bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast feeding in HIV: assessing risks in a London clinic
Authors: Patel K , Ghani R , Hartley A , O'Connell R
Published: April 2013

In the UK, national guidelines recommend that all HIV‐positive women should refrain from breastfeeding for prevention of mother to child transmission (PMTCT). However, the World Health Organisation recommends that HIV positive mothers from low income countries should exclusively breastfeed until six months and continue until twelve months with anti‐retroviral therapy (ART) for mother and/or child. In our clinic, a high proportion of HIV positive women are from Africa and mixed messages regarding breast feeding may occur. The decision to not breast feed is sensitive and difficult, particularly where bottle feeding may be associated with HIV. A 2010 BHIVA position statement suggests that in exceptional circumstances breastfeeding may be supported with intense monitoring if the mother has an undetectable viral load. However, there is currently not sufficient evidence regarding transmission or ART toxicity. After a clinic disclosure of breastfeeding at four months post‐delivery, we examined our current practice to investigate how monitoring may need to change if breastfeeding were supported in certain circumstances. A review of notes was undertaken to consider ART and viral load in the post natal‐period to assess potential risks of breastfeeding in our cohort. All HIV‐positive pregnant women who delivered during 2009–10 were eligible. 41 women were identified as having a live delivery of which 30 (73.2%) identified as Black African. 18 (44.0%) were new diagnoses in pregnancy. In total, 28 (68.2%) were on ART, or ART was indicated for the mother, and 13 for PMTCT only (table 1).

BL‐median (IQR)
W12‐median (IQR)
p

Distance at 6MWT (m)
658 (605–691)
715 (IQR 690–830)
<0.0001

DEXA spine (z‐score)
−1.15 (−1.7/−0.7)
−1.05 (−1.4/−0.3)
0.002

DEXA spine (z‐score)(TDF‐treated pts)
−1.4 (−1.7/−0.7)
−1.3 (−1.55/−0.5)
0.002

DEXA femoral neck (z‐score)(walk only)
−0.8 (−1.4/−0.2)
−0.5 (−1.2/−0.2)
0.047

DEXA femoral ward (z‐score)(walk only)
−1 (−1.9/−0.6)
−0.75 (−1.4/−0.2)
0.004

BMI
25.7 (24.6–26.3)
24.9 (21.4−26)
0.0016

Waist circumference (cm)
93 (87−100)
92 (85.5−98.5)
0.029

LDL cholesterol (mg/dL)
126 (113−154.5)
116 (96–137.5)
0.0003

A viral load greater than 100 was found in 4 (9.8%) at delivery. All of the babies delivered were HIV negative. The mean time to post‐delivery viral load was 65.4 days (range 24–584). Of those who were meant to be undetectable on ART, 6/28 (21.4%) had a viral load >100 copies/ml. 12(92.3%) of those who took ART for PMTCT were detectable at post‐delivery viral load. Our clinic review suggests that if breast feeding is to be supported in certain circumstances: i) increased frequency of monitoring will be necessary for those on ART; ii) those on ART for PMTCT only would need to continue ART in the post natal period with such monitoring.
Dolutegravir treatment response by baseline viral load and NRTI backbone in treatment‐naïve HIV‐infected individuals
Authors: Eron J , Rockstroh J , Pozniak A , Elliott J , Small C , Johnson M , Brennan C , Pappa K , Cuffe R ,   SPRING‐2 & SINGLE Study Teams
Published: April 2013

Background

In two 48‐week studies in naïve subjects, dolutegravir with NRTI of choice has shown non‐inferiority to raltegravir and, with ABC/3TC, superiority to Atripla. Factors that influenced choice of NRTIs included viral load, resistance and safety.

Methods

We analysed response rates and time to virologic failure by NRTI backbone and baseline viral load in the pivotal DTG‐naïve studies. SPRING‐2 randomized participants to DTG 50 mg QD or RAL 400 mg BID, each in combination with investigator‐selected NRTIs (TDF/FTC or ABC/3TC). SINGLE randomised participants to DTG 50 mg+ABC/3TC QD or TDF/FTC/EFV (Atripla) QD. In SPRING‐2, changes in serum creatinine were examined by INI and NRTI backbone.

Results

The two studies randomized and treated 1655 subjects, of whom 249 (15%) were female, 388 (23%) non‐white, 495 (30%) had HIV‐1 RNA >100,000 c/ml, and 224 (14%) had CD4+ count <200 cells/mm3.

image

Primary analyses demonstrated non‐inferiority of DTG to RAL in SPRING‐2 (Δ=2.5%; 95% CI:−2.2% to +7.1%, excluding −10%), and superiority of the DTG regimen in SINGLE (7.4%; +2.5% to +12.3%). In SPRING‐2, response rates by NRTI backbone were comparable in each viral load stratum. In SINGLE, a 7% difference in response (favoring DTG+ABC/3TC) was observed in each viral load stratum. Exploratory analyses examining time‐to‐virologic failure showed no difference in response rates between the NRTIs irrespective of baseline viral load or study. Resistance to INIs or NRTIs was not demonstrated in any subject on DTG‐based therapy through 48 weeks. Withdrawals due to AEs on DTG‐based regimen were few (2%) in both studies. In SPRING‐2, no significant differences were observed in serum creatinine change from baseline to Week 48 by NRTI backbones.

