , Cheng Zeneng , Ji Qiuhe , Shi Yuguang
Published: September 2014

Defective autophagy is implicated in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD) through poorly defined mechanisms. Cardiolipin is a mitochondrial phospholipid required for bioenergetics and mitophagy from yeast to mammals. Here we investigated a role for ALCAT1 in the development of NAFLD. ALCAT1 is a lysocardiolipin acyltransferase that catalyzes pathological cardiolipin remodeling in several aging‐related diseases. We show that the onset of diet‐induced NAFLD caused autophagic arrest in hepatocytes, leading to oxidative stress, mitochondrial dysfunction, and insulin resistance. In contrast, targeted deletion of ALCAT1 in mice prevented the onset of NAFLD. ALCAT1 deficiency also restored mitophagy, mitochondrial architecture, mitochondrial DNA (mtDNA) fidelity, and oxidative phosphorylation. In support of a causative role of the enzyme in a mitochondrial etiology of the disease, hepatic ALCAT1 expression was significantly up‐regulated in mouse models of NAFLD. Conclusion: Forced expression of ALCAT1 in primary hepatocytes led to multiple defects that are highly reminiscent of NAFLD, including steatosis, defective autophagy, and mitochondrial dysfunction, linking pathological cardiolipin remodeling by ALCAT1 to the pathogenesis of NAFLD. (Hepatology 2015;61:486‐496)
Predictors of poor mental and physical health status among patients with chronic hepatitis C infection: The Chronic Hepatitis Cohort Study (CHeCS)
Authors: Boscarino Joseph A. , Lu Mei , Moorman Anne C. , Gordon Stuart C. , Rupp Loralee B. , Spradling Philip R. , Teshale Eyasu H. , Schmidt Mark A. , Vijayadeva Vinutha , Holmberg Scott D. ,   for the Chronic Hepatitis Cohort Study (CHeCS) Investigators
Published: September 2014

Our objective was to assess the extent and risk factors for depression and poor physical health among patients with chronic hepatitis C virus (HCV) infection. We surveyed HCV‐infected patients seen at four large healthcare systems participating in the Chronic Hepatitis Cohort Study (CHeCS). Survey data included demographics, depression and physical health measures, substance use history, current social support, recent stressor exposures, and, from the electronic medical record, treatment history, and Charlson Comorbidity Index scores. There were 4,781 respondents, who were a mean of 56.7 years old, 71% White, and 57% male. Altogether, 51.4% reported past injection drug use, 33.9% were current smokers, and 17.7% had abused alcohol in the previous year. Additionally, 47.4% had been previously treated for HCV and 14.8% had a 12‐week sustained viral response (SVR) following HCV therapy. Overall, 29.7% of patients met criteria for current depression and 24.6% were in poor physical health. In multivariate analyses, significant predictors of depression and poor health included: male gender (versus female, odds ratios [ORs], 0.70 and 0.81), Black race (versus white, ORs, 0.60 and 0.61), having education less than high school (versus college, ORs, 1.81 and 1.54), being employed (versus not, ORs, 0.36 and 0.25), having high life stressors (versus low, ORs, 2.44 and 1.64), having low social support (versus high, ORs = 2.78 and 1.40), and having high Charlson scores (versus none, ORs = 1.58 and 2.12). Achieving a 12‐week SVR was found to be protective for depression. Conclusion: This large survey of U.S. HCV patients indicates the extent of adverse health behaviors and mental and physical comorbidities among these patients. (Hepatology 2015;61:802–811)
Multi‐site calibration using a grid‐based event rainfall–runoff model: a case study of the upstream areas of the Nakdong River basin in Korea
Authors: Choi Yun Seok , Choi Cheon Kyu , Kim Hung Soo , Kim Kyung Tak , Kim Soojun
Published: September 2014

