bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors for Pain in Patients With Different Grades of Knee Osteoarthritis
Authors: Schiphof Dieuwke , Kerkhof Hanneke J. M. , Damen Jurgen , de Klerk Bianca M. , Hofman Albert , Koes Bart W. , van Meurs Joyce B. J. , Bierma‐Zeinstra Sita M. A.
Published: November 2012

Objective

Discordance between having pain and radiologic osteoarthritis (OA) is a well‐established fact. It is suggested that this particularly applies to the less severe grades of OA. However, some people with a Kellgren/Lawrence (K/L) grade of 3 or 4 for OA are without pain. This study aimed to identify factors and differences in the factors associated with pain in persons with different grades of knee OA.

Methods

We stratified the knees of more than 5,000 participants of a population‐based cohort study, the Rotterdam Study, based on the grade of knee OA. Multivariate generalized estimating equation analysis was used to analyze the association with knee pain. We tested several factors not directly related to structural damage of the knee.

Results

As expected, an increasing percentage of participants did not report pain with decreasing severity of knee OA: 25.8% for K/L grade 3 or 4 and 84.5% for no knee OA. Being a woman, having widespread pain, reporting general health symptoms, familial OA, and morning stiffness are factors for knee pain, but not specific for a particular grade of radiographic knee OA. Depression and hip OA showed significant interactions with the grade of OA being a factor for knee pain in knees without OA (K/L grade 0), but not in knees with OA. In addition, increasing age is protective for reporting pain in general.

Conclusion

Several factors are associated with knee pain, but are not specific for a grade of radiographic knee OA. Two factors were associated with knee pain in the knee without signs of OA.
A Universal Scheme for Patterning of Oxides via Thermal Nanoimprint Lithography
Authors: Dinachali Saman Safari , Saifullah Mohammad S. M. , Ganesan Ramakrishnan , Thian Eng San , He Chaobin
Published: November 2012

Direct patterning of oxides using thermal nanoimprint lithography is performed using either the sol‐gel or methacrylate route. The sol‐gel method results in resists with long shelf‐life, but with high surface energy and a considerable amount of solvent that affects the quality of imprinting. The methacrylate route, which is limited to certain oxides, produces polymerizable resists, leading to low surface energy, but suffers from the shorter shelf‐life of precursors. By combining the benignant elements from both these routes, a universal method of direct thermal nanoimprinting of oxides is demonstrated using precursors produced by reacting an alkoxide with a polymerizable chelating agent such as 2‐(methacryloyloxy)ethyl acetoacetate (MAEAA). MAEAA possesses β‐ketoester, which results in the formation of environmentally stable, chelated alkoxide with long shelf‐life, and methacrylate groups, which provide a reactive monomer pendant for in situ copolymerization with a cross‐linker during imprinting. Polymerization leads to trapping of cations, lowering of surface energy, strengthening of imprints, which enables easy and clean demolding over 1 cm × 2 cm patterned area with ≈100% yield. Heat‐treatment of imprints gives amorphous/crystalline oxide patterns. This alliance between two routes enables the successful imprinting of numerous oxides including Al2O3, Ga2O3, In2O3, Y2O3, B2O3, TiO2, SnO2, ZrO2, GeO2, HfO2, Nb2O5, Ta2O5, V2O5, and WO3.
Combined factor IX and protein C deficiency in a child: Thrombogenic effects of two factor IX concentrates
Authors: Negrier Claude , Vial Jean , Vinciguerra Christine , Berruyer Micheline , Dechavanne Marc
Published: November 2012

We have recently described an unusual situation which involved a combination of a factor IX and a protein C deficiency in a young child who presented, according to the bleeding tendency, as a hemophilia B patient in this particular hemophiliac, baseline prothrombin fragment F1+2 levels were unexpectedly elevated and increased after an injection of a very high purity factor IX concentrate. This observation raised a question regarding the substitution schedule in the case of repeated injections of factor IX, since the thrombotic tendency has been a major concern with some factor IX concentrates. We monitored factor IX, prothrombin fragment F1+2 and D‐dimer plasma levels before and during the 6 hr following the injection of an immunopurified factor IX concentrate. The results showed an increase in the F1+2 levels after the factor IX injection, but an increase lower than previously observed with an ion‐exchange chromatography‐purified concentrate. Furthermore the F1+2 level returned to baseline value 6 hr after administration. This factor IX concentrate seems to be best for use in the patient where repeated injections are involved (as employed during surgery). Moreover, the data point out the advantage of a monoclonal antibody‐purified factor IX concentrate over less purified concentrates in a specific situation, with regard to the thrombogenic risk.
Spectrum of β‐thalassemia mutations in Calabria: Implications for prenatal diagnosis
Authors: Magro Saverio , Santilli Emanuele , Mancuso Rita , Puzzonia Pasquale , Consarino Caterina , Morgione Sergio , Galati Maria Concetta , Fersini Giuseppina , Madonna Giovanna , Brancati Carmela , Vadalà Pasquale , Molica Stefano
Published: November 2012

