bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrostatic properties of confluent Caco‐2 cell layer correlates to their microvilli growth and determines underlying transcellular flow
Authors: Vandrangi P. , Lo D.D. , Kozaka R. , Ozaki N. , Carvajal N. , Rodgers V.G.J.
Published: April 2013

Recently, Rajapaksa et al. (2010) showed that the rate of uptake of potential vaccine delivery nanoparticles in the mucosal layer is a function of the electrostatic properties of the corresponding solvent. This fundamentally implies that the dominant driving forces that may be capitalized on for mucosal vaccine strategies are electrostatic in nature. We hypothesize that the driving force normal to the cell (in the direction from apical to basolateral across the cell) is of particular importance. In addition, it has been theoretically shown that the electrostatic properties of mucosal cells are directly related to their development of brush border. Here we correlate the development of brush border on a human mucosal epithelial model (Caco‐2) cultured in DMEM on 3.0 µm pore sized polycarbonate membranes to their corresponding electrostatic properties characterized by measuring their normal zeta potential. Properties of normal streaming potential, hydraulic permeability, and brush border development (as determined by size and number) were monitored for 2, 6, and 16 days (after cells were confluent). Human endothelial cells (HECs), which lack brush border, were used as the control. Our results demonstrate that normal zeta potential of Caco‐2 cells significantly changed from −5.7 ± 0.11 mV to −3.4 ± 0.11 mV for a period between 2 and 16 days, respectively. The zeta potential of the control cell line, HECs, stayed constant (statistically not different, P > 0.05) for the duration of the experiments. Our results show that the calculated increase in surface area of the Caco‐2 cells with microvilli from 6 to 16 days was directly proportional to the corresponding measured zeta potential difference. These results imply that microvilli alter the electrostatic local environment around Caco‐2 cells and, hence, enhance the normal electrostatic selective transport of solute across the mucosal barrier. Biotechnol. Bioeng. 2013;110: 2742–2748. © 2013 Wiley Periodicals, Inc.
Design, synthesis, and assessment of a de novo affinity adsorbent for the purification of recombinant human erythropoietin
Authors: El Khoury Graziella , Wang Yian , Wang Di , Jacob Shaleem I. , Lowe Christopher R.
Published: April 2013

This work describes the assessment of a de novo synthetic affinity ligand for recombinant human erythropoietin (rHuEPO), based on the multicomponent Ugi reaction. Four Ugi ligands were designed based on the X‐ray crystallographic structure of the complex between human erythropoietin and site 1 of its cell‐surface receptor (EPObp)2; screening of the ligands with pure rHuEPO samples identified a lead ligand (A9C10I8) immobilized on aldehyde‐functionalized agarose beads, which was able to bind and elute erythropoietin, as determined by SDS–PAGE and Western blot analyses. Furthermore, small‐scale affinity chromatography performed on the immobilized adsorbent showed its ability to isolate rHuEPO from a spiked mammalian cell supernatant with a purity of ∼80%, as estimated with gel densitometry. This approach could lead to the development of a cost‐effective downstream process for rHuEPO, as an alternative to the current multi‐step purification protocols. Biotechnol. Bioeng. 2013;110: 3063–3069. © 2013 Wiley Periodicals, Inc.
Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment
Authors: O'Neill J R , Stephens N A , Save V , Kamel H M , Phillips H A , Driscoll P J , Paterson-Brown S
Published: April 2013

Background

A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM.

Methods

This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival.

Results

A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1–0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009).

Conclusion

A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM.
An fMRI investigation of delay discounting in patients with schizophrenia
Authors: Avsar Kathy Burton , Weller Rosalyn Eve , Cox James Edward , Reid Meredith Amanda , White David Matthew , Lahti Adrienne Carol
Published: April 2013

Schizophrenia (SZ) is associated with a reduced ability to set meaningful goals to reach desired outcomes. The delay‐discounting (DD) task, in which one chooses between sooner smaller and later larger rewards, has proven useful in revealing executive function and reward deficits in various clinical groups. We used fMRI in patients with SZ and healthy controls (HC) to compare brain activation during performance of a DD task. Prior to the neuroimaging session, we obtained each participant's rate of DD, k, on a DD task and used it to select a version of the DD task for each participant's fMRI session. Because of the importance of comparing fMRI results from groups matched on performance, we used a criterion value of R2 > 0.60 for response consistency on the DD task to analyze fMRI activation to DD task versus control trials from consistent SZ (n = 14) and consistent HC (n = 14). We also compared activation between the groups on contrasts related to trial difficulty. Finally, we contrasted the inconsistent SZ (n = 9) with the consistent HC and consistent SZ; these results should be interpreted with caution because of inconsistent SZ's aberrant performance on the task. Compared with consistent HC, consistent SZ showed reduced activation to DD task versus control trials in executive function and reward areas. In contrast, consistent SZ showed more activation in the precuneus and posterior cingulate, regions of the default mode network (DMN) that are typically deactivated during tasks, and in the insula, a region linked to emotional processing. Furthermore, consistent SZ had abnormal activation of lateral and medial frontal regions in relation to trial difficulty. These results point to disruption of several neural networks during decision making, including the executive, reward, default mode, and emotional networks, and suggest processes that are impaired during decision making in schizophrenia.
Outcomes for balloon pulmonary valvuloplasty in adults: Comparison with a concurrent pediatric cohort
Authors: Taggart Nathaniel W. , Cetta Frank , Cabalka Allison K. , Hagler Donald J.
Published: April 2013