Most runoff analyses using a grid‐based distributed model use one parameter group calibrated at the outlet of a watershed, instead of dividing the watershed into subwatersheds. Significant differences between the observed value and the simulation result of the subwatersheds can occur if just one parameter group is used in all subwatersheds that have different hydrological characteristics from each other. Therefore, to improve the simulation results of the subwatersheds within a watershed, a model calibrated at every subwatershed needs to be used to reflect the characteristics of each subwatershed. In this study, different parameter groups were set up for one or two sites using a distributed model, the GRM (Grid based Rainfall‐runoff Model), and the evaluations were based on the results of rainfall–runoff analysis, which uses a multi‐site calibration (MSC) technique to calibrate the model at the outlet of each site. The Hyangseok watershed in Naeseong River, which is a tributary of Nakdong River in Korea, was chosen as the study area. The watershed was divided into five subwatersheds each with a subwatershed outlet that was applied to the calibration sites. The MSC was applied for five cases. When a site was added for calibration in a watershed, the runoff simulation showed better results than the calibration of only one site at the most downstream area of the watershed. The MSC approach could improve the simulation results on the calibrated sites and even on the non‐calibrated sites, and the effect of MSC was improved when the calibrated site was closer to the runoff site. Copyright © 2014 John Wiley & Sons, Ltd.
Quantifying evaporation in a permeable pavement system
Authors: Brown Robert A. , Borst Michael
Published: September 2014

Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger field application by measuring the water balance from lined permeable pavement sections. The U.S. Environmental Protection Agency constructed a 0.4 ha parking lot in Edison, NJ, that incorporated three different permeable pavement types in the parking lanes – permeable interlocking concrete pavers (PICP), pervious concrete (PC) and porous asphalt (PA). An impermeable liner installed 0.4 m below the surface in four 11.6 m by 4.74 m sections per each pavement type captures all infiltrating water and routes it to collection tanks that can contain events up to 38 mm. Each section has a design impervious area to permeable pavement area ratio of 0.66:1. Pressure transducers installed in the underdrain collection tanks measured water level for 24 months. Level was converted to volume using depth‐to‐volume ratios for individual collection tanks. Using a water balance approach, the measured infiltrate volume was compared to rainfall volume on an event basis to determine the rainfall retained in the pavement strata and underlying aggregate. Interevent evaporation created additional storage in the pavement and aggregate layers. Events were divided into three groups based on antecedent dry period (ADP) and three 4 month groups of potential evaporation based on historical monthly pan evaporation records. There was a significant difference in rainfall retained among the various combinations of ADP and potential evaporation groups. More rainfall was retained in the pavement and aggregate layers as time between events increased and during warmer months with larger potential evaporation. Average cumulative evaporation from the permeable pavement sections for 134 rainfall events in 24 months was 5.2% of the cumulative rainfall volume, and the range was 2.4–7.6%. Each PC section had more annual evaporation than any individual PICP or PA section. While measureable, evaporation is a small contribution to the total water budget on an annual basis for these systems. Copyright © 2014 John Wiley & Sons, Ltd.
Drug Cross‐Contamination of Barcode Unit Dose Repackager in a Tertiary Academic Medical Centre
Authors: Huat Tan Chwee , Hong Goh Lay , Seng Wu Tuck
Published: September 2014

Background

National University Hospital and Tan Tock Seng Hospital have implemented an automated barcoded unit dose repackaging machine to provide barcoded medications for bedside verification to ensure the right medication is administered to the right patient. Because the machine stores and repackages multiple medications concurrently, there could be a risk of drug cross‐contamination.

Aim

To validate the vendor‐recommended cleaning procedures and to establish whether there was any cross‐contamination of drugs using selected test medications.

Method

Eight medications were selected to be the test medications with representative attributes. Paracetamol 500 mg tablets were selected as the carrier medication. First, to validate cleaning procedures, test medications were repackaged, followed by routine cleaning of the machine before the paracetamol tablets were repackaged. Second, to investigate the risk of drug cross‐contamination, test medications were repackaged, followed by repackaging of paracetamol tablets. The paracetamol tablets were then tested for drug cross‐contamination from the test medications using HPLC analysis to detect and/or quantify the presence of contamination. The maximum allowable limit of each test medication detected on a total of eight paracetamol tablets was set as no more than 0.1% of the minimum therapeutic dose.

Results

All paracetamol tablet samples tested had detectable concentrations of test medications that were below the maximum allowable limits for the eight tested medications.

