bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Hallmarks of a Catalytic DNA that Makes Lariat RNA
Authors: Javadi‐Zarnaghi Fatemeh , Höbartner Claudia
Published: November 2015

Catalytic DNAs, also known as deoxyribozymes, are of practical value for the synthesis of structurally or topologically complex RNAs, but little is known about the molecular details of DNA catalysis. We have investigated a deoxyribozyme that catalyzes the formation of a specific intramolecular 2′,5′‐phosphodiester bond to produce lariat RNA, which is an important biological intermediate in eukaryotic mRNA splicing. The results of combinatorial mutation interference analysis (CoMA) allowed us to shrink the catalytic core to 70 % of its original length and revealed that the essential part of the deoxyribozyme sequence contained more than 50 % guanosines. Nucleotide analogue interference mapping (dNAIM) and dimethyl sulfate interference (DMSi) experiments provided atomic details of individual guanosine functional groups. Additional spectroscopic experiments and structural probing data identified conformational changes upon metal‐ion binding and catalysis. Overall, this comprehensive analysis of the DNA‐catalyzed reaction has provided specific insights into the synthesis of 2′,5′‐branched RNA, and suggested the general features of deoxyribozymes that catalyze nucleic acid ligation reactions.
Polyaromatic Profluorescent Nitroxide Probes with Enhanced Photostability
Authors: Lussini Vanessa C. , Blinco James P. , Fairfull‐Smith Kathryn E. , Bottle Steven E.
Published: November 2015

Novel profluorescent mono‐ and bis‐isoindoline nitroxides linked to napthalimide and perylene diimide structural cores are described. These nitroxide‐fluorophore probes display strongly suppressed fluorescence in comparison to their corresponding non‐radical diamagnetic methoxyamine derivatives. The perylene‐based probe possessing two isoindoline systems tethered through ethynyl linkages was shown to be the most photostable in solution, demonstrating significantly enhanced longevity over the 9,10‐bis(phenylethynyl)anthracene fluorophore used in previous profluorescent nitroxide probes.
Influence of pH on the Motion of Catalytic Janus Particles and Tubular Bubble‐Propelled Micromotors
Authors: Moo James Guo Sheng , Wang Hong , Pumera Martin
Published: November 2015

Self‐propelled miniaturized machines harness the chemical potential of their environment for movement. Locomotion of chemically powered micromotors have been hugely dependent on the surroundings. The use of pH to alter the mobility of micromotors is demonstrated in this work through the manipulation of hydrogen peroxide chemistry in different acidity/alkalinity. The sequential addition of sodium hydroxide to increase the pH of the solution led to a consequent increase in activity of micromotors. Meanwhile, addition of hydrochloric acid compromised the structural integrity of the microstructures, culminating in locomotive changes. Such dramatic changes in activity and velocities of the micromotors allow the usage of this behavior for pH detection. This concept was illustrated with Janus silver micromotors and tubular bimetallic Cu/Pt micromotors. Alteration of pH serves as a useful general strategy for increasing hydrogen peroxide decomposition for enhanced oxygen‐bubble propulsion in catalytic micromotors.
Towards Clarifying the Role of O2 during the Phthalocyanine Synthesis
Authors: Wang Kang , Pan Houhe , Jiang Jianzhuang
Published: November 2015

The role of O2 within the synthesis of phthalocyanines (Pcs) has remained unclear in the past century. Here, we demonstrate that O2, in cooperation with the solvent n‐pentanol, participates in the cyclic tetramerization of phthalonitriles over the half‐sandwich complex template [Lu(Pc)(acac)] (acac=acetylacetonate) and terminates the reaction at the stage of uncyclized isoindole oligomeric derivatives rather than the phthalocyanine chromophores, resulting in the isolation of the heteroleptic (phthalocyaninato)(triisoindole‐1‐one) lutetium double‐decker complexes [(Pc)Lu(TIO‐I)] (TIO‐I=3,4,7,8,11,12‐sexi(2,6‐diisopropylphenoxy)‐15‐[4,5‐di(2,6‐diisopropylphenoxy)‐2‐cyanobenzimidamido]triisoindole‐1‐one) and [(Pc)Lu(TIO‐II)] (TIO‐II=3,4,7,8,11,12‐sexi(2,6‐dimethylphenoxy)‐15‐[4,5‐di(2,6‐dimethylphenoxy)‐2‐cyanobenzimidamido]triisoindole‐1‐one) with the help of bulky substituents at the phthalonitrile periphery and an unsubstituted phthalocyanine ligand in the double‐decker skeleton. Nevertheless, the cyclic tetramerization of the phthalonitriles was revealed to be sensitive to O2 with the reaction progression also depending on the oxygen concentration/content, leading to the O2‐senstive and ‐dependent nature for the isolation of phthalocyanine derivatives.
Strategy Approach for Direct Enantioseparation of Hyoscyamine Sulfate and Zopiclone on a Chiral αl‐Acid Glycoprotein Column and Determination of Their Eutomers: Thermodynamic Study of Complexation
Authors: Zaazaa Hala E. , Salama Nahla N. , Abd El Halim Lobna M. , Salem Maissa Y. , Abd El Fattah Laila E.
Published: November 2015