Using a combination of oligonucleotide probes and restriction endonuclease enzymes, we characterize β‐thalassemic mutations in 91 homozygous patients and 86 unrelated carriers. Overall, 268 β‐thalassemic genes were obtained. Eleven β‐globin mutations were identified, confirming the wide molecular heterogeneity of β‐thalassemia in Calabria. Information from the present study represents the mainstay for the development of a program of early prenatal diagnosis by direct detection of mutations in Calabria.
Synthesis of star polymer poly(ethylene glycol)3–poly(N,N‐dimethyl acrylamide) and its application in protein resistance and separation
Authors: Xing Jinxing , Tan Lin , Cao Fuhu , Wang Yanmei
Published: November 2012

A star polymer composed of three poly(ethylene glycol) (PEG) arms and one poly(N,N‐dimethyl acrylamide) (PDMA) arm (PEG3–PDMA) was synthesized by amidation and atom‐transfer radical polymerization. The structure of PEG3–PDMA was confirmed by 1H‐NMR and gel permeation chromatography results. The surface adsorption and protein‐resistance behaviors of the star polymer PEG3–PDMA, diblock copolymer PEG–PDMA, and homopolymer PEG were investigated by a quartz crystal microbalance with dissipation. The results indicate that the PEG3–PDMA coating could reduce protein adsorption to 13% at least, more effectively than the PEG–PDMA coating; this indicated that the protein‐resistance properties depended on the PEG chain density and surface coverage. If PEG3–PDMA were to be used as the physical coating in capillary zone electrophoresis, it could yield a well‐suppressed eletroosmotic flow with greater stability and separate proteins with a lower relative standard deviration (RSD) of protein migration time and a higher separation efficiency than a bare fused‐silica capillary in a broad pH range. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Poly (diallyldimethylammoniumchloride)/sodium‐montmorillonite composite; structure, and adsorption properties
Authors: Gunister Ebru , Bozkurt Ayse Muge , Catalgil‐Giz Huceste
Published: November 2012

A cationic polyelectrolyte, poly (diallyldimethylammoniumchloride) (PDADMAC) and a smectite‐type layered silicate (sodium activated montmorillonite clay (Sodium‐Montmorillonite, NaMt)), intercalated composites (PDADMAC/NaMt) were prepared. Basal spacings (d001) of NaMt in composites were measured by X‐Ray diffraction analysis (XRD). Ultrasonic addition of low molecular weight PDADMAC into the NaMt structure (at very low concentration and very low PDADMAC(g)/NaMt(g) ratios) resulted in good adsorbing properties both for positively and negatively charged dyes. The adsorption kinetics of the prepared composites both for negatively charged [remazol black (RB)] and positively charged [methylene blue (MB)] reactive dyes were investigated. The RB adsorption efficiency of the positively charged composite is approximately three times that of the pure NaMt while its MB adsorption efficiency is as good as that of pure NaMt. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Fluorescent polymer with CdTe quantum dots and 1,8‐naphthahmide fluorescent polymer: Synthesis, characterization, and FRET
Authors: Huang Weiyun , Li Lichao , Hui Guodong , Chen Deben , Zhong Anyong
Published: November 2012

In this paper, we reported a new method to fabricate CdTe quantum dots (CdTe QDs), which were synthesized in aqueous solution using thioglycolic acid and L‐phenylalanine (L‐Phe) as costabilizing agent. Then, they were transferred into organic phase with the assistance of cetyltrimethylammonium bromide (CTAB) for further utilization. Finally, we use toluene diisocyanate as a bridge between CdTe QDs and polyacrylate (CPA), whose side chain has hydroxyl group, to synthesize a fluorescent composite polymer CdTe‐CPA. In addition, we synthesized an organic substance 4‐[2,4‐di(tert‐butyl)]phenoxy‐N‐(2‐hydroxyethyl)‐1,8‐naphthalimide (N), and obtained 1,8‐naphthahmide fluorescent polymer N‐CPA in the same way as it did on CdTe‐CPA. The resulting materials were characterized by Fourier transform infrared spectroscopy (FT‐IR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), transmission electron microscope (TEM), and photoluminescence (PL). Then, we studied the fluorescence resonance energy transfer (FRET) between CdTe‐CPA and N‐CPA. The data obtained from absorption and fluorescence emission spectral indicated that the FRET from N‐CPA to CdTe‐CPA could be efficiently triggered in the solution of chloroform. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Acetone‐Induced Graphene Oxide Film Formation at the Water–Air Interface
Authors: Wei Li , Chen Fuming , Wang Hong , Zeng Tingying Helen , Wang Qiusheng , Chen Yuan
Published: November 2012

Graphene oxide (GO) is an amphiphilic soft material, which can accumulate at the water–air interface. However, GO sheets diffuse slowly in the aqueous phase because of their large size. It is still challenging to form high quality GO films in a controllable and simple way. In this study, we showed that GO sheets can quickly migrate to the water–air interface and form thin films when a suitable amount of acetone is directly mixed with a GO aqueous dispersion. The film formation rate and surface coverage of GO sheets depend on the volume of acetone added, GO dispersion concentration, and formation time. Among several organic solvents, acetone has its advantage for GO film formation owing to its three properties: a nonsolvent to GO aqueous dispersions, miscible with a GO aqueous dispersion, and fast evaporation. Furthermore, we have found that the film formation also is governed by the size of GO sheets and their oxygen content. Although smaller GO sheets could migrate to the water–air interface faster, the overlapping of small GO sheets and the increase in contact resistance is not desirable. A higher oxygen content in GO sheets could also result in smaller GO sheets. Multilayer GO films can be obtained through layer‐by‐layer dip‐coating. These findings open opportunities in developing simple scalable GO film fabrication processes.
Age‐dependent magnetosensitivity of heart muscle ouabain receptors
Authors: Narinyan Lilia Yu , Ayrapetyan Gayane S. , Ayrapetyan Sinerik N.
Published: November 2012