Objectives

To compare procedural outcomes of transcatheter balloon pulmonary valvuloplasty (BPV) in adults to a concurrent pediatric cohort and to identify whether BPV leads to improvement in symptoms among adults.

Background

BPV has long been utilized to relieve right ventricular outflow tract (RVOT) obstruction in neonates and young children. More recently, BPV has been performed in adults, but outcome data are limited in this population.

Methods

We reviewed all cases of BPV performed at Mayo Clinic's Congenital Cardiac Cath Lab from December 1993 to July 2012. Patients were excluded if they had additional congenital heart defects, other than simple left‐to‐right shunt lesions.

Results

89 children and 40 adults underwent 132 BPV procedures. Among the adults, 78% were symptomatic at the time of BPV. The most common symptoms were dyspnea and fatigue. RVOT systolic gradient was 42 ± 19 mmHg (children) and 54 ± 26 mmHg (adults) prior to BPV (P = 0.002). Adults experienced a greater reduction in gradient following BPV (32 ± 21 mmHg vs. 23 ± 19 mmHg; P = 0.007). No patients exhibited “suicide right ventricle” physiology after BPV. Among adults, mean follow‐up was 1.9 years (30 days–11 years). Symptoms improved in 20 of the 24 previously symptomatic adults for whom follow‐up data were available. Mean NYHA score improved from 2.2 to 1.4 following BPV. At last follow‐up, 52% of adults were free of any symptoms, a significant improvement from pre‐BPV (P = 0.0003). Only one patient described worsening of symptoms after BPV.

Conclusions

BPV is an effective procedure for symptomatic adults with pulmonary valve stenosis. In addition to immediate relief of RVOT gradient, adult patients may experience symptomatic improvement following BPV.© 2013 Wiley Periodicals, Inc.
Ultrasound‐Assisted Construction of Halogen‐Bonded Nanosized Cocrystals That Exhibit Thermosensitive Luminescence
Authors: Yan Dongpeng , Bučar Dejan‐Krešimir , Delori Amit , Patel Bhavnita , Lloyd Gareth O. , Jones William , Duan Xue
Published: April 2013

Multi‐component organic nanocrystals that are comprised of two or more supramolecular building blocks can be used to extend the design and assembly scope of solid molecular materials. Herein, we report the use of ultrasonication to prepare halogen‐bonded stilbene‐based nano‐cocrystals that exhibit different photoemission properties, including one‐ and two‐phonon emission and fluorescence lifetimes, relative to those of macrodimensional crystals. The structural transformation from nano‐cocrystals into nanocrystals upon heating results in a luminescence red‐shift from greenish blue to yellow. The temperature‐dependent ratiometric luminescence may allow such nano‐cocrystals to be used as fluorescent sensors and thermosensitive materials.
Synthesis of Fluorine‐Containing Multisubstituted Phenanthridines by Rhodium‐Catalyzed Alkyne [2+2+2] Cycloaddition and Tandem sp2 CH Difluoromethylenation
Authors: Li Yajun , Zhu Jiangtao , Zhang Lisi , Wu Yongming , Gong Yuefa
Published: April 2013

A highly efficient method for the synthesis of fluorine‐containing multisubstituted phenanthridines through Rh‐catalyzed alkyne [2+2+2] cycloaddition reactions has been developed. This method exhibits excellent functional‐group compatibility. When a bromodifluoromethyl group, rather than a trifluoromethyl group, was employed in the cycloaddition reaction, more‐complicated polycyclic compounds were obtained through tandem Rh‐catalyzed cycloaddition/CH difluoromethylenation. This route provides convenient access to fluorine‐containing polycyclic compounds.
Rare‐Earth‐Metal Dialkynyl Dimethyl Aluminates
Authors: Nieland Anja , Mix Andreas , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W.
Published: April 2013