Conclusion

It was established that: (1) the routine cleaning procedures recommended by the vendor are appropriate; and (2) there was no clinically significant drug cross‐contamination during repackaging of the selected eight test medications.
Does an Electronic Discharge Referral System Improve the Quality of Medication Prescribing?
Authors: Garrett Tim , McCormack Claire
Published: September 2014

Background

Unintentional discrepancies in medication lists at the time of discharge are common and a significant cause of avoidable harm. Electronic discharge referral (eDR) systems represent an opportunity to reduce the risk of harm. However, there are few Australian studies describing this approach.

Aim

To investigate the impact of an eDR system on the quality of medication prescribing.

Method

A prospective, observational study of discharge medication orders was undertaken in a 520‐bed principal referral hospital. A structured audit tool was used to assess the quality (volume, type and severity) of prescribing errors on patients' discharge summaries for 2 weeks immediately before the implementation of the eDR system (pre‐eDR) and re‐audited 6 weeks after implementation (post‐eDR).

Results

Discharge summaries from 776 patients were evaluated (n = 377 pre‐eDR (handwritten process); n = 399 post‐eDR (electronic process)). The number of discharges with one or more prescribing errors decreased significantly after implementation of the eDR system (relative difference −39.6%; P < 0.001), including errors relating to: supply quantities (P < 0.001), legibility (P < 0.0001), drug selection (P = 0.009), prescription format selection (P = 0.026), patient details (P = 0.039) and signing of orders (P = 0.007). However, no significant difference was observed in the overall mean severity score for errors between the electronic and handwritten discharge processes (3.5 vs 3.4; P = 0.28).

Conclusion

Implementation of an eDR system resulted in an improved quality and potential safety of patients' discharge medication orders. However, despite a reduced frequency of errors, the emergence of new error types was observed, and the profile and overall severity of prescribing errors remained unchanged.
Optimising Therapy for Patients with Neuropathic Pain
Authors: Westaway Kerrie P , Alderman Christopher P , Frank Oliver R , Husband Alan J , Rowett Debra , Le Blanc Tammy
Published: September 2014

Neuropathic pain is a common condition that affects people of all ages, but is especially prevalent among older people because the incidence of many diseases that cause neuropathic pain increases with age. Neuropathic pain is often underdiagnosed or undertreated, and is associated with a diminished quality of life, significant disability and depression. The principal aim of management is to improve the patient's quality of life by attaining maximum pain relief with minimal treatment‐associated adverse effects, and restoring functional ability. The current therapeutic options for the management of neuropathic pain are reviewed here, focusing on the importance of an accurate diagnosis and assessment, early intervention, regular clinical reviews and steps in pharmacological treatment.
In vivo study of nanostructured akermanite/PEO coating on biodegradable magnesium alloy for biomedical applications
Authors: Razavi Mehdi , Fathi Mohammadhossein , Savabi Omid , Vashaee Daryoosh , Tayebi Lobat
Published: September 2014

The major issue for biodegradable magnesium alloys is the fast degradation and release of hydrogen gas. In this article, we aim to overcome these disadvantages by using a surface modified magnesium implant. We have recently coated AZ91 magnesium implants by akermanite (Ca2MgSi2O7) through the combined electrophoretic deposition (EPD) and plasma electrolytic oxidation (PEO) methods. In this work, we performed the in vitro and in vivo examinations of these coated implants using L‐929 cell line and rabbit animal model. The in vitro study confirmed the higher cytocompatibility of the coated implants compare to the uncoated ones. For the in vivo experiment, the rod samples were implanted into the greater trochanter of rabbits and monitored for two months. The results indicated a noticeable biocompatibility improvement of the coated implants which includes slower implant weight loss, reduction in Mg ion released from the coated samples in the blood plasma, lower release of hydrogen bubbles, increase in the amount of bone formation and ultimately lower bone inflammation after the surgery according to the histological images. Our data exemplifies that the proper surface treatment of the magnesium implants can improve their biocompatibility under physiological conditions to make them applicable in clinical uses. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1798–1808, 2015.
Controlled surface morphology and hydrophilicity ofpolycaprolactonetoward selective differentiation of mesenchymal stem cells to neural like cells
Authors: Jahani Hoda , Jalilian Farid Azizi , Wu Chia‐Yu , Kaviani Saeid , Soleimani Masoud , Abbasi Naghmeh , Ou Keng‐Liang , Hosseinkhani Hossein
Published: September 2014