In our previous work we have shown that the age‐dependent decrease in the magnetosensitivity of heart muscle hydration is accompanied by a dysfunction of the Na+/K+ pump. The reciprocal relation between the Na+/K+ pump and Na+/Ca2+ exchange in development was suggested as a possible pathway for the age‐dependent decrease in the magnetosensitivity of heart muscle hydration (water content). Because high and low affinity ouabain receptors in cell membranes are involved in Na+/Ca2+ exchange and Na+/K+ pump functions, respectively, the effect of a 0.2 T static magnetic field (SMF) on dose‐dependent, ouabain‐induced hydration and [3H]‐ouabain binding with heart muscle tissues in young, adult and older rats was studied. Three populations of receptors in membranes with high (10−11–10−9 M), middle (10−9–10−7 M) and low (10−7–10−4 M) affinity to [3H]‐ouabain were distinguished, which had specific dose‐dependent [3H]‐ouabain binding kinetics and effects on muscle hydration. The magnetosensitivity of [3H]‐ouabain binding kinetics with high affinity receptors was prominent in all the three age groups of animals, while with low affinity receptors it was more expressed only in the young group of animals. All three types of receptors that caused modulations of muscle hydration were age dependent and magnetosensitive. Based on the obtained data we came to the conclusion that heart muscle hydration in young animals is more magnetosensitive due to the intense expression of high affinity ouabain receptors, which declines with aging. Bioelectromagnetics 34:312–322, 2013. © 2012 Wiley Periodicals, Inc.
Empathy in Forensic Evaluations: a Systematic Reconsideration
Authors: Brodsky Stanley L. , Wilson Jennifer Kelly
Published: November 2012

This paper reexamines the Shuman seminal paper arguing against empathic behaviors in forensic evaluations. Shuman concluded that empathy by examiners seduces evaluees into believing a therapeutic relationship exists. We reconsider empathy as an element of rapport and a helpful supplement in a successful assessment. Actively avoiding empathy could lead to cold and callous examiner self‐presentation, which may in turn produce biased and negative results. In this paper we assert that ethical forensic professionals may use moderate empathy during an assessment. Examiners should consider it not as a component of subjectivity and pseudotherapy, but rather as a potentially useful tool for effective assessments. Copyright © 2012 John Wiley & Sons, Ltd.
Macrocyclization of Organo‐Peptide Hybrids through a Dual Bio‐orthogonal Ligation: Insights from Structure–Reactivity Studies
Authors: Frost John R. , Vitali Francesca , Jacob Nicholas T. , Brown Micah D. , Fasan Rudi
Published: November 2012

Macrocycles constitute an attractive structural class of molecules for targeting biomolecular interfaces with high affinity and specificity. Here, we report systematic studies aimed at exploring the scope and mechanism of a novel chemo‐biosynthetic strategy for generating macrocyclic organo‐peptide hybrids (MOrPHs) through a dual oxime‐/intein‐mediated ligation reaction between a recombinant precursor protein and bifunctional, oxyamino/1,3‐amino‐thiol compounds. An efficient synthetic route was developed to access structurally different synthetic precursors incorporating a 2‐amino‐ mercaptomethyl‐aryl (AMA) moiety previously found to be important for macrocyclization. With these compounds, the impact of the synthetic precursor scaffold and of designed mutations within the genetically encoded precursor peptide sequence on macrocyclization efficiency was investigated. Importantly, the desired MOrPHs were obtained as the only product from all the different synthetic precursors probed in this study and across peptide sequences comprising four to 15 amino acids. Systematic mutagenesis of the “i−1” site at the junction between the target peptide sequence and the intein moiety revealed that the majority of the 20 amino acids are compatible with MOrPH formation; this enables the identification of the most and the least favorable residues for this critical position. Furthermore, interesting trends with respect to the positional effect of conformationally constrained (Pro) and flexible (Gly) residues on the reactivity of randomized hexamer peptide sequences were observed. Finally, mechanistic investigations enabled the relative contributions of the two distinct pathways (side‐chain→C‐end ligation versus C‐end→side‐chain ligation) to the macrocyclization process to be dissected. Altogether, these studies demonstrate the versatility and robustness of the methodology to enable the synthesis and diversification of a new class of organo‐peptide macrocycles and provide valuable structure–reactivity insights to inform the construction of macrocycle libraries through this chemo‐biosynthetic strategy.
A Pan Photoaffinity Probe for Detecting Active Forms of Matrix Metalloproteinases
Authors: Nury Catherine , Czarny Bertrand , Cassar‐Lajeunesse Evelyne , Georgiadis Dimitris , Bregant Sarah , Dive Vincent
Published: November 2012