A new class of rare‐earth‐metal alkynyl complexes has been prepared. The reactions of the tris(tetramethylaluminate)s of lanthanum, praseodymium, samarium, yttrium, holmium, and thulium, [Ln(AlMe4)3], with phenylacetylene afforded compounds [Ln{(μ‐CCPh)2AlMe2}3] (Ln=La (1), Pr (2), Sm (3), Y (4), Ho (5), Tm (6)). All of these compounds have been characterized by NMR spectroscopy, X‐ray crystallography, and by elemental analysis. NMR spectroscopic studies of the series of para‐ magnetic compounds [Ln(AlMe4)3] and [Ln{(μ‐CCPh)2AlMe2}3] have also been performed.
Mechanistic Insights into Copper‐Catalyzed Sonogashira–Hagihara‐Type Cross‐Coupling Reactions: Sub‐Mol % Catalyst Loadings and Ligand Effects
Authors: Zou Liang‐Hua , Johansson Adam Johannes , Zuidema Erik , Bolm Carsten
Published: April 2013

An efficient catalytic system for Sonogashira–Hagihara‐type reactions displaying ligand acceleration in the copper‐catalyzed formation of C(sp2)C(sp) bonds is described. The structure of the ligand plays a key role for the coupling efficiency. Various copper sources show excellent catalytic activity, even in sub‐mol % quantities. A wide variety of substituents is tolerated in the substrates. Mechanistic details have been revealed by kinetic measurements and DFT calculations.
Regional heterogeneity changes in DCE‐MRI as response to isolated limb perfusion in experimental soft‐tissue sarcomas
Authors: Alic L. , van Vliet M. , Wielopolski P. A. , ten Hagen T. L. M. , van Dijke C. F. , Niessen W. J. , Veenland J. F.
Published: April 2013

Experimental evidence supports an association between heterogeneity in tumor perfusion and response to chemotherapy/radiotherapy, disease progression and malignancy. Therefore, changes in tumor perfusion may be used to assess early effects of tumor treatment. However, evaluating changes in tumor perfusion during treatment is complicated by extensive changes in tumor type, size, shape and appearance. Therefore, this study assesses the regional heterogeneity of tumors by dynamic contrast‐enhanced MRI (DCE‐MRI) and evaluates changes in response to isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan. Data were acquired in an experimental cancer model, using a macromolecular contrast medium, albumin–(Gd–DTPA)45. Small fragments of BN 175 (a soft‐tissue sarcoma) were implanted in eight brown Norway rats. MRI of five drug‐treated and three sham‐treated rats was performed at baseline and 1 h after ILP intervention. Properly co‐registered baseline and follow‐up DCE‐MRI were used to estimate the volume transfer constant (Ktrans) pharmacokinetic maps. The regional heterogeneity was estimated in 16 tumor sectors and presented in cumulative map‐volume histograms. On average, ILP‐treated tumors showed a decrease in regional heterogeneity on the histograms. This study shows that heterogenic changes in regional tumor perfusion, estimated using DCE‐MRI pharmacokinetic maps, can be measured and used to assess the short‐term effects of a potentially curative treatment on the tumor microvasculature in an experimental soft‐tissue sarcoma model. Copyright © 2013 John Wiley & Sons, Ltd.
Radiolabeling approaches of nanoparticles with 99mTc
Authors: Psimadas Dimitrios , Bouziotis Penelope , Georgoulias Panagiotis , Valotassiou Varvara , Tsotakos Theodoros , Loudos George
Published: April 2013

Nanomedicine applications have recently gathered great attention in terms of their revolutionary properties and multivalency. Nanoparticles (NPs) have proven useful owing to their size, surface and kinetics advantages, as well as their ability to be functionalized with targeting, imaging and therapeutic moieties. Nuclear medicine is actively involved in nano‐research innovative breakthrough efforts in multiple applications, through the radiolabeling of NP structures. There are several ways that NP‐radiolabeling can be approached depending on the radionuclide that is used and the NP type. The radiolabeling of NPs with the most widely and easily available radiometal, which is 99mTc, is the focus of this review. Copyright © 2013 John Wiley & Sons, Ltd.
A New Approach for the Simulation of Electrochemiluminescence (ECL)
Authors: Klymenko Oleksiy V. , Svir Irina , Amatore Christian
Published: April 2013

The validity and accuracy of our new numerical approach implemented in KISSA‐1D software when applied to a theoretical study of different types of electrochemiluminescence (ECL) is established by comparison with existing analytical solutions and others specifically derived in this work, as well as with independent numerical solutions obtained by using commercial software. The efficiency and comprehensiveness of this approach are illustrated by using a representative series of published ECL reaction schemes taken as typical case studies when ECL is generated by a single electrode under amperometric or voltammetric conditions, even when rate constants used in the simulations far exceed any of their realistic experimental limits.
Elucidating Inorganic Nanoscale Species in Solution: Complementary and Corroborative Approaches
Authors: Oliveri Anna F. , Elliott Edward W. , Carnes Matthew E. , Hutchison James E. , Johnson Darren W.
Published: April 2013