Conclusions

In SPRING‐2 and SINGLE, DTG was effective with both ABC/3TC and TDF/FTC, and in subjects with high and low viral load. DTG was well tolerated in both studies. Renal safety also was similar by NRTI backbone. DTG is a once‐daily, unboosted INI that can be used with either TDF/FTC or ABC/3TC backbone in treatment‐naïve, HIV‐infected individuals.
The MAM Rodent Model of Schizophrenia
Authors: Lodge Daniel J.
Published: April 2013

Rodent models of human disease are essential to obtain a better understanding of disease pathology, the mechanism of action underlying conventional treatments, as well as for the generation of novel therapeutic approaches. There are a number of rodent models of schizophrenia based on either genetic manipulations, acute or sub‐chronic drug administration, or developmental disturbances. The prenatal methylazoxymethanol acetate (MAM) rodent model is a developmental disruption model gaining increased attention because it displays a number of histological, neurophysiological, and behavioral deficits analogous to those observed in schizophrenia patients. This unit describes the procedures required to safely induce the MAM phenotype in rats. In addition, we describe a simple behavioral procedure, amphetamine‐induced hyperlocomotion, which can be utilized to verify the MAM phenotype. Curr. Protoc. Neurosci. 63:9.43.1‐9.43.7. © 2013 by John Wiley & Sons, Inc.
Measuring Intravascular Migration of Mouse Ly6Clow Monocytes In Vivo Using Intravital Microscopy
Authors: Carlin L.M. , Auffray C. , Geissmann F.
Published: April 2013

This unit describes methods for intravital imaging of monocytes in the vasculature of the dermis and the mesentery in vivo using fluorescent reporter mice, fluorescent dyes, and antibodies. Cx3cr1gfp/gfp (or +), Rag2−/−, Il2rg−/− mice expressing eGFP at the locus of the Cx3cr1 gene, on the Rag2−/− Il2rg−/− C57Bl/6 background, are used. Although aimed at specifically tracking Ly6Clow monocytes, these protocols could readily be adapted to investigate the interaction of other blood leukocytes with the vascular endothelium by use of other fluorescent reporter mice and fluorescently labeled antibodies. Curr. Protoc. Immunol. 101:14.33.1‐14.33.16. © 2013 by John Wiley & Sons, Inc.
Mouse Model for Pyelonephritis
Authors: Tittel André P. , Heuser Christoph , Kurts Christian
Published: April 2013

This unit describes a simple way to induce pyelonephritis in female mice using uropathogenic Escherichia coli (UPEC). Methods for culturing and preparing working stocks of UPEC are provided. Protocols to measure the bacterial load in the murine kidney following the establishment of pyelonephritis by determining the bacterial colony forming units (CFU) are also included. This assay can be performed with kidney homogenates if the bacterial load is the sole read‐out or if cellular intactness is not required for subsequent assays, or from kidney single cell suspensions prepared by enzymatic digestion. A support protocol describes methods for isolating cells for flow cytometry, ex vivo culture, and other assays. Curr. Protoc. Immunol. 101:15.23.1‐15.23.9. © 2013 by John Wiley & Sons, Inc.
Performances of the Assessment of SpondyloArthritis International Society Axial Spondyloarthritis Criteria for Diagnostic and Classification Purposes in Patients Visiting a Rheumatologist Because of Chronic Back Pain: Results From a Multicenter, Cross‐Sectional Study
Authors: Moltó A. , Paternotte S. , Comet D. , Thibout E. , Rudwaleit M. , Claudepierre P. , van der Heijde D. , Dougados M.
Published: April 2013

Objective

To evaluate the performances (sensitivity, specificity, and positive and negative predictive values) at diagnosis and study visit of the Assessment of SpondyloArthritis international Society (ASAS) criteria in axial spondyloarthritis in patients with chronic back pain (CBP). A secondary objective was to identify the most contributory item to diagnosis/classify spondyloarthritis.

Methods

We conducted a multicenter, cross‐sectional study. Patients were ages <45 years with a history of CBP and seeing a rheumatologist in France. Data included items from the different sets of criteria, checking if present at diagnosis (“diagnosis”)/after diagnosis, but at study visit (“classification”), and the rheumatologist's diagnosis at study visit. Statistical analysis included descriptive characteristics and performances for diagnosis and classification. The diagnosis of the rheumatologist was considered the “gold standard.”

Results

A total of 1,210 patients were eligible for our analysis. Sensitivity and specificity for ASAS axial criteria were 0.76 and 0.94, respectively, and 0.87 and 0.92 for diagnostic and classification purposes, respectively. The positive likelihood ratio of the ASAS axial criteria was 13.6 and 10.30 for diagnostic and classification purposes, respectively. The most contributory items to diagnosis and classification were radiographic sacroiliitis, followed by magnetic resonance imaging sacroiliitis for diagnosis and history of uveitis for classification.

Conclusion

We confirm the validity of the ASAS criteria for both diagnostic and classification purposes in a clinical setting of patients with CBP.
Microstructure Defects Contributing to the Energy Absorption in CrMnNi TRIP Steels
Authors: Borisova Daria , Klemm Volker , Martin Stefan , Wolf Steffen , Rafaja David
Published: April 2013

Microstructure defects control the TRIP effect and/or the TWIP effect and contribute significantly to the absorption of deformation energy in plastically deformed austenitic CrMnNi steels. In this study, the propagation and interaction of dislocations, stacking faults and twins connected with the formation of Lomer‐Cottrell locks, stacking fault tetrahedra, dislocation clusters, deformation bands, microtwins with high‐energy incoherent twin boundaries and the nucleation of α′‐ martensite in the areas of the high local lattice strain due to the fluctuation of the stacking fault density and the lattice shearing, were analysed in the CrMnNi TRIP steel after different deformation extents via transmission electron microscope with high resolution and via scanning electron microscope.
Imprinted microspheres doped with carbon nanotubes as novel electroresponsive drug‐delivery systems
Authors: Puoci Francesco , Hampel Silke , Parisi Ortensia ilaria , Hassan Abdelwahab , Cirillo Giuseppe , Picci Nevio
Published: April 2013