A photoaffinity probe based on the scaffold of a potent broad‐spectrum phosphinic peptide inhibitor of matrix metalloproteinases (MMPs) has been developed. A photolabile diazirine group for covalent modification of MMP active forms was incorporated at the P1′ position, and a tritium radioactive label for the sensitive detection of MMP covalent adducts by radioimaging was attached. The probe was characterized on seven catalytic domains of human MMPs (MMP‐2, ‐3, ‐8, ‐9, ‐12, ‐13 and ‐14) and was found to display nanomolar affinities towards this set of MMPs, covalently modifying them with crosslinking yields varying from 12 to 58 %, thus leading to highly sensitive detection of these MMPs. In a complex proteome complemented with four recombinant MMPs (MMP‐2, ‐9, ‐12 and ‐13), this probe enabled their simultaneous detection with a threshold of few femtomoles and low background labelling. Those properties should make this new pan‐activity‐based MMP probe a valuable tool for the detection of MMP active forms from biological fluids or tissue extracts.
Synthesis of Thermally Stable Energetic 1,2,3‐Triazole Derivatives
Authors: Kumar A. Sudheer , Ghule Vikas D. , Subrahmanyam S. , Sahoo Akhila K.
Published: November 2012

Various thermally stable energetic polynitro‐aryl‐1,2,3‐triazoles have been synthesized through Cu‐catalyzed [3+2] cycloaddition reactions between their corresponding azides and alkynes, followed by nitration. These compounds were characterized by analytical and spectroscopic methods and the solid‐state structures of most of these compounds have been determined by using X‐ray diffraction techniques. Most of the polynitro‐bearing triazole derivatives decomposed within the range 142–319 °C and their heats of formation and crystal densities were determined from computational studies. By using the Kamlet–Jacobs empirical relation, their detonation velocities and pressures were calculated from their heats of formation and crystal densities. Most of these newly synthesized compounds exhibited high positive heats of formation, good thermal stabilities, reasonable densities, and acceptable detonation properties that were comparable to those of TNT.
Bioengineering Parameters for Single‐Use Bioreactors: Overview and Evaluation of Suitable Methods
Authors: Löffelholz Christian , Husemann Ute , Greller Gerhard , Meusel Wolfram , Kauling Jörg , Ay Peter , Kraume Matthias , Eibl Regine , Eibl Dieter
Published: November 2012

During the past five years, the number of single‐use bioreactors used in biopharmaceutical research and production has increased tremendously. This increase has been particularly associated with mammalian cell culture processes from small‐ to medium‐scale volumes. Even though nowadays customers can choose from a multitude of 2nd and 3rd generation single‐use bioreactors, ranging from mL‐ up to m3‐scale, there is a lack of knowledge of their engineering parameters. Different approaches have been applied to characterization investigations, resulting in an inability to compare different single‐use bioreactors with each other and their reusable counterparts, creating an obstacle to a systematic approach to scaling‐up the process. This article describes parametric, experimental and computer‐based numeric methods for biochemical engineering characterization of single‐use bioreactors, which have already been used successfully for the characterization of their reusable counterparts. For the first time, these methods have been evaluated in terms of their practical application.
Highly Ligand Efficient and Selective N‐2‐(Thioethyl)picolinamide Histone Deacetylase Inhibitors Inspired by the Natural Product Psammaplin A
Authors: Baud Matthias G. J. , Haus Patricia , Leiser Thomas , Meyer‐Almes Franz‐Josef , Fuchter Matthew J.
Published: November 2012

Novel picolinamide‐based histone deacetylase (HDAC) inhibitors were developed, drawing inspiration from the natural product psammaplin A. We found that the HDAC potency and isoform selectivity provided by the oxime unit of psammaplin A could be reproduced by using carefully chosen heterocyclic frameworks. The resulting (hetero)aromatic amide based compounds displayed very high potency and isoform selectivity among the HDAC family, in addition to excellent ligand efficiency relative to previously reported HDAC inhibitors. In particular, the high HDAC1 isoform selectivity provided by the chloropyridine motif represents a valuable design criterion for the development of new lead compounds and chemical probes that target HDAC1.
Long‐term regional control and survival in patients with “low‐risk,” early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation
Authors: Ganly Ian , Goldstein David , Carlson Diane L. , Patel Snehal G. , O'Sullivan Brian , Lee Nancy , Gullane Patrick , Shah Jatin P.
Published: November 2012

BACKGROUND:

The objectives of this study were to determine the incidence of locoregional failure in patients with low‐risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation.

METHODS:

A combined database of patients with OTSCC who received treatment at Memorial Sloan‐Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1‐T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient‐related, tumor‐related, and treatment‐related characteristics were recorded. Local recurrence‐free survival, regional recurrence‐free survival, and disease‐specific survival were calculated by the Kaplan‐Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis.

RESULTS:

At a median follow‐up of 66 months (range 1‐171 months), the 5‐year rates of local recurrence‐free survival, regional recurrence‐free survival, and disease‐specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence‐free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease‐specific survival compared with those who did not (33% vs 97%; P < .0001).

CONCLUSIONS:

Patients with low‐risk, pathologic T1‐T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥4 mm thick. Cancer 2013. © 2013 American Cancer Society.
Effect of including cancer‐specific variables on models examining short‐term outcomes
Authors: Merkow Ryan P. , Kmiecik Thomas E. , Bentrem David J. , Winchester David P. , Stewart Andrew K. , Ko Clifford Y. , Bilimoria Karl Y.
Published: November 2012

BACKGROUND:

The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) generally has not collected cancer‐specific variables. Because increasing numbers of studies are using ACS NSQIP data to study cancer surgery, the objectives of the current study were 1) to examine differences between existing ACS NSQIP variables and cancer registry variables, and 2) to determine whether the addition of cancer‐specific variables improves modeling of short‐term outcomes.