Rapid and simple isocratic high‐performance liquid chromatographic methods with UV detection were developed and validated for the direct resolution of racemic mixtures of hyoscyamine sulfate and zopiclone. The method involved the use of αl‐acid glycoprotein (AGP) as chiral stationary phase. The stereochemical separation factor (ά) and the stereochemical resolution factor (Rs) obtained were 1.29 and 1.60 for hyoscyamine sulfate and 1.47 and 2.45 for zopiclone, respectively. The method was used for determination of chiral switching (eutomer) isomers: S‐hyoscyamine sulfate and eszopiclone. Several mobile phase parameters were investigated for controlling enantioselective retention and resolution on the chiral AGP column. The influence of mobile phase, concentration and type of uncharged organic modifier, ionic strength, and column temperature on enantioselectivity were studied. Calibration curves were linear in the ranges of 1–10 µg mL‐1 and 0.5–5 µg mL‐1 for S‐hyoscyamine sulfate and eszopiclone, respectively. The method is specific and sensitive, with lower limits of detection and quantifications of 0.156, 0.515 and 0.106, 0.349 for S‐hyoscyamine sulfate and eszopiclone, respectively. The method was used to identify quantitatively the enantiomers profile of the racemic mixtures of the studied drugs in their pharmaceutical preparations. Thermodynamic studies were performed to calculate the enthalpic ΔH and entropic ΔS terms. The results showed that enantiomer separation of the studied drugs were an enthalpic process. Chirality 28:49–57, 2016. © 2015 Wiley Periodicals, Inc.
Enantiopure Indolizinoindolones with in vitro Activity against Blood‐ and Liver‐Stage Malaria Parasites
Authors: Pereira Nuno A. L. , Monteiro Ângelo , Machado Marta , Gut Jiri , Molins Elies , Perry M. Jesus , Dourado Jorge , Moreira Rui , Rosenthal Philip J. , Prudêncio Miguel , Santos Maria M. M.
Published: November 2015

Malaria continues to be a major cause of morbidity and mortality to this day, and resistance to drugs like chloroquine has led to an urgent need to discover novel chemical entities aimed at new targets. Here, we report the discovery of a novel class of potential antimalarial compounds containing an indolizinoindolone scaffold. These novel enantiopure indolizinoindolones were synthesized, in good‐to‐excellent yields and excellent diastereoselectivities, by cyclocondensation reaction of (S)‐ or (R)‐tryptophanol and 2‐acyl benzoic acids, followed by intramolecular α‐amidoalkylation. Interestingly, we were able to synthesize for the first time 7,13b‐cis indolizinoindolones in a two‐step route. The novel compounds showed promising activity against erythrocytic stages of the human malaria parasite, Plasmodium falciparum, and liver stages of the rodent parasite Plasmodium berghei. In particular, an (S)‐tryptophanol‐derived isoindolinone was identified as a promising starting scaffold to search for novel antimalarials, combining excellent activity against both stages of the parasite′s life cycle with low cytotoxicity and excellent metabolic and chemical stability in vitro.
Design of PID controllers using Filippov's method for stable operation of DC–DC converters
Authors: Hayes Brendan , Condon Marissa , Giaouris Damian
Published: November 2015

A lot of work has taken place into the design and control of DC–DC converters, and various methodologies have been proposed. While traditionally only P or PI controllers have been employed, recent applications that require a fast transient performance impose the usage of the derivative, D, term. As it is well known, using the D‐term can cause numerous problems in such converters that greatly downgrade their performance and lifetime. Having said that, in this paper, we first prove that by using the D‐term, it is possible to increase the stability margin (and hence keep a low current ripple), and then, we present a novel method to tune the PID controller that guarantees a fast and stable response over a wide range of parameter values without using an unreasonably high value of the derivative gain that magnifies the presence of noise in the system. The controller is designed utilising Filippov's method, and a simple and easy to implement strategy is proposed. Furthermore, an adaptive PID controller is designed whose gains are changed depending on the value of the supply voltage or output load. Another important contribution of this work is the derivation of the saltation matrix when the switching manifold is discontinuous, the complete proof is presented, and the results validated. Copyright © 2015 John Wiley & Sons, Ltd.
Expression of CD2 and CD25 on mast cell populations can be seen outside the setting of systemic mastocytosis
Authors: Cherian Sindhu , McCullouch Vivian , Miller Valerie , Dougherty Katy , Fromm Jonathan R. , Wood Brent L.
Published: November 2015

Background

Systemic mastocytosis (SM) is a diagnosis made using clinical, laboratory, and histologic parameters. Aberrant CD2 and/or CD25 expression on mast cells provides one minor criterion for a diagnosis of SM. To validate a tube (CD45/CD117/CD2/CD25) for mast cell evaluation, flow cytometry (FC) on residual material from marrow aspirates samples submitted to the hematopathology laboratory was performed.

Methods

Samples evaluated (n = 98) had no clinical or morphologic suspicion for SM. Samples were excluded if there was history of a myeloid stem cell neoplasm. Ten documented cases of SM were evaluated for comparison.

Results

Among cases without history of SM, 17.3% (n = 17) showed expression of CD2 and/or CD25 on ≥10% of the mast cell population (CD25 alone in 14 cases, CD2 alone in 2 cases, both in one case), while 82.6% (n = 81) showed no expression of these antigens. The percentage of mast cells showing aberrant CD2 and/or CD25 expression respectively ranged from 12.1% to 98.8% and 22.2% to 95.7% Interestingly, all of the cases with evidence of aberrant antigen expression on mast cells were collected post‐therapy while 22.1% of the negative samples were collected pre‐therapy. A cut‐off of 60% CD25 expression on mast cells identified all cases of SM while minimizing false positives.