Differentiation of mesenchymal stem cells (MSCs) into neuron cells has great potential in therapy of damaged nerve tissue. It has been shown that three‐dimensional biomaterials have great ability to up regulate the expression of neuronal proteins. In this study, O2plasma technology was used to enhance hydrophilicity of poly (ε‐caprolactone) (PCL) toward selective differentiation of MSCs into neural cells. Random and aligned PCL nanofibers scaffolds were fabricated by electrospinning method and their physicochemical and mechanical properties were carried out by scanning electron microscope (SEM), contact angle, and tensile measurements. Contact angle studies of PCL and plasma treated PCL (p‐PCL) nanofibers revealed significant change on the surface properties PCL nanofibers from the view point of hydrophilicity. Physiochemical studies revealed thatp‐PCL nanofibers were extremely hydrophilic compared with untreated PCL nanofibers which were highly hydrophobic and nonabsorbent to water. Differentiation of MSCs were carried out by inducing growth factors including basic fibroblast growth factor, nerve growth factor, and brain derived growth factor, NT3, 3‐isobutyl‐1‐methylxanthine (IBMX) in Dulbecco's modified Eagle's medium/F12 media. Differentiated MSCs on nanofibrous scaffold were examined by immunofluorescence assay and was found to express the neuronal proteins; β‐tubulin III and Map2, on day 15 after cell culture. The real‐time polymerase chain reaction (RT‐PCR) analysis showed thatp‐PCL nanofibrous scaffold could upregulate expression of Map‐2 and downregulate expression of Nestin genes in nerve cells differentiated from MSCs. This study indicates that mesenchymal stem cell cultured on nanofibrous scaffold have potential differentiation to neuronal cells on and could apply in nerve tissue repair. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1875–1881, 2015.
Focal Adhesion Kinase Knockdown in Carcinoma‐Associated Fibroblasts Inhibits Oral Squamous Cell Carcinoma Metastasis via Downregulating MCP‐1/CCL2 Expression
Authors: Min Anjie , Zhu Chao , Wang Jingyi , Peng Shuping , Shuai Cijun , Gao Shan , Tang Zhangui , Su Tong
Published: September 2014

Carcinoma‐associated fibroblasts (CAFs) have been demonstrated to play an important role in the occurrence and development of oral squamous cell carcinoma (OSCC). The aim of this study is to investigate the influence of CAFs on OSCC cells and to explore the role of focal adhesion kinase (FAK) in this process. The results showed that oral CAFs expressed a higher level of FAK than normal human gingival fibroblasts (HGFs), and the conditioned medium (CM) of CAFs could induce the invasion and migration of SCC‐25, one oral squamous carcinoma cell line. However, knockdown of FAK by small interfering RNA (siRNA) resulted in inhibition of CAF–CM induced cell invasion and migration in SCC‐25, probably by reducing the production of monocyte chemoattractant protein‐1 (MCP‐1/CCL2), one of downstream target chemokines. Therefore, our findings indicated that targeting FAK in CAFs might be a promising strategy for the treatment of OSCC in the future.
Application of the Stabilized Koopmans’ Theorem to the Temporary Anion States of Chlorosilanes in Long‐Range Corrected Density Functional Theory
Authors: Cheng Hsiu‐Yao , Huang Yu‐Shiuan , Huang Pin‐Qi
Published: September 2014