METHODS:

Data from patients in the ACS NSQIP and National Cancer Data Base (NCDB) who underwent colorectal resection for cancer were linked (2006‐2008). By using regression methods, the relative importance of cancer staging and neoadjuvant therapy variables were assessed along with their effects on morbidity, serious morbidity, and mortality.

RESULTS:

From 146 hospitals, 11,405 patients were identified who underwent surgery for colorectal cancer (colon, 85%; rectum, 15%). The NCDB metastatic cancer variable and the ACS NSQIP disseminated cancer variables agreed marginally (Cohen kappa coefficient, 0.454). For mortality, only the ACS NSQIP disseminated cancer variable and the NCDB stage IV variable were identified as important predictors; whereas the variables stage I through III, tumor (T)‐classification, and lymph node (N)‐classification were not selected. Cancer stage variables were inconsistently important for serious morbidity (stage IV, T‐classification), superficial surgical site infection (N‐classification), venous thromboembolism (metastatic cancer), and pneumonia (T‐classification). With respect to neoadjuvant therapy, ACS NSQIP and NCDB variables agreed moderately (kappa, 0.570) and predicted superficial surgical site infection, serious morbidity, and organ space surgical site infection. The model fit was similar regardless of the inclusion of stage and neoadjuvant therapy variables.

CONCLUSIONS:

Although advanced disease stage and neoadjuvant therapy variables were predictors of short‐term outcomes, their inclusion did not improve the models. Cancer 2013. © 2012 American Cancer Society.
Evidence for a regional specificity in the density and distribution of noradrenergic varicosities in rat cortex
Authors: Agster Kara L. , Mejias‐Aponte Carlos A. , Clark Brian D. , Waterhouse Barry D.
Published: November 2012

The brainstem nucleus locus coeruleus (LC) is the sole source of norepinephrine (NE)‐containing fibers in the mammalian cortex. Previous studies suggest that the density of noradrenergic fibers in rat is relatively uniform across cortical regions and that cells in the nucleus discharge en masse. This implies that activation of the LC results in equivalent release of NE throughout the cortex. However, it is possible that there could be differences in the density of axonal varicosities across regions, and that these differences, rather than a difference in fiber density, may contribute to the regulation of NE efflux. Quantification of dopamine β‐hydroxylase (DβH)‐immunostained varicosities was performed on several cortical regions and in the ventral posterior medial (VPM) thalamus by using unbiased sampling methods. The density of DβH varicosities is greater in the prefrontal cortex than in motor, somatosensory, or piriform cortices, greater in superficial than in deep layers of cortex, and greater in the VPM than in the somatosensory cortex. Our results provide anatomical evidence for non‐uniform release of NE across functionally discrete cortical regions. This morphology may account for a differential, region‐specific, impact of LC output on different cortical areas. J. Comp. Neurol. 521:2195–2207, 2013. © 2012 Wiley Periodicals, Inc.
Diversity of thalamorecipient spine morphology in cat visual cortex and its implication for synaptic plasticity
Authors: da Costa Nuno Maçarico
Published: November 2012

A feature of spine synapses is the existence of a neck connecting the synapse on the spine head to the dendritic shaft. As with a cable, spine neck resistance (Rneck) increases with increasing neck length and is inversely proportional to the cross‐sectional area of the neck. A synaptic current entering a spine with a high Rneck will lead to greater local depolarization in the spine head than would a similar input applied to a spine with a lower Rneck. This could make spines with high Rneck more sensitive to plastic changes since voltage sensitive conductances, such as N‐methyl‐D‐aspartic acid (NMDA) channels can be more easily activated. This hypothesis was tested using serial section electron microscopic reconstructions of thalamocortical spine synapses and spine necks located on spiny stellate cells and corticothalamic cells from area 17 of cats. Thalamic axons and corticothalamic neurons were labeled by injections of the tracer biotinylated dextran amine (BDA) in the dorsal lateral geniculate nucleus (dLGN) of anesthetized cats and spiny stellates were filled intracellularly in vivo with horseradish peroxidase. Twenty‐eight labeled spines that formed synapses with dLGN boutons were collected from three spiny stellate and four corticothalamic cells and reconstructed in 3D from serial electron micrographs. Spine length, spine diameter, and the area of the postsynaptic density were measured from the 3D reconstructions and Rneck of the spine was estimated. No correlation was found between the postsynaptic density size and the estimated spine Rneck. This suggests that forms of plasticity that lead to larger synapses are independent of spine neck resistance. J. Comp. Neurol. 521:2058–2066, 2013. © 2012 Wiley Periodicals, Inc.
Membrane microdomain organization, calcium signal, and NFAT activation as an important axis in polarized Th cell function
Authors: Izsepi Emese , Himer Leonora , Szilagyi Orsolya , Hajdu Peter , Panyi György , Laszlo Gloria , Matko Janos
Published: November 2012