Conclusions

These findings demonstrate that aberrant expression of CD2 and/or CD25 may be seen on mast cells outside of the setting of SM. The data suggests that this phenomenon may be seen more commonly following chemotherapy and that FC of mast cells should be interpreted with caution in the post‐chemotherapy setting. © 2015 International Clinical Cytometry Society
Temporal and spatial requirements for Nodal‐induced anterior mesendoderm and mesoderm in anterior neurulation
Authors: Gonsar Ngawang , Coughlin Alicia , Clay‐Wright Jessica A. , Borg Bethanie R. , Kindt Lexy M. , Liang Jennifer O.
Published: November 2015

Zebrafish with defective Nodal signaling have a phenotype analogous to the fatal human birth defect anencephaly, which is caused by an open anterior neural tube. Previous work in our laboratory found that anterior open neural tube phenotypes in Nodal signaling mutants were caused by lack of mesendodermal/mesodermal tissues. Defects in these mutants are already apparent at neural plate stage, before the neuroepithelium starts to fold into a tube. Consistent with this, we found that the requirement for Nodal signaling maps to mid‐late blastula stages. This timing correlates with the timing of prechordal plate mesendoderm and anterior mesoderm induction, suggesting these tissues act to promote neurulation. To further identify tissues important for neurulation, we took advantage of the variable phenotypes in Nodal signaling‐deficient sqt mutant and Lefty1‐overexpressing embryos. Statistical analysis indicated a strong, positive correlation between a closed neural tube and presence of several mesendoderm/mesoderm‐derived tissues (hatching glands, cephalic paraxial mesoderm, notochord, and head muscles). However, the neural tube was closed in a subset of embryos that lacked any one of these tissues. This suggests that several types of Nodal‐induced mesendodermal/mesodermal precursors are competent to promote neurulation. genesis 54:3–18, 2016. © 2016 Wiley Periodicals, Inc.
Synthesis and Evaluation of the Antiproliferative Properties of a Tethered Tubercidin–Platinum(II) Complex
Authors: D'Errico Stefano , Oliviero Giorgia , Borbone Nicola , Di Gennaro Elena , Zotti Andrea Ilaria , Budillon Alfredo , Cerullo Vincenzo , Nici Fabrizia , Mayol Luciano , Piccialli Vincenzo , Piccialli Gennaro
Published: November 2015

Herein, the synthesis of a nucleoside platinum(II) complex in which a cisplatin‐like unit is joined to 7‐deazaadenosine through an amino alkyl chain installed at the C6 position of purine was explored. The capability of the new complex to react with DNA purine bases was confirmed by a model reaction with deoxyguanosine monophosphate, whereas its antiproliferative activity against A549 and Cal27 human cancer cell lines was studied by sulforhodamine B assay in comparison with its unplatinated precursor and cisplatin.
Development of Nonenzymatic Hydrogen Peroxide Sensor Based on Successive Pd‐Ag Electrodeposited Nanoparticles on Glassy Carbon Electrode
Authors: Roushani Mahmoud , Dizajdizi Behruz Zare
Published: November 2015

A novel strategy to fabricate hydrogen peroxide (H2O2) sensor was developed by electrodepositing palladiumsilver nanoparticles (NPs) on a glassy carbon electrode. The morphology of the modified electrode was characterized by Scanning electron microscopy (SEM). The result of electrochemical experiments showed that such constructed sensor had a favorable catalytic ability, high sensitivity, excellent selectivity towards reduction of hydrogen peroxide (H2O2). The response to H2O2 is linear in the range between 0.30 μM to 2.50 mM, and the detection limit is 0.1 μM (at an S/N of 3).
Markovian modeling of seismic damage accumulation
Authors: Iervolino Iunio , Giorgio Massimiliano , Chioccarelli Eugenio
Published: November 2015

Analysis of civil structures at the scale of life‐cycle requires stochastic modeling of degradation. Phenomena causing structures to degrade are typically categorized as aging and point‐in‐time overloads. Earthquake effects are the members of the latter category this study deals with in the framework of performance‐based earthquake engineering (PBEE). The focus is structural seismic reliability, which requires modeling of the stochastic process describing damage progression, because of subsequent events, over time. The presented study explicitly addresses this issue via a Markov‐chain‐based approach, which is able to account for the change in seismic response of damaged structures (i.e. state‐dependent seismic fragility) as well as uncertainty in occurrence and intensity of earthquakes (i.e. seismic hazard). The state‐dependent vulnerability issue arises when the seismic hysteretic response is evolutionary and/or when the damage measure employed is such that the degradation increment probabilistically depends on the conditions of the structure at the time of the shock. The framework set up takes advantage also of the hypotheses of classical probabilistic seismic hazard analysis, allowing to separate the modeling of the process of occurrence of seismic shocks and the effect they produce on the structure. It is also discussed how the reliability assessment, which is in closed‐form, may be virtually extended to describe a generic age‐ and state‐dependent degradation process (e.g. including aging and/or when aftershock risk is of interest). Illustrative applications show the options to calibrate the model and its potential in the context of PBEE. Copyright © 2015 John Wiley & Sons, Ltd.
Prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents
Authors: Foley Kevin , Konetzka R. Tamara , Bunin Anthony , Yonan Charles
Published: November 2015

Objective

Pseudobulbar affect (PBA) is a neurological disorder of emotional expression, characterized by uncontrollable episodes of crying or laughing in patients with certain neurological disorders affecting the brain. The purposes of this study were to estimate the prevalence of PBA in US nursing home residents and examine the relationship between PBA symptoms and other clinical correlates, including the use of psychopharmacological medications.