Novel molecularly imprinted polymers (MIPs) suitable for the electroresponsive release of diclofenac were synthesized by precipitation polymerization in the presence of carbon nanotubes (CNTs). Both conventional and electroresponsive imprinted polymers were synthesized with methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the crosslinker. Preliminary experiments were performed to fully characterize the conventional MIPs and composite materials in terms of their morphological properties, recognition behavior, and electric resistivity. In vitro release experiments were performed in aqueous media to elucidate the ability of the MIPs and spherical imprinted polymers doped with CNTs to release the loaded template in a sustained manner over time in comparison to the that of the corresponding nonimprinted materials. Furthermore, a 20‐V direct‐current voltage was applied through the releasing media to evaluate how the electric field influenced the drug release to demonstrate the suitability of the proposed macromolecular system as an electroresponsive drug‐delivery device. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 829‐834, 2013
Thermally induced microstructural changes and its influence on electrical conductivity of a polymer‐based bakelite RPC detector material: A positron lifetime study
Authors: Veedu Aneesh Kumar Kottaran , Basavaraju Ravikumar Harijan , Chikkakuntappa Ranganathaiah
Published: April 2013

Annealing studies have been carried out to understand the temperature induced microstructural changes in Bakelite (P‐120 NEMA LI‐1989 Grade XXX) Resistive Plate Chamber (RPC) detector material using Positron annihilation lifetime spectroscopy (PALS), Fourier transform infrared spectroscopy (FTIR), and XRD. The variation of positron lifetime parameters viz., ortho‐Positronium lifetime (τ3) and free volume size (Vf) increases marginally above glass transition temperature Tg as a result of structural changes due to segmental mobility. The drastic increase of free volume parameters above 240°C attributed to the reduction in strength of C—H bond of the aliphatic bridges and cleavage of methylene bridges of the polymer network, which is supported by the FTIR results. The XRD results show the reduction in crystallinity and average crystallite size of Bakelite on annealing correlates well with the free volume and electrical conductivity. The temperature induced electrical conductivity and activation energy is also correlated with the positron lifetime parameters. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 793‐800, 2013
How useful is YouTube in learning heart anatomy?
Authors: Raikos Athanasios , Waidyasekara Pasan
Published: April 2013

Nowadays more and more modern medical degree programs focus on self‐directed and problem‐based learning. That requires students to search for high quality and easy to retrieve online resources. YouTube is an emerging platform for learning human anatomy due to easy access and being a free service. The purpose of this study is to make a quantitative and qualitative analysis of the available human heart anatomy videos on YouTube. Using the search engine of the platform we searched for relevant videos using various keywords. Videos with irrelevant content, animal tissue, non‐English language, no sound, duplicates, and physiology focused were excluded from further elaboration. The initial search retrieved 55,525 videos, whereas only 294 qualified for further analysis. A unique scoring system was used to assess the anatomical quality and details, general quality, and the general data for each video. Our results indicate that the human heart anatomy videos available on YouTube conveyed our anatomical criteria poorly, whereas the general quality scoring found borderline. Students should be selective when looking up on public video databases as it can prove challenging, time consuming, and the anatomical information may be misleading due to absence of content review. Anatomists and institutions are encouraged to prepare and endorse good quality material and make them available online for the students. The scoring rubric used in the study comprises a valuable tool to faculty members for quality evaluation of heart anatomy videos available on social media platforms. Anat Sci Educ. 7: 12–18. © 2013 American Association of Anatomists.
Exploring behavioral transfer from knowledge seeking to knowledge contributing: The mediating role of intrinsic motivation
Authors: Yan Yalan , Davison Robert M.
Published: April 2013

Knowledge contributing has long been identified as a bottleneck in knowledge management since individuals tend to believe that their contributing would not be worth the effort, given high levels of expectation to receive some value in return. Self‐perception theory posits that individuals come to “know” their own internal beliefs by inferring them partially from observations of their own overt behavior. Building on self‐perception theory and adhering to the principle that the relationship between behavior and beliefs is one of mutual influence, we develop a research model to explore the behavioral transfer from knowledge seeking to knowledge contributing and consider the mediating effect of intrinsic motivation. Data collected from 430 users of Web 2.0 applications were used to test the model. The mediating role of intrinsic motivation between knowledge seeking and knowledge contributing is confirmed. These findings and their implications for theory and practice are discussed.
Facile Hydrogen‐Bond‐Assisted Polymerization and Immobilization Method to Synthesize Hierarchical Fe3O4@Poly(4‐vinylpyridine‐co‐divinylbenzene)@Au Nanostructures and Their Catalytic Applications
Authors: Guo Wanchun , Wang Qian , Wang Ge , Yang Mu , Dong Wenjun , Yu Jie
Published: April 2013

Hierarchical Fe3O4@poly(4‐vinylpyridine‐co‐divinylbenzene)@Au (Fe3O4@P(4‐VP–DVB)@Au) nanostructures were fabricated successfully by means of a facile two‐step synthesis process. In this study, well‐defined core–shell Fe3O4@P(4‐VP–DVB) microspheres were first prepared with a simple polymerization method, in which 4‐VP was easily polymerized on the surface of Fe3O4 nanoparticles by means of strong hydrogen‐bond interactions between COOH groups on poly(acrylic acid)‐modified Fe3O4 nanoparticles and a 4‐VP monomer. HAuCl4 was adsorbed on the chains of a P(4‐VP) shell and then reduced to Au nanoparticles by NaBH4, which were embedded into the P(4‐VP) shell of the composite microspheres to finally form the Fe3O4@P(4‐VP–DVB)@Au nanostructures. The obtained Fe3O4@P(4‐VP–DVB)@Au catalysts with different Au loadings were applied in the reduction of 4‐nitrophenol (4‐NP) and exhibited excellent catalytic activity (up to 3025 h−1 of turnover frequency), facile magnetic separation (up to 31.9 emu g−1 of specific saturation magnetization), and good durability (over 98 % of conversion of 4‐NP after ten runs of recyclable catalysis and almost negligible leaching of Au).
Robust Adaptive Dynamic Surface Control for a Class of MIMO Nonlinear Systems with Unknown Non‐Symmetric Dead‐Zone
Authors: Wang Chenliang , Lin Yan
Published: April 2013