T helper lymphocytes become polarized upon antigen and cytokine stimuli received after their maturation in the thymus. Since the balance of Th1 and Th2 responses is critical in healthy and pathological immune responses, understanding the molecular base of T cell polarization still remained an important question. Using our Th0/Th1/Th2 hybridoma model system, we performed a comparative study on polarized Th1 and Th2 cells in terms of their membrane raft expression/composition, their TCR mediated activation signaling, and sensitivity to activation‐induced cell death (AICD) using flow and image cytometric methods. We show here that the TCR stimulation induced more intense and sustained Ca2+‐response in Th1 cells compared to Th2 ones correlates well with a shorter nuclear residence time of the Ca2+‐dependent NFAT transcription factor in Th2 cells. In addition, NFAT translocation directly depended on lipid raft integrity/membrane cholesterol level. Expression pattern of raftophilic accessory proteins (CD4, CD59, and CD48) and lipids (GM1, cholesterol) were also different in the Th1 and Th2 hybridomas, similarly to differentiated spleen Th cells. The activation‐induced, remarkably clustered and polarized membrane distribution of TCR/CD3 complex in Th1, but not in Th2 cells, together with an increased raft localization of Kv1.3 ion channels regulating the Ca2+‐response, are consistent with the above properties of NFAT. Finally, the polarized Th cells, especially Th1, were more sensitive to AICD than their unpolarized Th0 precursor. These results suggest that the membrane microdomain organization—Ca2+‐signaling—NFAT activation axis is an important determinant of polarized Th cell effector function and fate. © 2012 International Society for Advancement of Cytometry
A Technique to Increase Accessibility to Late‐Stage Chick Embryos for In Ovo Manipulations
Authors: Spurlin James , Lwigale Peter
Published: November 2012

Background: During early development, avian embryos are easily accessible in ovo for transplantations and experimental perturbations. However, these qualities of the avian embryonic model rapidly wane shortly after embryonic day (E)4 when the embryo is obscured by extraembryonic membranes, making it difficult to study developmental events that occur at later stages in vivo. Results: In this study, we describe a multistep method that involves initially windowing eggs at E3, followed by dissecting away extraembryonic membranes at E5 to facilitate embryo accessibility in ovo until later stages of development. The majority of the embryos subjected to this technique remain exposed between E5 and E8, then become gradually displaced by the growing allantois from posterior to anterior regions. Conclusions: Exposed embryos are viable and compatible with embryological and modern developmental biology techniques including tissue grafting and ablation, gene manipulation by electroporation, and protein expression. This technique opens up new avenues for studying complex cellular interactions during organogenesis and can be further extrapolated to regeneration and stem cell studies. Developmental Dynamics 242:148–154, 2013. © 2012 Wiley Periodicals, Inc.
Nanoparticles Based Electroanalysis in Diagnostics Applications
Authors: Merkoçi Arben
Published: November 2012

Nanoparticles with electrochemical properties such as red‐ox changes easy to be followed by stripping analysis or electrocatalysis to be followed by simple amperometric detection represent interesting building blocks in the design and fabrication of novel biosensors with interest for diagnostics applications. Various examples related to DNA, protein and cell detection are shown. Nanoparticles are mostly used as labels in a similar way as enzymes or dyes but offering the advantages of better stability and in general cost efficiency of the devices. The employment of nanoparticles in electrochemical based biosensing systems is simple and the obtained performance seems to fit with the requirements for real applications in detection of various biomarkers with interest for point of care applications and even early detection or during treatment of illnesses such as cancer, beside others.
Amperometric Magnetoimmunosensors for Direct Determination of D‐Dimer in Human Serum
Authors: Gamella María , Campuzano Susana , Conzuelo Felipe , Reviejo A. Julio , Pingarrón José M.
Published: November 2012

Two different D‐dimer disposable amperometric immunosensing designs based on indirect competitive or sandwich formats and the use of carboxylic acid‐modified magnetic beads (COOH‐MBs) and screen‐printed carbon electrodes (SPCEs) have been developed and compared. In both approaches, the resulting modified MBs were magnetically captured on the surface of a SPCE which was used as the transducer for the electrochemical detection at −0.20 V upon addition of H2O2, and hydroquinone (HQ). Both configurations exhibited linear ranges of clinical usefulness and detection limits quite below the clinical threshold (0.5 µg mL−1 D‐dimer). The sandwich configuration has been successfully tested with serum samples.
Holocene profile changes along a California coastal stream
Authors: Haible William W.
Published: November 2012

Walker Creek in Marin County, California is a coastal stream draining to Tomales Bay, which lies in the San Andreas Rift Zone. Its valley contains an alluvial fill with a basal gravel dated at 5000 years BP. In upstream parts of the watershed, channels are incised arroyo‐like in the fill leaving the valley floor standing as a high terrace averaging 5·5 m (18 ft) high. Below this terrace is an inner terrace of historic age that stands 2·4 m (8 ft) above the streambed. The stratigraphy and morphology of this valley are seen in others nearby, and indicate that in the last half of Holocene time in this region a single episode of valley alluviation was followed by two episodes of valley cutting.

The second episode of valley cutting is occurring in the present time. During the last 60 years the flow has become seasonal, the stream has incised 1·5 m (5 ft) below the inner terrace in upstream reaches, aggraded 1·2 m (4 ft) in downstream reaches, and extended its estuary. Incision upstream has begun to re‐expose the bedrock valley floor and is associated with aggradation downstream that has caused the flood plain to overtop both terraces. This has decreased the stream's gradient.