The challenge of defining a length on the nanoscale is non‐trivial. For a well‐defined inorganic nanoscale species, a size measurement can describe a number of different dimensions (core, shell, solvation sphere). Often size is reported out of context or even inadvertently misrepresented. Since many of the techniques used to measure size depend on significant and sometimes destructive sample preparation, an additional challenge is defining “what size means” for a nanoscale species in solution. In this Concept, the distinction is made between complementary techniques that can be used together to unveil more information about the material in question, and corroborative techniques, which are used to make multiple measurements of the same property. Additionally, corroborative techniques can be used to measure the same property in and out‐of solution so as to reveal details about solution behaviour. We highlight various approaches to this characterization challenge in the context of three case studies that demonstrate the use of both complementary and corroborative techniques to elucidate the various functional dimensions of different types of inorganic nanoscale species in solution.
Controlled Synthesis of Manganese Oxyhydroxide Nanotubes: Implications for High‐Efficiency Supercapacitors
Authors: Tan Hui Teng , Rui Xianhong , Shi Wenhui , Xu Chen , Yu Hong , Hoster Harry E. , Yan Qingyu
Published: April 2013

Successful attempts have been made to control the synthesis of tubular MnOOH with nanodimensions on high electronic conductivity graphite felt (GF) to be used as a flexible supercapacitor electrode. As a fundamental study, the time‐dependent kinetics was investigated to interpret its formation mechanism, which can be depicted as the curling of a two‐dimensional precursor into a one‐dimensional structure with a hollow interior. As a result of the nanotube structure, the active surface area of MnOOH is completely accessible to electrolyte ions and has a shorter charge‐transport length and greater ability to withstand structural deformation. Hence, hollow‐structured MnOOH shows great promise as an electrochemical system, which is reflected in its high specific capacitance of 1156 F g−1 at 1 A g−1. Furthermore, the high energy density of 1125 W h kg−1 and power density of 5.05 kW kg−1 reveal the outstanding energy‐storage behavior of the MnOOH/GF composites as flexible supercapacitor electrodes.
A rare case of serial killing by poisoning
Authors: Vuori Erkki , Pelander Anna , Rasanen Ilpo , Juote Mikko , Ojanperä Ilkka
Published: April 2013

A case of serial killing by poisoning by a 59‐year‐old practical nurse is discussed. Following a report by an emergency‐room doctor of an attempted murder, police performed an investigation into all deaths of patients in the nurse's care. Earlier, a medico‐legal cause‐of‐death investigation had been performed on two of these cadavers, but in the other three cases the death certificate had been issued after a medical investigation only. In two of these latter cases, the body had been cremated, but fixed histological samples taken at medical autopsy were available, while in one case the person had died recently and the body was thereafter exhumed and autopsied. All of the suspected victims were older people who required nursing, and the nurse's course of action was consistent in all cases. In the absence of ordinary post‐mortem toxicology samples in the medical cases, extraordinary evidence – paraffin‐embedded liver tissue samples originally taken for histology at autopsy – was successfully recovered in two cases and analyzed for drugs. In all five cases, drugs not prescribed to the patient were detected, including digoxin, dixyrazine, citalopram, venlafaxine, and benzodiazepines (diazepam, chlordiazepoxide, temazepam, and oxazepam). The nurse was eventually found guilty of five murders by poisoning, five attempted murders, and three aggravated assaults. The nurse was sentenced to life imprisonment. Copyright © 2013 John Wiley & Sons, Ltd.
A novel approach with “skeletonised MTR” measures tract‐specific microstructural changes in early primary‐progressive MS
Authors: Bodini Benedetta , Cercignani Mara , Toosy Ahmed , Stefano Nicola De , Miller David H. , Thompson Alan J. , Ciccarelli Olga
Published: April 2013

We combined tract‐based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract‐specific short‐term changes in early primary‐progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty‐one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM “skeleton,” which represents the tracts that are “common” to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co‐registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a “skeletonised” MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow‐up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal‐appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract‐specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross‐subject and tract‐specific changes in MTR. Hum Brain Mapp 35:723–733, 2014. © 2013 Wiley Periodicals, Inc.
Unsupervised classification of major depression using functional connectivity MRI
Authors: Zeng Ling‐Li , Shen Hui , Liu Li , Hu Dewen
Published: April 2013

The current diagnosis of psychiatric disorders including major depressive disorder based largely on self‐reported symptoms and clinical signs may be prone to patients' behaviors and psychiatrists' bias. This study aims at developing an unsupervised machine learning approach for the accurate identification of major depression based on single resting‐state functional magnetic resonance imaging scans in the absence of clinical information. Twenty‐four medication‐naive patients with major depression and 29 demographically similar healthy individuals underwent resting‐state functional magnetic resonance imaging. We first clustered the voxels within the perigenual cingulate cortex into two subregions, a subgenual region and a pregenual region, according to their distinct resting‐state functional connectivity patterns and showed that a maximum margin clustering‐based unsupervised machine learning approach extracted sufficient information from the subgenual cingulate functional connectivity map to differentiate depressed patients from healthy controls with a group‐level clustering consistency of 92.5% and an individual‐level classification consistency of 92.5%. It was also revealed that the subgenual cingulate functional connectivity network with the highest discriminative power primarily included the ventrolateral and ventromedial prefrontal cortex, superior temporal gyri and limbic areas, indicating that these connections may play critical roles in the pathophysiology of major depression. The current study suggests that subgenual cingulate functional connectivity network signatures may provide promising objective biomarkers for the diagnosis of major depression and that maximum margin clustering‐based unsupervised machine learning approaches may have the potential to inform clinical practice and aid in research on psychiatric disorders. Hum Brain Mapp 35:1630–1641, 2014. © 2013 Wiley Periodicals, Inc.
A framework for the design of flexible cross‐talk functions for spatial filtering of EEG/MEG data: DeFleCT
Authors: Hauk Olaf , Stenroos Matti
Published: April 2013