Methods

A retrospective study was conducted between 2013 and 2014 with a convenience sample of residents from nine Michigan nursing homes. Chronic‐care residents were included in the “predisposed population” if they had a neurological disorder affecting the brain and no evidence of psychosis, delirium, or disruptive behavior (per chart review). Residents were screened for PBA symptoms by a geropsychologist using the Center for Neurologic Study‐Lability Scale (CNS‐LS). Additional clinical information was collected using a diagnostic evaluation checklist and the most recent Minimum Data Set 3.0 assessment.

Results

Of 811 residents screened, complete data were available for 804, and 412 (51%) met the criteria for the “predisposed population.” PBA symptom prevalence, based on having a CNS‐LS score ≥13, was 17.5% in the predisposed population and 9.0% among all nursing home residents. Those with PBA symptoms were more likely to have a documented mood disorder and be using a psychopharmacological medication, including antipsychotics, than those without PBA symptoms.

Conclusions

Pseudobulbar affect symptoms were present in 17.5% of nursing home residents with neurological conditions, and 9.0% of residents overall. Increasing awareness and improving diagnostic accuracy of PBA may help optimize treatment. © 2015 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.
Differences in neural activity when processing emotional arousal and valence in autism spectrum disorders
Authors: Tseng Angela , Wang Zhishun , Huo Yuankai , Goh Suzanne , Russell James A. , Peterson Bradley S.
Published: November 2015

Individuals with autism spectrum disorders (ASD) often have difficulty recognizing and interpreting facial expressions of emotion, which may impair their ability to navigate and communicate successfully in their social, interpersonal environments. Characterizing specific differences between individuals with ASD and their typically developing (TD) counterparts in the neural activity subserving their experience of emotional faces may provide distinct targets for ASD interventions. Thus we used functional magnetic resonance imaging (fMRI) and a parametric experimental design to identify brain regions in which neural activity correlated with ratings of arousal and valence for a broad range of emotional faces. Participants (51 ASD, 84 TD) were group‐matched by age, sex, IQ, race, and socioeconomic status. Using task‐related change in blood‐oxygen‐level‐dependent (BOLD) fMRI signal as a measure, and covarying for age, sex, FSIQ, and ADOS scores, we detected significant differences across diagnostic groups in the neural activity subserving the dimension of arousal but not valence. BOLD‐signal in TD participants correlated inversely with ratings of arousal in regions associated primarily with attentional functions, whereas BOLD‐signal in ASD participants correlated positively with arousal ratings in regions commonly associated with impulse control and default‐mode activity. Only minor differences were detected between groups in the BOLD signal correlates of valence ratings. Our findings provide unique insight into the emotional experiences of individuals with ASD. Although behavioral responses to face‐stimuli were comparable across diagnostic groups, the corresponding neural activity for our ASD and TD groups differed dramatically. The near absence of group differences for valence correlates and the presence of strong group differences for arousal correlates suggest that individuals with ASD are not atypical in all aspects of emotion‐processing. Studying these similarities and differences may help us to understand the origins of divergent interpersonal emotional experience in persons with ASD. Hum Brain Mapp 37:443–461, 2016. © 2015 Wiley Periodicals, Inc.
An empirical broad spectrum antibiotic therapy in health‐care–associated infections improves survival in patients with cirrhosis: A randomized trial
Authors: Merli Manuela , Lucidi Cristina , Di Gregorio Vincenza , Lattanzi Barbara , Giannelli Valerio , Giusto Michela , Farcomeni Alessio , Ceccarelli Giancarlo , Falcone Marco , Riggio Oliviero , Venditti Mario
Published: November 2015

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial because of their high morbidity and mortality. Multidrug‐resistant (MDR) infections are on the increase in health care settings. Health‐care–associated (HCA) infections are still frequently treated as community‐acquired with a detrimental effect on survival. We aimed to prospectively evaluate in a randomized trial the effectiveness of a broad spectrum antibiotic treatment in patients with cirrhosis with HCA infections. Consecutive patients with cirrhosis hospitalized with HCA infections were enrolled. After culture sampling, patients were promptly randomized to receive a standard or a broad spectrum antibiotic treatment (NCT01820026). The primary endpoint was in‐hospital mortality. Efficacy, side effects, and the length of hospitalization were considered. Treatment failure was followed by a change in antibiotic therapy. Ninety‐six patients were randomized and 94 were included. The two groups were similar for demographic, clinical, and microbiological characteristics. The prevalence of MDR pathogens was 40% in the standard versus 46% in the broad spectrum group. In‐hospital mortality showed a substantial reduction in the broad spectrum versus standard group (6% vs. 25%; P = 0.01). In a post‐hoc analysis, reduction of mortality was more evident in patients with sepsis. The broad spectrum showed a lower rate of treatment failure than the standard therapy (18% vs. 51%; P = 0.001). Length of hospitalization was shorter in the broad spectrum (12.3 ± 7 days) versus standard group (18 ± 15 days; P = 0.03). Five patients in each group developed a second infection during hospitalization with a similar prevalence of MDR (50% broad spectrum vs. 60% standard). Conclusions: A broad spectrum antibiotic therapy as empirical treatment in HCA infections improves survival in cirrhosis. This treatment was significantly effective, safe, and cost saving. (Hepatology 2016;63:1632‐1639)
Comparison of the accuracy of periodic reaction field methods in molecular dynamics simulations of a model liquid crystal system
Authors: Nozawa Takuma , Takahashi Kazuaki Z. , Narumi Tetsu , Yasuoka Kenji
Published: November 2015