Using a stream that is currently effecting major changes in its valley and channel morphology, two aspects of hydraulic adjustment in fluvial systems are examined. The changes in the average slope of the longitudinal profile are small but measureable. Profile concavity has not changed measurably. The various profiles that have existed in Holocene time show that stream gradient can be, but is not necessarily, slightly adjusted during valley filling and cutting. Flow measurements at a high discharge show that the channel has begun to assume the hydraulic geometry of an ephemeral channel. Adjustments of depth, velocity, and roughness appear to be hydraulic adjustments in response to changing watershed conditions.
Dementia case management and risk of long‐term care placement: a systematic review and meta‐analysis
Authors: Tam‐Tham Helen , Cepoiu‐Martin Monica , Ronksley Paul E. , Maxwell Colleen J. , Hemmelgarn Brenda R.
Published: November 2012

Objectives

The objective of our study is to evaluate the effectiveness of dementia case management compared with usual care on reducing long‐term care placement, hospitalization, and emergency department visits for adult patients with dementia. We also sought to evaluate the effectiveness of this intervention on delaying time to long‐term care placement and hospitalization.

Methods

We searched electronic databases supplemented by bibliographies and conference proceedings for randomized controlled trials testing the effectiveness of dementia case management in reducing resource utilization in a population of caregiver–care recipient dyads living in the community. We meta‐analyzed the risk ratio (RR) and weighted mean differences of long‐term care placement and the RR of hospital admissions. Pooled estimates were further stratified by study characteristics and measures of study quality.

Results

Seventeen studies were included in the meta‐analysis. The overall pooled RR of long‐term care placement was 0.94 (95% confidence interval [0.85, 1.03]; p = 0.227) for dementia case management compared with usual care. Stratification by follow‐up duration indicated a statistically significant reduction in risk of long‐term care placement when follow‐up duration was less than 18 months (RR 0.61, 95% confidence interval [0.41, 0.91], p = 0.015). There was no effect of dementia case management compared with usual care for the other outcomes.

Conclusion

Dementia case management demonstrated a short‐term positive effect on reducing the risk of long‐term care placement among older people with dementia residing in the community. However, other sources of resource utilization and more extended effects of dementia case management on risk of long‐term care placement warrant further investigation. Copyright © 2012 John Wiley & Sons, Ltd.
Concurrent and Longitudinal Relationships Between Development in Graphic, Language and Symbolic Play Domains from the Fourth to the Fifth Year
Authors: Kirkham Julie , Stewart Andrew , Kidd Evan
Published: November 2012

This research investigated the developing inter‐relationships between language, graphic symbolism and symbolic play both concurrently and longitudinally from the fourth to the fifth year of childhood. Sixty children (n = 60) aged between 3 and 4 years completed multiple assessments of language and assessments of graphic symbolism, symbolic play and non‐verbal intelligence. A year later, 31 children (n = 31) were re‐tested using the same assessments. The findings revealed that skills within each symbolic domain were inter‐related during the fourth year, appearing to develop in a domain‐general type fashion based upon a common underlying symbolic mechanism. However, between the fourth and the fifth years, only language had predictive validity, suggesting a shift towards the verbal mediation of symbolic play and graphic symbolism as language becomes progressively internalized (Vygotsky, 1962, 1978). Copyright © 2012 John Wiley & Sons, Ltd.
miQ—A novel microRNA based diagnostic and prognostic tool for prostate cancer
Authors: Larne Olivia , Martens‐Uzunova Elena , Hagman Zandra , Edsjö Anders , Lippolis Giuseppe , den Berg Mirella S. Vredenbregt‐van , Bjartell Anders , Jenster Guido , Ceder Yvonne
Published: November 2012

Today, the majority of prostate tumors are detected at early stages with uncertain prognosis. Therefore, we set out to identify early predictive markers of prostate cancer with aggressive progression characteristics. We measured the expression of microRNAs (miRNA) using qRT‐PCR in formalin fixed and paraffin embedded prostatic tissue samples from a Swedish cohort of 49 patients with prostate cancer and 25 without cancer and found seven of 13 preselected miRNAs to discriminate between the two groups. Subsequently, four discriminatory miRNAs were combined to a quota, denoted the miRNA index quote (miQ); ((miR‐96‐5p × miR‐183‐5p)/(miR‐145‐5p × miR221‐5p)). The advantage of using a quote is increased discrimination, no need for house‐keepings, and most important it may be an advantage considering the heterogeneity of the disease. miQ was found to successfully predict diagnosis (p < 0.0001) with high accuracy (area under the curve, AUC = 0.931) that was verified in an independent Dutch cohort and three external cohorts, and significantly outperforming prostate‐specific antigen. Importantly, miQ also has prognostic power to predict aggressiveness of tumors (AUC = 0.895), metastatic statues (AUC = 0.827) and overall survival (p = 0.0013, Wilcoxon test HR = 6.5, median survival 2 vs. 5 years), verified in the Dutch cohort. In this preliminary study, we propose that miQ has potential to be used as a clinical tool for prostate cancer diagnosis and as a prognostic marker of disease progression.
Differential effect of visual and gustatory stimuli on experimental jaw muscle pain
Authors: Horjales‐Araujo E. , Finnerup N.B. , Jensen T.S. , Svensson P.
Published: November 2012

Background

Emotions form an important component in the expression and manifestation of pain. This study tested whether emotionally loaded visual and gustatory conditioning stimuli could influence experimental jaw muscle pain.