Brain activation estimated from EEG and MEG data is the basis for a number of time‐series analyses. In these applications, it is essential to minimize “leakage” or “cross‐talk” of the estimates among brain areas. Here, we present a novel framework that allows the design of flexible cross‐talk functions (DeFleCT), combining three types of constraints: (1) full separation of multiple discrete brain sources, (2) minimization of contributions from other (distributed) brain sources, and (3) minimization of the contribution from measurement noise. Our framework allows the design of novel estimators by combining knowledge about discrete sources with constraints on distributed source activity and knowledge about noise covariance. These estimators will be useful in situations where assumptions about sources of interest need to be combined with uncertain information about additional sources that may contaminate the signal (e.g. distributed sources), and for which existing methods may not yield optimal solutions. We also show how existing estimators, such as maximum‐likelihood dipole estimation, L2 minimum‐norm estimation, and linearly‐constrained minimum variance as well as null‐beamformers, can be derived as special cases from this general formalism. The performance of the resulting estimators is demonstrated for the estimation of discrete sources and regions‐of‐interest in simulations of combined EEG/MEG data. Our framework will be useful for EEG/MEG studies applying time‐series analysis in source space as well as for the evaluation and comparison of linear estimators. Hum Brain Mapp 35:1642–1653, 2014. © 2013 Wiley Periodicals, Inc.
The recognition of biomaterials: Pattern recognition of medical polymers and their adsorbed biomolecules
Authors: Love Ryan J. , Jones Kim S.
Published: April 2013

All biomedical materials are recognized as foreign entities by the host immune system despite the substantial range of different materials that have been developed by material scientists and engineers. Hydrophobic biomaterials, hydrogels, biomaterials with low protein binding surfaces, and those that readily adsorb a protein layer all seem to incite similar host responses in vivo that may differ in magnitude, but ultimately result in encapsulation by fibrotic tissue. The recognition of medical materials by the host is explained by the very intricate pattern recognition system made up of integrins, toll‐like receptors, scavenger receptors, and other surface proteins that enable leukocytes to perceive almost any foreign body. In this review, we describe the various pattern recognition receptors and processes that occur on biomedical material surfaces that permit detection of a range of materials within the host. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2740–2752, 2013.
Fabrication and in vivo thrombogenicity testing of nitric oxide generating artificial lungs
Authors: Amoako Kagya A. , Montoya Patrick J. , Major Terry C. , Suhaib Ahmed B. , Handa Hitesh , Brant David O. , Meyerhoff Mark E. , Bartlett Robert H. , Cook Keith E.
Published: April 2013

Hollow fiber artificial lungs are increasingly being used for long‐term applications. However, clot formation limits their use to 1–2 weeks. This study investigated the effect of nitric oxide generating (NOgen) hollow fibers on artificial lung thrombogenicity. Silicone hollow fibers were fabricated to incorporate 50 nm copper particles as a catalyst for NO generation from the blood. Fibers with and without (control) these particles were incorporated into artificial lungs with a 0.1 m2 surface area and inserted in circuits coated tip‐to‐tip with the NOgen material. Circuits (N = 5/each) were attached to rabbits in a pumpless, arterio‐venous configuration and run for 4 h at an activated clotting time of 350–400 s. Three control circuits clotted completely, while none of the NOgen circuits failed. Accordingly, blood flows were significantly higher in the NOgen group (95.9 ± 11.7, p < 0.01) compared to the controls (35.2 ± 19.7; mL/min), and resistance was significantly higher in the control group after 4 h (15.38 ± 9.65, p < 0.001) than in NOgen (0.09 ± 0.03; mmHg/mL/min). On the other hand, platelet counts and plasma fibrinogen concentration expressed as percent of baseline in control group (63.7 ± 5.7%, 77.2 ± 5.6%; p < 0.05) were greater than those in the NOgen group (60.4 ± 5.1%, 63.2 ± 3.7%). Plasma copper levels in the NOgen group were 2.8 times baseline at 4 h (132.8 ± 4.5 μg/dL) and unchanged in the controls. This study demonstrates that NO generating gas exchange fibers could be a potentially effective way to control coagulation inside artificial lungs. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3511–3519, 2013.
Bioactive effects of graphene oxide cell culture substratum on structure and function of human adipose‐derived stem cells
Authors: Kim Jangho , Choi Kyoung Soon , Kim Yeonju , Lim Ki‐Tack , Seonwoo Hoon , Park Yensil , Kim Deok‐Ho , Choung Pill‐Hoon , Cho Chong‐Su , Kim Soo Young , Choung Yun‐Hoon , Chung Jong Hoon
Published: April 2013