This paper is devoted to adaptive output tracking for a class of multi‐input multi‐output nonlinear systems with unknown non‐symmetric dead‐zone. With the aid of a matrix factorization and a similarity transformation, a robust adaptive dynamic surface control scheme is proposed and the difficulty caused by the control gain matrix and the dead‐zone is circumvented. By introducing a surface error modification and an initialization technique, we show that the performance of the tracking errors can be guaranteed. Moreover, the proposed scheme contains only one updated parameter at each design step, which significantly reduces the computational burden. It is proven that all signals of the closed‐loop system are semi‐globally uniformly bounded. Simulation results on coupled inverted double pendulums are presented to illustrate the effectiveness of the proposed scheme.
Micelle‐enhanced spectrofluorimetric method for determination of sitagliptin and identification of potential alkaline degradation products using LC‐MS
Authors: Salim MM , El‐Enany N , Belal F , Walash MI , Patonay G
Published: April 2013

A novel, quick, simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of sitagliptin (SG) in its pharmaceutical formulations. The proposed method is based on investigation of the fluorescence spectral behavior of sitagliptin in an SDS micellar system. In an aqueous solution of phosphate buffer pH 4.0, the fluorescence intensity of SG in the presence of SDS was greatly enhanced, by 200%, i.e. twofold enhancement. The fluorescence intensity of SG was measured at 300 nm after excitation at 270 nm. The method showed good linearity in the range 0.03–10.0 µg/mL with a good correlation coefficient (r = 0.9998). The limits of detection and quantitation values were 5.31 and 16.1 ng/mL, respectively. The proposed method was successfully applied to the analysis of SG in its single and co‐formulated commercial tablets; the results were in good agreement with those obtained using a reference method. Application of the proposed method was extended to stability studies of SG after exposure to different forced degradation conditions according to the ICH guidelines, such as acidic, alkaline, thermal, photo‐ and oxidative stress. The chemical structure of certain potential degradation products (DPs) were investigated using LC‐MS. Copyright © 2013 John Wiley & Sons, Ltd.
Neuroanatomical and neuropharmacological approaches to postictal antinociception‐related prosencephalic neurons: the role of muscarinic and nicotinic cholinergic receptors
Authors: de Freitas Renato Leonardo , Bolognesi Luana Iacovelo , Twardowschy André , Corrêa Fernando Morgan Aguiar , Sibson Nicola R. , Coimbra Norberto Cysne
Published: April 2013

Several studies have suggested the involvement of the hippocampus in the elaboration of epilepsy. There is evidence that suggests the hippocampus plays an important role in the affective and motivational components of nociceptive perception. However, the exact nature of this involvement remains unclear. Therefore, the aim of this study was to determine the role of muscarinic and nicotinic cholinergic receptors in the dorsal hippocampus (dH) in the organization of postictal analgesia. In a neuroanatomical study, afferent connections were found from the somatosensory cortex, the medial septal area, the lateral septal area, the diagonal band of Broca, and the dentate gyrus to the dH; all these areas have been suggested to modulate convulsive activity. Outputs to the dH were also identified from the linear raphe nucleus, the median raphe nucleus (MdRN), the dorsal raphe nucleus, and the locus coeruleus. All these structures comprise the endogenous pain modulatory system and may be involved either in postictal pronociception or antinociception that is commonly reported by epileptic patients. dH‐pretreatment with cobalt chloride (1.0 mmol/L CoCl2/0.2 μL) to transiently inhibit local synapses decreased postictal analgesia 10 min after the end of seizures. Pretreatment of the dH with either atropine or mecamylamine (1.0 μg/0.2 μL) attenuated the postictal antinociception 30 min after seizures, while the higher dose (5.0 μg/0.2 μL) decreased postictal analgesia immediately after the end of seizures. These findings suggest that the dH exerts a critical role in the organization of postictal analgesia and that muscarinic and nicotinic cholinergic receptor‐mediated mechanisms in the dH are involved in the elaboration of antinociceptive processes induced by generalized tonic‐clonic seizures.
Steady‐State Multiplicity in High‐Pressure Bubble Column Reactors
Authors: Shaikh A. A. , Binous H.
Published: April 2013

The effect of pressure on the possible existence of multiple steady states in bubble column reactors is investigated. A mathematical model involving fast pseudo first‐order kinetics is employed to describe the performance of non‐isobaric, non‐isothermal reactors. The numerical analysis reveals that the existence of multiplicity is sensitive to pressure variation, yet high‐pressure operating conditions do not necessarily lead to a higher likelihood of multiplicity in these contactors.
Numerical Study of the Solid Volume Fraction and Pressure Drop of Fibrous Media by Response Surface Methodology
Authors: Zhu X. , Qian F. , Lu J. , Zhang H.
Published: April 2013

In order to establish a realistic fibrous media structure, internal microscopic cross‐sectional images were taken by scanning electron microscopy and then processed by Matlab. Finally, the 3D models of the fibrous media were reconstructed using Gambit software. The influences of structural parameters of the fibrous media on solid volume fraction and pressure drop were analyzed by response surface methodology, and the internal gas flow fields of the fibrous media were simulated using Ansys Fluent. The simulation results of the pressure drop are in good agreement with the Davies experimental correlation data.
Methane Hydrate Formation and Dissociation in the presence of Bentonite Clay Suspension
Authors: Kumar Saw V. , Udayabhanu G. N. , Mandal A. , Laik S.
Published: April 2013