The stabilized Koopmans’ theorem (SKT) is very successful in predicting relative vertical electron attachment energies in the Hartree‐Fock theory. It is mainly accomplished by systematically scaling the most diffuse functions in the basis set. Recently, the SKT has been extended to the temporary anion states (TASs) of polyatomic molecules in the long‐range corrected density functional theory. In this paper, this method will be further applied to chlorosilanes for their importance in the chemical processes of the semiconductor industry. Their resonance energies and lifetimes are determined by computing the density of resonance states via SKT. The detailed characteristics of resonance orbitals are then analyzed. It turns out that the lowest unfilled orbitals of chlorosilanes are essentially σ*Si‐Cl in character. Moreover, several TASs with strong Si/Cl “d” character have been identified. These results, definitely, will help us in understanding the peculiar bonding and chemical properties of chlorosilanes.
IR, Raman, and Surface‐enhanced Raman Spectroscopic Study on Triruthenium Dipyridylamide Diruthenium Nickel Dipyridylamide Family: Metal‐metal Bonding and Structures
Authors: Chiu Yu‐Chun , Ho Kuan‐Yi , Chen a I‐Chia , Hua Shao‐An , Cheng Ming‐Chuan , Peng Shie‐Ming
Published: September 2014

We report the infrared, Raman, and surface‐enhanced Raman scattering (SERS) spectra of triruthenium dipyridylamido complexes and of diruthenium mixed nickel metal‐string complexes. From the results of analysis on the vibrational modes, we assigned their vibrational frequencies and structures. The infrared band at 323–326 cm−1 is assigned to the Ru3 asymmetric stretching mode for [Ru3(dpa)4Cl2]0–2+. In these complexes we observed no Raman band corresponding to the Ru3 symmetric stretching mode although this mode is expected to have substantial Raman intensity. There is no frequency shift in the Ru3 asymmetric stretching modes for the complexes with varied oxidational states. No splitting in Raman spectra for the pyridyl breathing line indicates similar bonding environment for both pyridyls in dpa– , thus a delocalized structure in the [Ru3]6–8+ unit is proposed. For Ru3(dpa)4(CN)2 complex series, we assign the infrared band at 302 cm−1 to the Ru3 asymmetric stretching mode and the weak Raman line at 285 cm−1 to the Ru3 symmetric stretching. Coordination to the strong axial ligand CN– weakens the Ru‐Ru bonding. For the diruthenium nickel complex [Ru2Ni(dpa)4Cl2]0–1+, the diruthenium stretching mode νRu‐Ru is assigned to the intense band at 327 and 333 cm−1 in the Raman spectra for the neutral and oxidized forms, respectively. This implies a strong Ru‐Ru metal‐metal bonding.
Some New Infinite Classes of Candelabra Quadruple Systems
Authors: Zhang Shaopu , Ji Lijun , Song Guojie
Published: September 2014

Candelabra quadruple systems (CQS) were first introduced by Hanani who used them to determine the existence of Steiner quadruple systems. In this paper, a new method has been developed by constructing partial candelabra quadruple systems with odd group size, which is a generalization of the even cases, to complete a design. New results of candelabra quadruple systems have been obtained, i.e. we show that for any , there exists a CQS for all , and .
MSCs Modified With ACE2 Restore Endothelial Function Following LPS Challenge by Inhibiting the Activation of RAS
Authors: He Hong‐li , Liu Ling , Chen Qi‐hong , Cai Shi‐xia , Han Ji‐bin , Hu Shu‐ling , Chun Pan , Yang Yi , Guo Feng‐mei , Huang Ying‐zi , Qiu Hai‐bo
Published: September 2014

Angiotensin (Ang) II plays an important role in the process of endothelial dysfunction in acute lung injury (ALI) and is degraded by angiotensin‐converting enzyme2 (ACE2). However, treatments that target ACE2 to injured endothelium and promote endothelial repair of ALI are lacking. Mesenchymal stem cells (MSCs) are capable of homing to the injured site and delivering a protective gene. Our study aimed to evaluate the effects of genetically modified MSCs, which overexpress the ACE2 protein in a sustained manner via a lentiviral vector, on Ang II production in endothelium and in vitro repair of lipopolysaccharide (LPS)‐induced endothelial injury. We found that the efficiency of lentiviral vector transduction of MSCs was as high as 97.8% and was well maintained over 30 passages. MSCs modified with ACE2 showed a sustained high expression of ACE2 mRNA and protein. The modified MSCs secreted soluble ACE2 protein into the culture medium, which reduced the concentration of Ang II and increased the production of Ang 1–7. MSCs modified with ACE2 were more effective at restoring endothelial function than were unmodified MSCs, as shown by the enhanced survival of endothelial cells; the downregulated production of inflammatory mediators, including ICAM‐1, VCAM‐1, TNF‐α, and IL‐6; reduced paracellular permeability; and increased expression of VE‐cadherin. These data demonstrate that MSCs modified to overexpress the ACE2 gene can produce biologically active ACE2 protein over a sustained period of time and have an enhanced ability to promote endothelial repair after LPS challenge. These results encourage further testing of the beneficial effects of ACE2‐modified MSCs in an ALI animal model. J. Cell. Physiol. 230: 691–701, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Palmitate‐Stimulated Monocytes Induce Adhesion Molecule Expression in Endothelial Cells via IL‐1 Signaling Pathway
Authors: Shikama Yosuke , Aki Nanako , Hata Akiko , Nishimura Miho , Oyadomari Seiichi , Funaki Makoto
Published: September 2014