A periodic reaction field (PRF) method is a technique to estimate long‐range interactions. The method has the potential to effectively reduce the computational cost while maintaining adequate accuracy. We performed molecular dynamics (MD) simulations of a model liquid‐crystal system to assess the accuracy of some variations of the PRF method in low‐charge‐density systems. All the methods had adequate accuracy compared with the results of the particle mesh Ewald (PME) method, except for a few simulation conditions. Furthermore, in all of the simulation conditions, one of the PRF methods had the same accuracy as the PME method. © 2015 Wiley Periodicals, Inc.
Inhibition of Polyamine Uptake Potentiates the Anti‐Proliferative Effect of Polyamine Synthesis Inhibition and Preserves the Contractile Phenotype of Vascular Smooth Muscle Cells
Authors: Grossi Mario , Phanstiel Otto , Rippe Catarina , Swärd Karl , Alajbegovic Azra , Albinsson Sebastian , Forte Amalia , Persson Lo , Hellstrand Per , Nilsson Bengt‐Olof
Published: November 2015

Increased vascular smooth muscle cell (VSMC) proliferation is a factor in atherosclerosis and injury‐induced arterial (re) stenosis. Inhibition of polyamine synthesis by α‐difluoro‐methylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, attenuates VSMC proliferation with high sensitivity and specificity. However, cells can escape polyamine synthesis blockade by importing polyamines from the environment. To address this issue, polyamine transport inhibitors (PTIs) have been developed. We investigated the effects of the novel trimer44NMe (PTI‐1) alone and in combination with DFMO on VSMC polyamine uptake, proliferation and phenotype regulation. PTI‐1 efficiently inhibited polyamine uptake in primary mouse aortic and human coronary VSMCs in the absence as well as in the presence of DFMO. Interestingly, culture with DFMO for 2 days substantially (>95%) reduced putrescine (Put) and spermidine (Spd) contents without any effect on proliferation. Culture with PTI‐1 alone had no effect on either polyamine levels or proliferation rate, but the combination of both treatments reduced Put and Spd levels below the detection limit and inhibited proliferation. Treatment with DFMO for a longer time period (4 days) reduced Put and Spd below their detection limits and reduced proliferation, showing that only a small pool of polyamines is needed to sustain VSMC proliferation. Inhibited proliferation by polyamine depletion was associated with maintained expression of contractile smooth marker genes. In cultured intact mouse aorta, PTI‐1 potentiated the DFMO‐induced inhibition of cell proliferation. The combination of endogenous polyamine synthesis inhibition with uptake blockade is thus a viable approach for targeting unwanted vascular cell proliferation in vivo, including vascular restenosis. J. Cell. Physiol. 231: 1334–1342, 2016. © 2015 Wiley Periodicals, Inc.
Radiosynthesis and ‘click’ conjugation of ethynyl‐4‐[18F]fluorobenzene — an improved [18F]synthon for indirect radiolabeling
Authors: Roberts Maxine P. , Pham Tien Q. , Doan John , Jiang Cathy D. , Hambley Trevor W. , Greguric Ivan , Fraser Benjamin H.
Published: November 2015

Reproducible methods for [18F]radiolabeling of biological vectors are essential for the development of new [18F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi‐step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [18F]radiolabeling of such molecules, our group has synthesized ethynyl‐4‐[18F]fluorobenzene ([18F]2, [18F]EYFB) in a single step (14 ± 2% non‐decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne‐functionalized synthon [18F]2 was then conjugated to two azido‐functionalized vector molecules via CuAAC reactions. The first ‘proof of principle’ conjugation of [18F]2 to 1‐azido‐1‐deoxy‐β‐d‐glucopyranoside (3) gave the desired radiolabeled product [18F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [18F]2 to matrix‐metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [18F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [18F]4 and [18F]6 including [18F]F− drying, two‐step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [18F]2 and the conjugated products, [18F]4 and [18F]6, were all greater than 98%. The specific activities of [18F]2 and [18F]6 were low, 5.97 and 0.17 MBq nmol−1, respectively.
Efficient and facile synthesis of novel stable monodeuterium labeled ractopamine
Authors: Su Feifei , Wu Fulong , Tang He , Wang Zhonghua , Wu Fanhong
Published: November 2015

A novel synthetic route to stable deuterium labeled ractopamine was disclosed with 6.49% total yield and 97.7% isotopic abundance. Its structure and the isotope‐abundance were confirmed according to 1H‐NMR and high‐resolution mass spectrometry.
Minocycline mitigates the gliogenic effects of proinflammatory cytokines on neural stem cells
Authors: Vay Sabine Ulrike , Blaschke Stefan , Klein Rebecca , Fink Gereon Rudolf , Schroeter Michael , Rueger Maria Adele
Published: November 2015

Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor‐α, interleukin 1β, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine‐induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways. © 2015 Wiley Periodicals, Inc.
Aggregation of egg white proteins with pulsed electric fields and thermal processes
Authors: Wu Li , Zhao Wei , Yang Ruijin , Yan Wenxu , Sun Qianyan
Published: November 2015

BACKGROUND

Pulsed electric field (PEF) processing is progressing towards application for liquid egg to ensure microbial safety. However, it usually causes protein aggregation, and the mechanism is still unclear. In this study, egg white protein was applied to investigate the changes in protein structure and mechanism of aggregates formation and a comparison was made with thermal treatment.