Nanoscale topography of artificial substrates can greatly influence the fate of stem cells including adhesion, proliferation, and differentiation. Thus the design and manipulation of nanoscale stem cell culture platforms or scaffolds are of great importance as a strategy in stem cell and tissue engineering applications. In this report, we propose that a graphene oxide (GO) film is an efficient platform for modulating structure and function of human adipose‐derived stem cells (hASCs). Using a self‐assembly method, we successfully coated GO on glass for fabricating GO films. The hASCs grown on the GO films showed increased adhesion, indicated by a large number of focal adhesions, and higher correlation between the orientations of actin filaments and vinculin bands compared to hASCs grown on the glass (uncoated GO substrate). It was also found that the GO films showed the stronger affinity for hASCs than the glass. In addition, the GO film proved to be a suitable environment for the time‐dependent viability of hASCs. The enhanced differentiation of hASCs included osteogenesis, adipogenesis, and epithelial genesis, while chondrogenic differentiation of hASCs was decreased, compared to tissue culture polystyrene as a control substrate. The data obtained here collectively demonstrates that the GO film is an efficient substratum for the adhesion, proliferation, and differentiation of hASCs. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3520–3530, 2013.
Preparation of well‐defined calcium cross‐linked alginate films for the prevention of surgical adhesions
Authors: Esser Eva , Tessmar Joerg K. V.
Published: April 2013

Abdominal adhesions are one of the major problems associated with abdominal surgeries or abdominal trauma. There are many different therapeutic options to prevent these adhesions, for example, the application of barrier films made of biodegradable polymers like alginate. For many application relevant parameters (mechanical stability, elasticity, erosion, and mucoadhesivity of the films), the extent of cross‐linking with divalent cations, such as calcium, is essential to obtain alginate films with clinically ideal properties. All these properties can eventually be strongly influenced by the composition of the films. For this reason, the manufacture of thin films (≈20 µm) was improved to accurately control the calcium content and distribution as well as the time and process of cross‐linking. The aim of this work was to find the best suited method to evenly distribute the calcium ions in the alginate films and to obtain films with controlled erosion times as well as sufficient flexibility and stability. Furthermore, the influence of plasticizers on the mechanical stability and elasticity was tested to find the amount and type of plasticizers that have to be added to produce the best suited films. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men
Authors: Bliuc Dana , Nguyen Nguyen D , Nguyen Tuan V , Eisman John A , Center Jacqueline R
Published: April 2013

After fracture there is increased risk of refracture and premature mortality. These outcomes, particularly premature mortality following refracture, have not previously been studied together to understand overall mortality risk. This study examined the long-term cumulative incidence of subsequent fracture and total mortality with mortality calculated as a compound risk and separated according to initial and refracture. Community-dwelling participants aged 60+ years from Dubbo Osteoporosis Epidemiology Study with incident fractures, followed prospectively for further fractures and deaths from 1989 to 2010. Subsequent fracture and mortality ascertained using cumulative incidence competing risk models allowing four possible outcomes: death without refracture; death following refracture; refracture but alive, and event-free. There were 952 women and 343 men with incident fracture. Within 5 years following initial fracture, 24% women and 20% men refractured; and 26% women and 37% men died without refracture. Of those who refractured, a further 50% of women and 75% of men died, so that total 5-year mortality was 39% in women and 51% in men. Excess mortality was 24% in women and 27% in men. Although mortality following refracture occurred predominantly in the first 5 years post–initial fracture, total mortality (post-initial and refracture) was elevated for 10 years. Most of the 5-year to 10-year excess mortality was associated with refracture. The long-term (>10 years) refracture rate was reduced, particularly in the elderly as a result of their high mortality rate. The 30% alive beyond 10 years postfracture were at low risk of further adverse outcomes. Refractures contribute substantially to overall mortality associated with fracture. The majority of the mortality and refractures occurred in the first 5 years following the initial fracture. However, excess mortality was observed for up to 10 years postfracture, predominantly related to that after refracture. © 2013 American Society for Bone and Mineral Research.
The potential of carbon‐11 and fluorine‐18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa
Authors: Damont Annelaure , Roeda Dirk , Dollé Frédéric
Published: April 2013