Increased intake of saturated fatty acids (SFAs), such as palmitate (Pal), is linked to a higher risk of type 2 diabetes and cardiovascular disease. Although recent studies have investigated the direct effects of SFAs on inflammatory responses in vascular endothelial cells, it remains unknown whether SFAs also induce these responses mediated by circulating cells. In this study, especially focused on adhesion molecules and monocytes, we investigated the indirect effects of Pal on expression and release of ICAM‐1 and E‐selectin in vascular endothelial cells. Phorbol 12‐myristate 13‐acetate (PMA)‐treated THP‐1 (pTHP‐1) cells and human monocytes were stimulated with various free fatty acids (FFAs). SFAs, but not unsaturated fatty acids (UFAs), increased interleukin (IL)‐1β secretion and decreased IL‐1 receptor antagonist (IL‐1Ra) secretion, resulting in an increase in the IL‐1β/IL‐1Ra secretion ratio. UFAs dose‐dependently inhibited the increase in IL‐1β secretion and decrease in IL‐1Ra secretion induced by Pal. Moreover, in human aortic and vein endothelial cells, expression and release of ICAM‐1 and E‐selectin were induced by treatment with conditioned medium collected from Pal‐stimulated pTHP‐1 cells and human monocytes, but not by Pal itself. The up‐regulated expression and release of adhesion molecules by the conditioned medium were mostly abolished by recombinant human IL‐1Ra supplementation. These results suggest that the Pal‐induced increase in the ratio of IL‐1β/IL‐1Ra secretion in monocytes up‐regulates endothelial adhesion molecules, which could enhance leukocyte adhesion to endothelium. This study provides further evidence that IL‐1β neutralization through receptor antagonism may be useful for preventing the onset and development of cardiovascular disease. J. Cell. Physiol. 230: 732–742, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Acetylcholine Inhibits Tumor Necrosis Factor α Activated Endoplasmic Reticulum Apoptotic Pathway via EGFR‐PI3K Signaling in Cardiomyocytes
Authors: Miao Yi , Bi Xue‐Yuan , Zhao Mei , Jiang Hong‐Ke , Liu Jin‐Jun , Li Dong‐Ling , Yu Xiao‐Jiang , Yang Yong‐Hua , Huang Ning , Zang Wei‐Jin
Published: September 2014

Previous findings have shown that acetylcholine (ACh) decreased hypoxia‐induced tumor necrosis factor alpha (TNF α) production, thus protected against cardiomyocyte injury. However, whether and how ACh affects TNF α‐induced endoplasmic reticulum (ER) stress and cell apoptosis remain poorly defined. This study was aimed at determining the effect of ACh in H9c2 cells after TNF α stimulation. Presence of ER stress was verified using the ER stress protein markers glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP). Cell apoptosis was shown by caspase‐3 activation and terminal deoxynucleotidyl transferase mediated dUTP‐biotin nick end labeling. Exogenously administered ACh significantly decreased these TNF α‐induced changes. Moreover, when the cells were exposed to nonspecific muscarinic receptor (M AChR) inhibitor atropine, methoctramine (M2 AChR inhibitor) or the epidermal growth factor receptor (EGFR) inhibitor AG1478, the cardioprotection elicited by ACh was diminished. Furthermore, the above effects were also blocked by M2 AChR or EGFR siRNA, indicating that EGFR transactivation by M2 AChR may be the major pathway responsible for the benefits of ACh. In addition, LY294002, a phosphatidylinositol‐3‐kinase (PI3K) inhibitor, displayed the similar trends as AG1478, suggesting that PI3K/Akt signaling may be the downstream of EGFR in ACh‐elicited anti‐apoptotic property. Together, these data indicate that EGFR‐PI3K/Akt signaling is involved in M2 AChR‐mediated ER apoptotic pathway suppression and the subsequent survival of H9c2 cardiomyocytes. We have identified a novel pathway underlying the cardioprotection afforded by ACh. J. Cell. Physiol. 230: 767–774, 2015. © 2014 Wiley Periodicals, Inc.
Role of Acinus in Regulating Retinoic Acid‐Responsive Gene Pre‐mRNA Splicing
Authors: Wang Fang , Soprano Kenneth J. , Soprano Dianne Robert
Published: September 2014