RESULTS

Soluble protein content decreased with the increase of turbidity after both treatments. Fluorescence intensity and free sulfhydryl content were increased after being treated at 70 °C for 4 min. Less‐remarkable changes of hydrophobicity were observed after PEF treatments (30 kV cm−1, 800 µs). Soluble and insoluble aggregates were observed by thermal treatment, and disulfide bonds were the main binding forces. The main components of insoluble aggregates formed by thermal treatment were ovotransferrin (30.58%), lysozyme (18.47%) and ovalbumin (14.20%). While only insoluble aggregates were detected during PEF processes, which consists of ovotransferrin (11.86%), lysozyme (21.11%) and ovalbumin (31.07%). Electrostatic interaction played a very important role in the aggregates formation.

CONCLUSION

PEF had a minor impact on the structure of egg white protein. PEF had insignificant influence on heat‐sensitive protein, indicating that PEF has potential in processing food with high biological activity and heat sensitive properties. © 2015 Society of Chemical Industry
Functional outcome after Ivor Lewis esophagectomy for cancer
Authors: Deldycke Annelies , Van Daele Elke , Ceelen Wim , Van Nieuwenhove Yves , Pattyn Piet
Published: November 2015

Background

Little is known on functional outcome after Ivor Lewis esophagectomy (ILE) with intrathoracic anastomosis.

Methods

Patients who underwent ILE were identified from a prospective database. Clinicopathological data were retrieved and compared with functional outcome data based on patient self‐assessment by a standard questionnaire. Predictive factors for selected functional complaints were identified with logistic regression analyses.

Results

Three hundred and twenty‐two patients (80.4% male, mean age 62 years) were studied. Indications for surgery were adenocarcinoma (62.4%), squamous cell carcinoma (28%), and HG Barrett dysplasia (7%). Preoperative chemoradiation (CRT) was administered to 42.5% of patients. Anastomotic leakage occurred in 5.6% and was associated with higher age and diabetes mellitus. Functional symptoms identified were reflux (39%), delayed gastric emptying (37%), dumping (21.4%), and anastomotic stenosis (16%). In the multivariate models, anastomotic stenosis was associated with smaller stapler diameter and presence of esophagitis. Postoperative reflux was associated with higher BMI, whereas dumping was predicted by female gender and age. The quality of life questionnaires revealed a good general health status in 82% of the patients.

Conclusions

Functional complaints after ILE consist of reflux, delayed gastric emptying, dumping, and dysphagia, and are affected by age, gender, BMI, diabetes mellitus, and stapler diameter. J. Surg. Oncol. 2016;113:24–28. © 2015 Wiley Periodicals, Inc.
Severe bradycardia associated with suspension laryngoscopy
Authors: Latuska Richard F. , Kuhl Nicholas O. , Garrett C. Gaelyn , Berry James M. , Gelbard Alexander
Published: November 2015

Suspension laryngoscopy is one of the most common procedures performed for visualizing and diagnosing diseases of the larynx. A relatively uncommon yet potentially life‐threatening complication is that of severe bradycardia or asystole during manipulation of the larynx. This case report highlights the occurrence of this complication during a routine removal of a true vocal fold lesion at a tertiary medical center and discusses the potential pathophysiological mechanisms and proposed management options for this phenomenon. Laryngoscope, 126:949–950, 2016
Using Lean Thinking at an otorhinolaryngology outpatient clinic to improve quality of care
Authors: van Leijen‐Zeelenberg Janneke E. , Brunings Jan Wouter , Houkes Inge , van Raak Arno J. A. , Ruwaard Dirk , Vrijhoef Hubertus J. M. , Kremer Bernd
Published: November 2015

Objectives/Hypothesis

Although Lean Thinking has led to considerable improvement in a variety of healthcare settings, its effects on otorhinolaryngology remain underexposed. This study reports on how the implementation of Lean Thinking at an otorhinolaryngology outpatient clinic has affected patient and provider satisfaction, waste reduction, and organizational culture.

Study Design

Prospective before‐and‐after design.

Methods

The 18‐month prospective before‐and‐after design used mixed methods for data collection and analysis. A survey was conducted to measure satisfaction among patients and providers. Semistructured interviews were conducted to evaluate the effect of Lean Thinking on waste and organizational culture.

Results

During the project, 69 issues were posted on the Lean board. Improvements were made on 36 inefficiency issues, not all concerning a specific type of waste. Employees reported considerable improvement in transportation, motion, and waiting. Patient satisfaction was high both at baseline and follow‐up and did not change significantly. The effects on provider satisfaction were slight; satisfaction with autonomy and participation decreased significantly, but satisfaction with communication increased significantly.