The present work reports the effect of bentonite clay on methane hydrate formation and dissociation in synthetic seawater of salinity 3.55 % of total dissolved salts. Extensive observations of pressure‐temperature equilibrium during formation and decomposition of methane hydrate under different conditions have been made. It is observed that phase equilibrium conditions of hydrate are affected on changing the concentration of bentonite clay in synthetic seawater. Induction time for hydrate nucleation has been measured under different concentrations of clay and subcooling conditions. The presence of bentonite clay in synthetic seawater reduces the induction time of hydrate formation. Enthalpy of hydrate dissociation is calculated by Clausius‐Clapeyron equation using measured phase equilibrium data. The amount of gas consumed during hydrate formation has been calculated using real gas equation. It is found that a larger amount of gas is consumed upon addition of bentonite clay in synthetic seawater.
Metathesis of Ethene and Decene to Propene over a WO3/SiO2 Catalyst
Authors: Chen S.‐L. , Wang Y. , Yuan G. , Hua D. , Zheng M. , Zhang J.
Published: April 2013

Metathesis between decene and ethene to propene over a WO3/SiO2 catalyst was studied. The dependency of the conversion of decene, selectivity to propene, and working lifetime of the catalyst on ethane‐to‐decene molar ratio and temperature was evaluated. Low temperature was found to be favorable to the production of C6–C9 olefins, while high temperature enhanced C10+ olefins. The working lifetime of the catalyst decreased with the weight hourly space velocity. The optimum reaction conditions for the metathesis process of decene and ethene to propene were determined. An obvious induction period was found to exist in the metathesis reaction.
Safety and efficacy of adjuvant pegylated interferon therapy for metastatic tumor antigen 1‐positive hepatocellular carcinoma
Authors: Lee Danbi , Chung Young‐Hwa , Kim Jeong A. , Park Won Hyung , Jin Young‐Joo , Shim Ju Hyun , Ryu Soo Hyung , Jang Myoung Kuk , Yu, Eunsil , Lee Young Joo
Published: April 2013

BACKGROUND

Metastatic tumor antigen 1 (MTA1) overexpression is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). It has been suggested that pegylated interferon (Peg‐IFN) can prevent the occurrence of HCC in patients who have chronic viral hepatitis. In this study, the authors examined whether postoperative adjuvant Peg‐IFN therapy can reduce the recurrence of MTA1‐positive HCC after curative surgical resection.

METHODS

In this case‐control study, 93 patients with MTA1‐positive HCC who underwent curative surgical resection were prospectively enrolled. The median patient age was 53 years (range, 27‐78); there were 65 men and 28 women; the etiology was hepatitis B virus (HBV) in 77 patients, hepatitis C virus (HCV) in 6 patients, and non‐HBV/non‐HCV in 10 patients; 31 patients received Peg‐IFN (Peg‐INTRON®) subcutaneously at a dose of 50 μg per week for 12 months (the Peg‐IFN group); and the remaining 62 patients were followed only and did not receive any adjuvant therapies (control group). Patients were followed every 1 to 3 months for a median of 24 months.

RESULTS

HCC recurred postoperatively in 26 of 93 patients (28%), and 9 patients (10%) died during follow‐up. The overall cumulative recurrence rates were significantly lower in the Peg‐IFN group than in the control group (7% and 14% vs 24% and 34% at 1 year and 2 years, respectively; P < .05). In addition, the 1‐year and 2‐year cumulative survival rates were higher in the Peg‐IFN group compared with the control group (100% vs 93% and 100% vs 87%, respectively; P < .05). In multivariate analysis, the receipt of adjuvant Peg‐IFN therapy, in addition to having a lower Cancer of the Liver Italian Program score and being a woman, was an independent, favorable factor for a lower risk of postoperative recurrence.

CONCLUSIONS

The current data indicate that adjuvant Peg‐IFN therapy may reduce the recurrence of HCC in patients who have MTA1‐positive HCC after curative surgical resection. Cancer 2013;119:2239–2246. © 2013 American Cancer Society.
Proton‐Coupled Self‐Assembly of a Porphyrin‐Naphthalenediimide Dyad
Authors: Tu Siyu , Kim Se Hye , Joseph Jojo , Modarelli David A. , Parquette Jon R.
Published: April 2013

The construction of an n–p heterojunction through the self‐assembly of a dyad based on tetraphenylporphyrin (TPP) and 1,4,5,8‐naphthalenedimide (NDI) (1) is described. Proton transfer from the lysine head group of 1 to the porphyrin ring occurs concomitantly with self‐assembly into 1D nanorods in CHCl3. TEM and AFM studies showed that the nanorods are formed by the lateral and vertical fusion of multilameller vesicles into networks and hollow ribbons, respectively. These intermediate structures transitioned to nanorods over the course of 4–6 days. Time‐resolved spectroscopy revealed that photoinduced charge separation occurs with rate constants that depend on the nature of the aggregation.
Postsynthetic Modification of a Metal–Organic Framework (MOF) Structure for Enantioselective Catalytic Epoxidation
Authors: Candu Natalia , Tudorache Mădălina , Florea Mihaela , Ilyes Elena , Vasiliu Florin , Mercioniu Ionel , Coman Simona M. , Haiduc Ionel , Andruh Marius , Pârvulescu Vasile I.
Published: April 2013