Acinus‐S’ is a corepressor for retinoic acid receptor (RAR)‐dependent gene transcription and has been suggested to be involved in RNA processing. In this study, the role of Acinus isoforms in regulating pre‐mRNA splicing was explored using in vivo splicing assays. Both Acinus‐L and Acinus‐S’, with the activity of Acinus‐L higher than that of Acinus‐S’, increase the splicing of a retinoic acid (RA)‐responsive minigene containing a weak 5′ splice site but not a RA‐responsive minigene containing a strong 5′ splice site. RA treatment further enhances the splicing of the weak 5′ splice site by Acinus in a dose‐ and time‐dependent manner, suggesting a RA‐dependent activity in addition to a RA‐independent activity of Acinus. The RA‐independent effect of Acinus occurs to varying degrees using minigene constructs containing several different promoters, while the RA‐dependent splicing activity of Acinus is specific for transcripts derived from the minigene driven by a RA response element (RARE)‐containing promoter. This suggests that the ligand‐dependent splicing activity of Acinus is related to the RA‐activated RAR bound to the RARE. The RRM domain is necessary for the RA‐dependent splicing activity of Acinus and the RA‐independent splicing activity of Acinus is repressed by RNPS1. Importantly, measurement of the splicing of endogenous human RARβ and Bcl‐x in vivo demonstrates that Acinus stimulates the use of the weaker alternative 5′ splice site of these two genes in a RA‐dependent manner for RARβ and a RA‐independent manner for Bcl‐x. Taken together, these studies demonstrate that Acinus functions in both RAR‐dependent splicing and RAR‐dependent transcription. J. Cell. Physiol. 230: 791–801, 2015. © 2014 Wiley Periodicals, Inc.
The Coiled‐Coil Domain Containing 80 (ccdc80) Gene Regulates gadd45β2 Expression in the Developing Somites of Zebrafish as a New Player of the Hedgehog Pathway
Authors: Della Noce Isabella , Carra Silvia , Brusegan Chiara , Critelli Rosina , Frassine Andrea , De Lorenzo Carlo , Giordano Antonio , Bellipanni Gianfranco , Villa Erica , Cotelli Franco , Pistocchi Anna , Schepis Filippo
Published: September 2014

The Coiled‐Coil Domain Containing 80 (CCDC80) gene has been identified as strongly induced in rat thyroid PC CL3 cells immortalized by the adenoviral E1A gene. In human, CCDC80 is a potential oncosoppressor due to its down‐regulation in several tumor cell lines and tissues and it is expressed in almost all tissues. CCDC80 has homologous in mouse, chicken, and zebrafish. We cloned the zebrafish ccdc80 and analyzed its expression and function during embryonic development. The in‐silico translated zebrafish protein shares high similarity with its mammalian homologous, with nuclear localization signals and a signal peptide. Gene expression analysis demonstrates that zebrafish ccdc80 is maternally and zygotically expressed throughout the development. In particular, ccdc80 is strongly expressed in the notochord and it is under the regulation of the Hedgehog pathway. In this work we investigated the functional effects of ccdc80‐loss‐of‐function during embryonic development and verified its interaction with gadd45β2 in somitogenesis. J. Cell. Physiol. 230: 821–830, 2015. © 2014 Wiley Periodicals, Inc.