Conclusions

The implementation of Lean Thinking at an otorhinolaryngology outpatient clinic reduced waste and increased provider satisfaction with communication. Although patient satisfaction did not change significantly, it cannot be concluded that the intervention had no effect on perceived quality of care. Other approaches to measure patients' perceptions should be considered.

Level of Evidence

NA Laryngoscope, 126:839–846, 2016
Endolymphatic hydrops in superior canal dehiscence and large vestibular aqueduct syndromes
Authors: Sone Michihiko , Yoshida Tadao , Morimoto Kyoko , Teranishi Masaaki , Nakashima Tsutomu , Naganawa Shinji
Published: November 2015

Objectives/Hypothesis

Pathologic third window lesions, such as superior semicircular canal dehiscence syndrome (SCDS) or large vestibular aqueduct syndrome (LVAS), cause several auditory and vestibular symptoms, which might affect perilymphatic pressure and induce endolymphatic hydrops (EH). In this study, the existence of EH in subjects with SCDS or LVAS was investigated using contrast‐enhanced magnetic resonance imaging (MRI).

Study Design

Case series at university hospital.

Methods

Seventeen ears from nine subjects who were diagnosed as having SCDS (five ears from three cases) or LVAS (12 ears from six cases) were studied. Ears were evaluated by 3‐T MRI performed 4 hours after intravenous injection of gadodiamide hydrate. Imaging data concerning the degree of EH in the cochlea and the vestibule were compared with clinical symptoms and hearing levels for all ears.

Results

All ears showed air–bone gaps at low frequencies on pure tone audiometry. None of the subjects with SCDS had episodes of acute sensorineural hearing loss (SNHL) or vestibular symptoms, except for one patient who complained of head vibration induced by loud noise. Conversely, five of six subjects with LVAS had episodes of acute SNHL or vestibular symptoms. Four of five ears with SCDS showed severe EH in the cochlea, and two ears showed mild EH in the vestibule. All ears with LVAS showed mild to severe EH in both the cochlea and vestibule.

Conclusions

The present study demonstrated the existence of EH in ears with pathologic third window lesions, which might affect patients' auditory or vestibular symptoms.

Level of Evidence

4 Laryngoscope, 126:1446–1450, 2016
Comprehensive application of robotic retroauricular thyroidectomy: The evolution of robotic thyroidectomy
Authors: Byeon Hyung Kwon , Kim Da Hee , Chang Jae Won , Ban Myung Jin , Park Jae Hong , Kim Won Shik , Choi Eun Chang , Koh Yoon Woo
Published: November 2015

Objectives/Hypothesis

As an evolvement of the robotic application to the thyroidectomy, we sought to seek the potential role of robotic thyroidectomy with the retroauricular (RA) approach prior to future comparative study between RA and transaxillary thyroidectomy. This study aims to verify the surgical feasibility of robotic RA thyroidectomy.

Study Design

Case series with planned data collection.

Methods

A total of 87 patients who underwent robotic RA thyroidectomy for clinically suspicious papillary thyroid carcinoma or benign lesions from January 2013 to May 2014 were retrospectively reviewed and analyzed.

Results

All robotic surgeries via RA approach were successfully performed, without any significant intraoperative complications or conversion to open surgery. Based on patient‐reported outcome questionnaires, all patients were satisfied with their postoperative surgical scars.

Conclusion

Robotic RA thyroidectomy is technically feasible and safe, with satisfactory cosmetic results for patients where indicated.

Level of Evidence

4. Laryngoscope, 126:1952–1957, 2016
Geographic trends in management of early‐stage laryngeal cancer
Authors: Mourad Moustafa , Dezube Aaron , Moshier Erin , Shin Edward
Published: November 2015

Objectives/Hypothesis

The goal of the study was to identify geographic trends in the primary treatment of early‐stage glottic cancer.

Study Design

Retrospective analysis of the United States National Cancer Institute's Surveillance, Epidemiology, and End‐Results (SEER) database.

Methods

Using the most up‐to‐date November 2014 submission of the SEER database in addition to SEER‐18 data files, a cohort was created of stage I to II squamous cell glottic cancer from 2004 to 2012. The treatment groups (radiation and surgery) were compared with respect to several pretreatment covariates including age, race, gender, state where they received treatment, year of diagnosis, and American Joint Committee on Cancer (AJCC) stage.

Results

In analyzing geographic trends, a statistically significant difference in treatment received by region and state was found (P < .0001.). When examining patient demographics, there was no statistically significant difference in treatment by age (P = .5206), AJCC stage (P = .4922), or year of diagnosis (P = .6593). There was a significant difference in racial distribution by treatment (P = .0038), with patients receiving surgery more likely to be black than patients receiving radiation (12% vs. 10%). In analyzing overall survival (OS), there was no significant difference in OS among the four US treatment regions (P = .2508).

Conclusions

Geographic factors impact overall treatment of early‐stage glottic cancer. In addition, it was determined that race was a factor that correlated to differences in treatment modality. Finally, overall survival across the United States was determined to be significantly better in patients receiving radiation therapy.