Postsynthetic modification of [Cu2(mand)2(hmt)] (mand=mandelic acid, hmt=hexamethylenetetramine) with a chiral, dimeric chromium(III)–salen complex led to a robust structure. Characterization of this new material showed that it perfectly preserved the textural and structural properties of the parent metal–organic framework (MOF). Although epoxidation of trans‐methyl cinnamate with hydrogen peroxide led to copper leaching of 2–3 %, experiments performed with N‐methylmorpholine‐N‐oxide indicated no leaching, even after 72 h of exposure. The obtained chiral MOF is an effective catalyst for the enantioselective epoxidation of trans‐methyl cinnamate and leads to (2R,3S)‐phenylglycidate with a high enantiomeric excess at room temperature.
Frequency acquisition synchronization for multiple antenna systems
Authors: Ma Chixiang , Lin Ping
Published: April 2013

In this paper, we consider the problem of frequency acquisition synchronization by using multiple antennas over wireless fading channels. We introduce frequency synchronization with different combining schemes including space diversity and time diversity. Their performance is estimated for a Rayleigh fading channel with an analysis both theoretically and by simulation. We investigate the relationship between the mean squared error (MSE) and the average signal‐to‐noise ratio (SNR) for combining of different blocks and antennas. Both the carrier frequency offset and the sampling frequency offset are estimated when multiple antennas are utilized for signal transmission. The estimation with maximum ratio combining (MRC) scheme is presented in detail, and the estimation with selection combining scheme and equal gain combining scheme are introduced briefly. The simulation results explicitly show that the performance of the frequency acquisition synchronization with MRC scheme is better than that of others and that the MSE at low SNR is not very close to the Cramér–Rao low bound in multiblock combining frequency synchronization. Furthermore, the results address that in order to improve the performance, the total number of receive antennas will be increased exponentially. Copyright © 2013 John Wiley & Sons, Ltd.
On the Reactivity of Silylboranes toward Lewis Bases: Heterolytic B–Si Cleavage vs. Adduct Formation
Authors: Kleeberg Christian , Borner Corinna
Published: April 2013

Silylboranes are important reagents in a variety of catalytic silylation and silaboration reactions. While transition‐metal‐catalyzed reactions are well established, organo‐/Lewis base‐catalyzed reactions of silylboranes have only recently emerged. For both catalytic processes the reactivity of silylboranes toward Lewis bases is of relevance. While for organo‐catalyzed reactions Lewis base activation of the silylborane has been proposed, transition‐metal‐ and especially copper‐catalyzed reactions also frequently require the presence of Lewis basic alkali metal alkoxides. In the present study we explore the reaction of K(18‐crown‐6) tert‐butoxide and the NHC 1,3‐diisopropyl‐4,5‐dimethyl‐imidazol‐2‐ylidene as exemplary Lewis bases with the two silylboranes pinB‐SiMe2Ph and pinB‐SiPh3 (pin = OCMe2CMe2O). The reaction with K(18‐crown‐6) tert‐butoxide results in activation of the boron–silicon bond. The isolated product of this activation is either the potassium silyl complex [K(18‐crown‐6)SiPh3] or [K(18‐crown‐6)(thf)2][pinB(SiMe2Ph)2], the formal Lewis acid/base adduct of [K(18‐crown‐6)SiMe2Ph] with pinB‐SiMe2Ph. Both complexes react essentially as sources of nucleophilic silyl moieties in reactions with exemplary electrophiles. In contrast, usage of the carbene leads to the formation of isolable Lewis acid/base adducts of the type (NHC)pinB‐SiR3, which do not react as sources of nucleophilic silyl moieties. The identification and characterization of these species appears of relevance for the mechanistic understanding and further development of Lewis base/organo‐ as well as transition‐metal‐catalyzed silyl transfer reactions.
Total Syntheses of Eudistomins Y1–Y7 by an Efficient One‐Pot Process of Tandem Benzylic Oxidation and Aromatization of 1‐Benzyl‐3,4‐dihydro‐β‐Carbolines
Authors: Trieu Tien Ha , Dong Jing , Zhang Qiang , Zheng Bo , Meng Tian‐Zhuo , Lu Xia , Shi Xiao‐Xin
Published: April 2013

The first total synthesis of eudistomin Y7 (7) and total syntheses of eudistomins Y1–Y6 (1–6) are described. An efficient room‐temperature conversion of 1‐benzyl‐3,4‐dihydro‐β‐carbolines (11) into 1‐benzoyl‐β‐carbolines (14) by a one‐pot process of tandem benzylic oxidation and aromatization as the key step of these total syntheses was also studied in detail.
Gasification of Low‐Grade Coal in a Dual Fluidized‐Bed Steam Gasifier
Authors: Kern Stefan , Pfeifer Christoph , Hofbauer Hermann
Published: April 2013

The gasification of a bituminous coal was performed in a dual fluidized‐bed (DFB) steam gasifier at a fuel power of 90 kWth. The main aim of these tests was to prove the suitability of the DFB system for cheap low‐grade coals that are often delivered with a wide range of particle sizes and ash loads. The fine fraction in particular can become entrained in the gas stream and thus be responsible for changes in the system performance and gas quality. The selected gasifier bed material was olivine, with an applied particle size of 375 μm, the steam‐to‐carbon ratio was 1.3 kg kgC−1, and the gasification temperature was 850 °C. In addition to standard online analysis of the main components of the product gas, impurities that included NH3, H2S, and tar were also examined.
Change in antipsychotic usage pattern and risk of relapse in older patients with schizophrenia
Authors: Talaslahti Tiina , Alanen Hanna‐Mari , Hakko Helinä , Isohanni Matti , Häkkinen Unto , Leinonen Esa
Published: April 2013

Objective

The aim of this study was to explore the use of first (FGAs) and second generation antipsychotics (SGAs) in older outpatients with schizophrenia and schizoaffective disorder. Factors associated with schizophrenic relapses were also studied.

Methods

The study sample consisting of 8792 patients aged 64 years or more was collected from Finnish nationwide registers. The register data on the use of FGAs and SGAs were followed up between 1998 and 2003. Factors associated with psychiatric hospitalization in 1999 indicating relapse were studied using logistic regression analysis.