The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is upregulated in the brain of subjects suffering from neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to microglia activation making thus the TSPO a marker of choice of neuroinflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short‐lived positron‐emitter isotopes carbon‐11 and fluorine‐18 emerged in the mid‐1980s with the preparation of the 3‐isoquinolinecarboxamide [11C]PK11195. To date, an impressive number of promising compounds—[11C]PK11195‐challengers—have been developed; some radioligands—for example, [11C]PBR28, [11C]DPA‐713, [18F]FEDAA1106 and [18F]DPA‐714—are currently used in clinical trials. As illustrated in this review, the methodologies applied for the preparation of these compounds remain mainly [11C]methylations using [11C]MeI or [11C]MeOTf and SN2‐type nucleophilic aliphatic [18F]fluorinations—two processes illustrating the state‐of‐the‐art arsenal of reactions that involves these two short‐lived radioisotopes—but alternative processes, such as [11C]carbonylations using [11C]CO and [11C]COCl2 as well as SNAr‐type nucleophilic [18F]fluorinations, have also been reported and as such, reviewed herein.
Radioligands targeting P‐glycoprotein and other drug efflux proteins at the blood–brain barrier
Authors: Wanek Thomas , Mairinger Severin , Langer Oliver
Published: April 2013

Brain penetration of radiopharmaceuticals or therapeutic drugs may be restricted by adenosine triphosphate‐binding cassette (ABC) transporters, such as P‐glycoprotein (Pgp), breast cancer resistance protein (BCRP), or the multidrug resistance‐associated proteins. These transporters are expressed in the luminal membrane of brain capillary endothelial cells forming the blood–brain barrier (BBB), where they actively efflux a wide range of chemically unrelated compounds from the brain back into the blood. Most efforts to visualize ABC transporters at the BBB with positron emission tomography have concentrated on Pgp. Pgp imaging probes can be classified as radiolabeled substrates or inhibitors. The radiolabeled substrates (R)‐[11C]verapamil and [11C]‐N‐desmethyl‐loperamide have been successfully used to assess Pgp function at the BBB of animals and humans. Radiolabeled Pgp inhibitors, such as [11C]tariquidar, [11C]elacridar, or [11C]laniquidar, were developed to measure Pgp expression levels at the BBB, which has so far remained unsuccessful as these probes were unexpectedly recognized at tracer concentrations by Pgp and BCRP as substrates resulting in low brain uptake. Studies on positron emission tomography tracers for other ABC transporters than Pgp (BCRP and multidrug resistance‐associated proteins) are still in their infancy. It is hoped that the experience gained with the imaging of Pgp will be successfully translated to the development of radiotracers to visualize other ABC transporters.Copyright © 2013 John Wiley & Sons, Ltd.
PET radioligands for the vesicular transporters for monoamines and acetylcholine
Authors: Kilbourn Michael R.
Published: April 2013

The vesicular transporters for the monoamine and acetylcholine have been successfully targeted for the development of radioligands for human brain imaging. The vesicular monoamine transporter type 2 ligands are based on the structure of tetrabenazine, a known clinically used drug. In contrast, the radioligands for vesicular acetylcholine transporter are based on vesamicol, a toxic xenobiotic. The similarities and differences in the development of these two classes of radioligands are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Current status of positron emission tomography radiotracers for serotonin receptors in humans
Authors: Zimmer Luc , Le Bars Didier
Published: April 2013

Serotonin (5‐HT) neurotransmission plays a key modulatory role in the brain. This system is critical for pathophysiological processes and many drug treatments for brain disorders interact with its 14 subtypes of receptors. Positron emission tomography (PET) is a unique tool for the study of the living brain in translational studies from animal models to patients in neurology or psychiatry. This short review is intended to cover the current status of PET radioligands used for imaging human brain 5‐HT receptors. Here, we describe the available PET radioligands for the 5‐HT1A, 5‐HT1B, 5‐HT2A, 5‐HT4 and 5‐HT6 receptors. Finally, we highlight the future challenges for a functional PET imaging of serotonin receptors, including the research towards specific PET radiotracers for yet unexplored serotonin receptors, the need of radiotracers for endogenous serotonin level measurement and the contribution of agonist radiotracers for functional imaging of 5‐HT neurotransmission.
Nucleoside‐based probes for imaging tumor proliferation using positron emission tomography
Authors: Alauddin Mian M.
Published: April 2013

Cancer is one of the leading causes of human death, and early detection can be beneficial for its timely therapy and management. For the early detection of cancer, positron emission tomography (PET) is more accurate and sensitive than other imaging modalities, such as computed tomography and magnetic resonance imaging. [18F]‐Labeled fluorodeoxyglucose is the most useful PET probe in early detection of cancer; however, its nonspecific accumulation and consequent false–positive findings warrant the identification of other PET probes. Thymidine (TdR) and its analogs have been radiolabeled for PET imaging of cellular proliferation and DNA synthesis. Because of its in vivo instability, radiolabeled TdR has not been successful in PET imaging. However, some of its radiolabeled analogs have been developed for PET imaging of cellular proliferation and DNA synthesis. In this review, the radiochemistry and production of 11C‐TdR and 11C/18F‐labeled TdR analogs published to date are presented. Copyright © 2013 John Wiley & Sons, Ltd.
Positron emission tomography radioligands for the opioid system
Authors: Dannals Robert F.
Published: April 2013