Level of Evidence

4 Laryngoscope, 126:880–884, 2016
Long‐Term Durum Wheat‐Based Cropping Systems Result in the Rapid Saturation of Soil Carbon in the Mediterranean Semi‐arid Environment
Authors: Novara Agata , Poma Ignazio , Sarno Mauro , Venezia Giacomo , Gristina Luciano
Published: November 2015

Climate, soil physical–chemical characteristics, land management, and carbon (C) input from crop residues greatly affect soil organic carbon (SOC) sequestration. According to the concept of SOC saturation, the ability of SOC to increase with C input decreases as SOC increases and approaches a SOC saturation level. In a 12‐year experiment, six semi‐arid cropping systems characterized by different rates of C input to soil were compared for ability to sequester SOC, SOC saturation level, and the time necessary to reach the SOC saturation level. SOC stocks, soil aggregate sizes, and C inputs were measured in durum wheat monocropping with (Ws) and without (W) return of aboveground residue to the soil and in the following cropping systems without return of aboveground residue to soil: durum wheat/fallow (Wfall), durum wheat/berseem clover, durum wheat/barley/faba bean, and durum wheat/Hedysarum coronarium. The C sequestration rate and SOC content were lowest in Wfall plots but did not differ among the other cropping systems. The C sequestration rate ranged from 0.47 Mg C ha−1 y−1 in Ws plots to 0.66 Mg C ha−1 y−1 in W plots but was negative (−0.06 Mg C ha−1 y−1) in Wfall plots. Increases in SOC were related to C input up to a SOC saturation value; over this value, further C inputs did not lead to SOC increase. Across all cropping systems, the C saturation value for the experimental soil was 57.7 Mg ha−1, which was reached with a cumulative C input of 15 Mg ha−1. Copyright © 2015 John Wiley & Sons, Ltd.
Volumetric changes in transplanted vascularized fat flaps after ischemic or congestive stresses and their relationship to capillary density in a zucker fatty rat model
Authors: Tanaka Kentaro , Okazaki Mutsumi , Yano Tomoyuki , Akiyama Masako , Mori Hiroki , Uemura Noriko
Published: November 2015

Background

The aim of this study was to examine volumetric changes in fat flaps after stresses as well as their relationship with capillary density (CD) in a Zucker fatty rat model.

Methods

A total of 12 male Zucker‐fa/fa rats were randomly divided into two stress groups. Superficial epigastric fat flaps were evaluated on the right side as control and on the left side as the stress (ischemic or congestive) condition in the same rat in order to avoid biases. Stress conditions were made by obstructing the pedicle vessels with a vascular clip for 3 hours. The volumes of these flaps were measured weekly. After 12 weeks of measurements, the CD of harvested flaps was examined in histologically immunostained sections. Percent changes in the body‐weight‐corrected flap volume [cFV(%)], the stress/control ratio [FV‐ratio(%)], and the stress/control ratio of CD (CD‐ratio) were defined.

Results

cFV(%) 12 weeks after surgery was 34.7 ± 26.7 in the control flaps and 13.2 ± 10.5 in the stress flaps. The FV‐ratio(%) after 12 weeks was 7.4–202.5 (70.2 ± 77.9) in the ischemic group and 14.6–66.3 (37.7 ± 22.2) in the congestive group. The difference in variance between two groups was significant (P = 0.030). cFV(%) correlated with total CD (P = 0.011). The FV‐ratio(%) correlated with the CD‐ratio (P = 0.002).

Conclusions

Weekly measurements of flap volumes in the Zucker fatty rat model were new and useful methods. The FV‐ratio(%) in the congestive group decreased at a constant rate, while that in the ischemic group decreased or increased slightly. The rate of decreases in the flap volume correlated with CD. © 2015 Wiley Periodicals, Inc. Microsurgery 35:653–661, 2015.
Fast three‐dimensional inner volume excitations using parallel transmission and optimized k‐space trajectories
Authors: Davids Mathias , Schad Lothar R. , Wald Lawrence L. , Guérin Bastien
Published: November 2015

Purpose

To design short parallel transmission (pTx) pulses for excitation of arbitrary three‐dimensional (3D) magnetization patterns.

Methods

We propose a joint optimization of the pTx radiofrequency (RF) and gradient waveforms for excitation of arbitrary 3D magnetization patterns. Our optimization of the gradient waveforms is based on the parameterization of k‐space trajectories (3D shells, stack‐of‐spirals, and cross) using a small number of shape parameters that are well‐suited for optimization. The resulting trajectories are smooth and sample k‐space efficiently with few turns while using the gradient system at maximum performance. Within each iteration of the k‐space trajectory optimization, we solve a small tip angle least‐squares RF pulse design problem. Our RF pulse optimization framework was evaluated both in Bloch simulations and experiments on a 7T scanner with eight transmit channels.

Results

Using an optimized 3D cross (shells) trajectory, we were able to excite a cube shape (brain shape) with 3.4% (6.2%) normalized root‐mean‐square error in less than 5 ms using eight pTx channels and a clinical gradient system (Gmax = 40 mT/m, Smax = 150 T/m/s). This compared with 4.7% (41.2%) error for the unoptimized 3D cross (shells) trajectory. Incorporation of B0 robustness in the pulse design significantly altered the k‐space trajectory solutions.

Conclusion

Our joint gradient and RF optimization approach yields excellent excitation of 3D cube and brain shapes in less than 5 ms, which can be used for reduced field of view imaging and fat suppression in spectroscopy by excitation of the brain only. Magn Reson Med 76:1170–1182, 2016. © 2015 Wiley Periodicals, Inc.