Results

The use of SGAs increased from 2.8% to 12.4%, and the use of FGAs decreased from 57.5% to 39.4%. The use of a combination of SGAs and FGAs increased from 4.0% to 8.5%. The proportion of those who did not buy any antipsychotics varied between 35.8% and 39.7%. The number of patients hospitalized on psychiatric wards within a year (1999; relapsed) was 8.8%. Factors independently associated with relapse were use of combined FGAs and SGAs [odds ratio (OR) 1.70, p = 0.001] and use of antidepressants (OR 1.27, p = 0.019). Diagnosis of cardiovascular disease was negatively associated with risk of schizophrenic relapse (OR 0.84, p = 0.040).

Conclusion

The use of SGAs increased while the use of FGAs decreased in older outpatients with schizophrenia. Almost 40% of the study sample did not use any antipsychotic medication. The 1‐year relapse rate was 8.8%. Several factors, such as combined use of FGAs and SGAs, or antidepressants, were associated with schizophrenic relapse, whereas cardiovascular disease showed a negative association with the relapse. Copyright © 2013 John Wiley & Sons, Ltd.
Polymorphisms influencing olanzapine metabolism and adverse effects in healthy subjects
Authors: Cabaleiro Teresa , López‐Rodríguez Rosario , Ochoa Dolores , Román Manuel , Novalbos Jesús , Abad‐Santos Francisco
Published: April 2013

Objective

The pharmacokinetics of olanzapine and response to treatment could be affected by polymorphisms in genes coding for drug‐metabolizing enzymes, transporters, or receptors. The aim of this study was to identify genetic markers predictive of pharmacokinetics, pharmacodynamics, and adverse effects of olanzapine.

Methods

Sixty‐three healthy volunteers receiving a single 5‐mg oral dose of olanzapine were genotyped for 39 genetic variants that could be related to the response to olanzapine. All genetic variants were analyzed by PharmaChip, but DRD2 Taq1A polymorphism was determined by real‐time polymerase chain reaction. Olanzapine was measured using high‐performance liquid chromatography combined with tandem mass spectrometry. The relationship of gender and polymorphisms with olanzapine pharmacokinetics, the change in prolactin levels, and the incidence of adverse effects were evaluated by multiple regression analysis.

Results

The pharmacokinetics of olanzapine was influenced by polymorphisms in CYP3A5, GSTM3, and GRIN2B. Prolactin levels were affected by gender and polymorphisms in DRD2 and 5‐HTR2A. Polymorphisms in CYP2C9, TPMT, UGT1A1, MDR1, and 5‐HTR2A were related to some adverse effects of olanzapine.

Conclusions

Several polymorphisms can explain differences in the pharmacokinetics, pharmacodynamics, and safety of olanzapine in healthy subjects. Whether these genetic factors influence the risk of therapeutic failure or tolerability in patients remains to be established. Copyright © 2013 John Wiley & Sons, Ltd.
Micro‐nanopatterning as tool to study the role of physicochemical properties on cell–surface interactions
Authors: Singh Ajay Vikram , Patil Rajendra , Thombre Dipalee K. , Gade W. N.
Published: April 2013

The current nano‐biotechnologies interfacing synthetic materials and cell biology requires a better understanding of cell–surface interactions on the micro‐to‐nanometer scale. Cell–substrate interactions are mediated by the presence of proteins adsorbed from biological fluids to the substrate. The effect of nanotopography and surface chemistry on protein adsorption as well as the mediation effect on subsequent cellular communication with substratum is not well documented. This review discusses the role of physicochemical properties of cell–surface interactions and state‐of‐the‐art methods currently available for micro‐nanoscale surface fabrication and patterning. We also briefly discuss the current surface patterning techniques that allow the combination of a fine and independent control on nanotopography and chemistry to understand the effect of surface nanoscale substrate morphology on cell–surface interactions which has never been realized in previous reports. In addition, we discuss the influence of various chemical patterning and modulation of the nano‐topography of surfaces on cell functionality and phenotype. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3019–3032, 2013.
Cell biological responses of osteoblasts on anodized nanotubular surface of a titanium‐zirconium alloy
Authors: Sista Subhash , Nouri Alireza , Li Yuncang , Wen Cuie , Hodgson Peter D. , Pande Gopal
Published: April 2013

Anodization of titanium and its alloys, under controlled conditions, generates a nanotubular architecture on the material surface. The biological consequences of such changes are poorly understood, and therefore, we have analyzed the cellular and molecular responses of osteoblasts that were plated on nanotubular anodized surface of a titanium‐zirconium (TiZr) alloy. Upon comparing these results with those obtained on acid etched and polished surfaces of the same alloy, we observed a significant increase in adhesion and proliferation of cells on anodized surfaces as compared to acid etched or polished surface. The expression of genes related to cell adhesion was high only on anodized TiZr, but that of genes related to osteoblast differentiation and osteocalcin protein and extracellular matrix secretion were higher on both anodized and acid etched surfaces. Examination of surface morphology, topography, roughness, surface area and wettability using scanning electron microscopy, atomic force microscopy, and contact angle goniometry, showed that higher surface area, hydrophilicity, and nanoscale roughness of nanotubular TiZr surfaces, which were generated specifically by the anodization process, could strongly enhance the adhesion and proliferation of osteoblasts. We propose that biological properties of known bioactive titanium alloys can be further enhanced by generating nanotubular surfaces using anodization. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3416–3430, 2013.
Regulation of intracellular pH by glycosaminoglycans
Authors: Kathagen Nadine , Prehm Peter
Published: April 2013