Opiate receptors are found in the brain, the spinal cord, some peripheral sensory neurons, and the gastrointestinal tract. Naturally occurring and synthetic opiate ligands exert their influence on a wide variety of processes including analgesia, euphoria, dysphoria, sedation, respiratory depression, and miosis and are frequently topics for discussions on addiction and physical dependence. This review looks at the history of positron emission tomography radioligands for probing this receptor system.
Tropane‐derived 11C‐labelled and 18F‐labelled DAT ligands
Authors: Riss P. J. , Stockhofe K. , Roesch F.
Published: April 2013

Radiolabelling of cocaine‐derived 3‐phenyltropanes for dopamine transporter positron emission tomography with 18F and 11C is reviewed. Copyright © 2013 John Wiley & Sons, Ltd.
Recent PET radioligands with optimal brain kinetics for imaging nicotinic acetylcholine receptors
Authors: Horti Andrew G. , Kuwabara Hiroto , Holt Daniel P. , Dannals Robert F. , Wong Dean F.
Published: April 2013

Cerebral neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in various neurophysiological processes and in the pathophysiology and/or treatment strategies of various disorders.

Positron emission tomography (PET) imaging of nAChR and, especially, the most prominent cerebral subtype α4β2‐nAChR is important in smoking, epilepsy, attention deficit hyperactivity disorder, depression, schizophrenia, cognition, behavior, memory, and in research involving aging, cognitive impairments, and dementia. Most human α4β2‐nAChR PET imaging has been performed with 2‐[18F]FA, but slow brain kinetics is the substantial drawback of 2‐[18F]FA that precludes widespread PET imaging research of nAChR in humans. Development of a better PET radioligand for α4β2‐nAChR was a focus of substantial investigation that has been thoroughly reviewed (up to 2009) previously.

This article attempts to summarize the peer‐reviewed publications of the most recent development and preclinical studies of novel α4β2‐nAChR PET radioligands with improved brain kinetics and first human studies with one of these radioligands ([18F]AZAN).
Endogenous compounds labeled with radionuclides of short half‐life—some perspectives
Authors: Långström B. , Karimi F. , Watanabe Y.
Published: April 2013

In the article, the strategy and synthesis of some endogenous compounds labeled mainly with 11C are presented. There are some examples illustrating how endogenous labeled compounds in connection with positron emission tomography have unique properties to describe various biological processes, and a few examples of the use of tracers labeled with 13N and 15O are also discussed.

Labeled endogenous compounds may be an important asset to describe the conditions and the status of biological systems and might therefore be a key for the future search of individualized medicine. Copyright © 2013 John Wiley & Sons, Ltd.
11C‐labeled and 18F‐labeled PET ligands for subtype‐specific imaging of histamine receptors in the brain
Authors: Funke Uta , Vugts Danielle J. , Janssen Bieneke , Spaans Arnold , Kruijer Perry S. , Lammertsma Adriaan A. , Perk Lars R. , Windhorst Albert D.
Published: April 2013

The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus.

In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype‐selective carbon‐11‐labeled and fluorine‐18‐labeled compounds for imaging in the brain.

Using specific radioligands, the H1R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1R occupancy. The H3R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3R PET imaging studies in humans have been reported. The H4R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4R‐specific 11C‐labeled ligands have been synthesized, and the imaging of the H4R in vivo is in the early stage.
Ototoxicity of olive oil in a chinchilla animal model
Authors: Emami Nader , Daniel Sam J.
Published: April 2013

Objectives/Hypothesis

Olive oil is often used by patients to soften ear wax or to relieve ear canal obstruction. It is also sold in drugstores as a cerumenolytic. To date, no study has assessed the safety of ototopical olive oil on hearing in the presence of tympanic membrane perforation. The present study aimed to assess the safety of ototopic olive oil on hearing in the presence of tympanic membrane perforation.

Study Design

Prospective, randomized, controlled trial in a chinchilla animal model.

Materials and methods

Eleven chinchillas underwent bilateral myringotomy. In each animal, one ear was randomly assigned to receive olive oil (experimental ear), while the contralateral control ear received normal saline. Auditory brain response (ABR) test was performed at baseline and then 7, 14, and 30 days following the application.

Results

At 30 days follow‐up, there was no significant change in auditory brain response thresholds at 8, 16, 20, or 25 kHz. Scanning electron microscope imaging showed no damage to the hair cells.

Conclusion

Olive oil does not seem to cause hearing loss in chinchillas with perforated tympanic membranes. Future clinical studies are required.

Level of Evidence

N/A Laryngoscope, 123:2009–2012, 2013