Patients and Methods

Thirty‐one healthy subjects participated in this study. In two sessions, experimental jaw muscle pain was evoked by injection of hypertonic saline (HS) into the masseter muscle. In the first session, jaw muscle pain was conditioned by positive, negative or neutral pictures. In the next session, jaw muscle pain was conditioned by sweet, bitter or tasteless gelatine in the mouth. The subjects continuously rated pain intensity as well as mood and unpleasantness/pleasantness of the conditioning stimuli. As a control experiment, the same design was applied in eight subjects using painful thermal stimuli.

Results

HSevoked moderate levels of pain in all subjects. During conditioning with negatively loaded pictures,HS‐evoked pain was higher compared with neutral and positive pictures (p = 0.002). There was a significant correlation between negative emotional scores linked to the pictures andHS‐evoked pain intensity (r = 0.404,p = 0.021). No effects onHS‐evoked pain intensity were observed during positive pictures or during sweet or bitter gustatory stimuli. The latter may be due to failure of the gustatory stimuli to generate changes in emotional scores. No significant effects were observed on thermal pain sensitivity.

Conclusion

These results suggest that not all conditioning stimuli are potent modifiers of emotions, which seems to be a prerequisite for effects on muscle pain perception.
Robocasting nanocomposite scaffolds of poly(caprolactone)/hydroxyapatite incorporating modified carbon nanotubes for hard tissue reconstruction
Authors: Dorj Biligzaya , Won Jong‐Eun , Kim Joong‐Hyun , Choi Seong‐Jun , Shin Ueon Sang , Kim Hae‐Won
Published: November 2012

Nanocomposite scaffolds with tailored 3D pore configuration are promising candidates for the reconstruction of bone. Here we fabricated novel nanocomposite bone scaffolds through robocasting. Poly(caprolactone) (PCL)—hydroxyapatite (HA) slurry containing ionically modified carbon nanotubes (imCNTs) was robotic‐dispensed and structured layer‐by‐layer into macrochanneled 3D scaffolds under adjusted processing conditions. Homogeneous dispersion ofimCNTs (0.2 wt % relative to PCL‐HA) was achieved in acetone, aiding in the preparation of PCL‐HA‐imCNTs slurry with good mixing property. Incorporation ofimCNTs into PCL‐HA composition significantly improved the compressive strength and elastic modulus of the robotic‐dispensed scaffolds (∼1.5‐fold in strength and ∼2.5‐fold in elastic modulus). When incubated in simulated body fluid (SBF), PCL‐HA‐imCNT nanocomposite scaffold induced substantial mineralization of apatite in a similar manner to the PCL‐HA scaffold, which was contrasted in pure PCL scaffold. MC3T3‐E1 cell culture on the scaffolds demonstrated that cell proliferation levels were significantly higher in both PCL‐HA‐imCNT and PCL‐HA than in pure PCL, and no significant difference was found between the nanocomposite scaffolds. When the PCL‐HA‐imCNT scaffold was implanted into a rat subcutaneous tissue for 4 weeks, soft fibrous tissues with neo‐blood vessels formed well in the pore channels of the scaffolds without any significant inflammatory signs. Tissue reactions in PCL‐HA‐imCNT scaffold were similar to those in PCL‐HA scaffold, suggesting incorporatedimCNT did not negate the beneficial biological roles of HA. While more long‐termin vivoresearch in bone defect models is needed to confirm clinical availability, our results suggest robotic‐dispensed PCL‐HA‐imCNT nanocomposite scaffolds can be considered promising new candidate matrices for bone regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Particle size modeling and morphology study of chitosan/gelatin/nanohydroxyapatite nanocomposite microspheres for bone tissue engineering
Authors: Bagheri‐Khoulenjani Shadab , Mirzadeh Hamid , Etrati‐Khosroshahi Mohammad , Ali Shokrgozar Mohammad
Published: November 2012

In this study, nanocomposite microspheres based on chitosan/gelatin/nanohydroxyapatite were fabricated, and effects of the nanohydroxyapatite/biopolymer (chitosan/gelatin) weight ratio (nHA/P), stirring rate, chitosan concentration and biopolymer concentration on the particle size, and morphology of nanocomposite microspheres were investigated. Particle size of microspheres was modeled by design of experiments using the surface response method. Particle size, morphology of microspheres, and distribution of nanoparticles within the composite microspheres were evaluated using an optical microscope, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. X‐ray diffraction and Fourier transform infrared spectroscopy were applied to study the physical and chemical characteristics of microspheres. Results showed that by modulating the nHA/P ratio, chitosan concentration, polymer concentration, and stirring rate, it is possible to fabricate microspheres in wide rages of particle size (5–150 μm). Analysis of variance confirmed that the modified quadratic model can be used to predict the particle size of nanocomposite microspheres within the design space. SEM studies showed that microspheres with different compositions had totally different morphologies from dense morphologies to porous ones. TEM images demonstrated that nanoparticles were distributed uniformly within the polymeric matrix. MTT assay and cell culture studies showed that microspheres with different compositions possessed good biocompatibility. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.