The intracellular pH is regulated by a delicate balance of ion distribution across the plasma membrane and the physico‐chemical properties of intra‐ and extracellular components. We analyzed the effects of glycosaminoglycans on the intracellular pH of fibroblasts by using the fluorescent pH indicator BCECF‐AM. Addition of hyaluronan, hyaluronan oligosaccharides, chondroitin sulfate, or heparin to the culture medium of fibroblasts caused intracellular acidification from pH 7.2 to 6.7 in a concentration dependent manner. High molecular weight hyaluronan acidified more than hyaluronan oligosaccharides at the same concentrations. Hyaluronidase treatment or inhibition of hyaluronan export with xanthohumol led to intracellular alkalization. These observations indicated that extracellular glycosaminoglycans participate in intracellular pH regulation. The mechanism was explained by Donnan effects and molecular crowding. J. Cell. Physiol. 228: 2071–2075, 2013. © 2013 Wiley Periodicals, Inc.
Small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor‐β1
Authors: Moon Mi‐Young , Kim Hee‐Jun , Kim Jae‐Gyu , Lee Jae‐Yong , Kim Jaebong , Kim Sung‐Chan , Choi Ihn‐Geun , Kim Pyeung‐Hyeun , Park Jae‐Bong
Published: April 2013

Transforming growth factor (TGF)‐β1 regulates diverse cellular functions. Particularly, TGF‐β1 induces monocyte migration to sites of injury or inflammation in early period, whereas TGF‐β1 inhibits cell migration in late phase. In this study, we attempted to understand how TGF‐β1 suppresses cell migration in late phase. We found that TGF‐β1 of short exposure induces the production of chemokines, such as macrophage inflammatory protein (MIP)‐1α, by Raw 264.7 cells. However, knock‐down of small GTPase RhoA by sh‐RhoA inhibited the production of MIP‐1α and macrophage migration, suggesting that RhoA is essential for expression of this chemokine. An activator of Epac (exchange proteins directly activated by cAMP; a guanine nucleotide exchange factor of Rap1), 8CPT‐2Me‐cAMP which leads to Rap1 activation abrogated MIP‐1α expression and macrophage migration. Indeed, GTP‐RhoA and GTP‐Rap1 levels were reciprocally regulated in a time‐dependent manner following TGF‐β1 stimulation. 8CPT‐2Me‐cAMP suppressed GTP‐RhoA levels, whereas si‐Rap1 augmented GTP‐RhoA levels and cell migration. TGF‐β1 produced cAMP in late period and si‐RNAs of Epac1 and Epac2 reduced GTP‐Rap1 levels leading to promotion of GTP‐RhoA levels. Furthermore, si‐RNA of ARAP3 (Rap‐dependent RhoGAP) increased GTP‐RhoA level and cell migration. Therefore, we propose the mechanism that prolonged TGF‐β1 treatment produce cAMP, which activates sequentially Epac, Rap1 and ARAP3, resulting in suppression of RhoA, chemokine expression, and macrophage migration. Contrary to the general concept that Rap1 stimulates cell migration, we demonstrated in this study that Rap1 inhibits cell migration by suppression of RhoA activity in response to TGF‐β1. J. Cell. Physiol. 228: 2119–2126, 2013. © 2013 Wiley Periodicals, Inc.
Reaction of 1,2‐Dialkyldiaziridines and 1,2,3‐Trialkyldiaziridines with Methyl Propiolate in Ionic Liquids and in Organic Solvents
Authors: Petukhova Vera Yu. , Fershtat Leonid L. , Kachala Vadim V. , Kuznetsov Vladimir V. , Khakimov Dmitriy V. , Pivina Tatyana S. , Makhova Nina N.
Published: April 2013

An interaction of 1,2‐dialkyldiaziridine and 1,2,3‐trialkyldiaziridine with methyl propiolate was studied both in organic solvent (MeCN, CH2Cl2, C6H6) and in ionic liquids. Earlier unknown linear structures, in which three molecules of methyl propiolate were suited to one diaziridine molecule (adducts 1 : 3), were obtained in MeCN. The diaziridine ring expansion products 1,2,3,4‐tetrahydropyrimidine derivatives (adducts 1 : 2) and, along with them in some cases, the same linear structures were obtained in ionic liquids. A mechanism of reactions found was offered. The regioselectivity of reactions was supposed to determine by the structure of substituents in initial diaziridines. This conclusion was supported by quantum chemical calculations.
Effects of age and sex on the concentrations of glutamate and glutamine in the human brain
Authors: Hädel Sven , Wirth Christoph , Rapp Michael , Gallinat Jürgen , Schubert Florian
Published: April 2013

Purpose

To determine the effects of age and sex on cerebral glutamate and glutamine concentrations in a large sample of healthy humans using a dedicated measuring and evaluation procedure. Exploratory examinations of other brain metabolites were also conducted.

Materials and Methods

In 118 healthy subjects aged 19 to 55 years (59 female) absolute concentrations of glutamate, glutamine, N‐acetylaspartate (NAA), total creatine, and total choline (tCho) in voxels comprising the left hippocampus (HC) and the anterior cingulate cortex (ACC) were investigated using point‐resolved spectroscopy with an echo time of 80 ms at 3 Tesla in combination with a reliable quantification procedure. Special care was taken to correct for multiple comparisons.

Results

An age‐related decline of the concentrations of glutamate in both regions studied was observed whereas glutamine levels in ACC increased with age. Statistically significant sex‐related differences were detected for glutamate in the HC and for tCho in the ACC. NAA decreased with age in both regions, the significance not surviving Bonferroni correction.

Conclusion

The results demonstrate effects of age and gender on glutamate, glutamine, choline containing compounds, and NAA in healthy human brain. They add to the growing evidence for gender‐specific differences in cerebral neurotransmission, metabolism, and structure across the lifespan. J. Magn. Reson. Imaging 2013;38:1480–1487. © 2013 Wiley Periodicals, Inc.